Isolated prolapse of the posterior mitral valve leaflet: phenotypic refinement, heritability and genetic etiology.

BACKGROUND: Isolated posterior leaflet mitral valve prolapse (PostMVP), a common form of MVP, often referred as fibroelastic deficiency, is considered a degenerative disease. PostMVP patients are usually asymptomatic and often undiagnosed until chordal rupture. The present study aims to characterize familial PostMVP phenotype and familial recurrence, its genetic background, and the pathophysiological processes involved. METHODS: We prospectively enrolled 284 unrelated MVP probands, of whom 178 (63%) had bi-leaflet MVP and 106 had PostMVP (37%). Familial screening within PostMVP patients allowed the identification of 20 families with inherited forms of PostMVP for whom whole genome sequencing was carried out in probands. Functional in vivo and in vitro investigations were performed in zebrafishand in Hek293T cells. RESULTS: In the 20 families with inherited form of PostMVP, 38.8% of relatives had a MVP/prodromal form, mainly of the posterior leaflet, with transmission consistent with an autosomal dominant mode of inheritance. Compared with control relatives, PostMVP family patients have clear posterior leaflet dystrophy on echocardiography. Patients with PostMVP present a burden of rare genetic variants in ARHGAP24. ARHGAP24 encodes the filamin A binding RhoGTPase-activating protein FilGAP and its silencing in zebrafish leads to atrioventricular regurgitation. In vitro functional studies showed that variants of FilGAP, found in PostMVP families, are loss-of-function variants impairing cellular adhesion and mechano-transduction capacities. CONCLUSIONS: PostMVP should not only be considered an isolated degenerative pathology but as a specific heritable phenotypic trait with genetic and functional pathophysiological origins. The identification of loss-of-function variants in ARHGAP24 further reinforces the pivotal role of mechano-transduction pathways in the pathogenesis of MVP. CLINICAL PERSPECTIVE: Isolated posterior mitral valve prolapse (PostMVP), often called fibro-elastic deficiency MVP, is at least in some patients, a specific inherited phenotypic traitPostMVP has both genetic and functional pathophysiological origins Genetic variants in the ARHGAP24 gene, which encodes for the FilGAP protein, cause progressive Post MVP in familial cases, and impair cell adhesion and mechano-transduction capacities.

Haemoadsorption in infective endocarditis: a systematic review.

Infective endocarditis surgical patients suffer from high rates of severe complications such as systemic inflammatory response, septic shock, and multi-organ failure leading to high mortality. Systemic inflammatory response based on cytokines as messengers plays an important role in these patients. The concept of intraoperative haemoadsorption has been proposed to remove such elevated cytokines in patients undergoing cardiac surgery for infective endocarditis. Haemoadsorption offers the possibility to stabilise haemodynamics, reduce sepsis-related mortality, and protect organ function. However, until now, there has been no general opinion and consensus regarding the clinical effectiveness of adjunctive intraoperative haemoadsorption in infective endocarditis. Therefore, we reviewed the current literature evaluating haemoadsorption in infective endocarditis patients undergoing cardiac surgery. The review was registered at PROSPERO (CRD42023457632). Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-024-01701-0.

The role of hemoadsorption in cardiac surgery - a systematic review.

BACKGROUND: Extracorporeal blood purification has been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with the emergence of new adsorptive blood purification devices, hemoadsorption has been increasingly applied during CPB in cardiac surgery, for patients at different inflammatory risks, or for postoperative complications. Clinical evidence so far has not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to critically assess the role of perioperative hemoadsorption in cardiac surgery, by summarizing the current knowledge in this clinical setting. METHODS: A literature search of PubMed, Cochrane library, and the database provided by CytoSorbents was conducted on June 1st, 2023. The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search, including language variations of terms "cardiac surgery" and "hemoadsorption". The screening and selection process followed scientific principles (PRISMA statement). Abstracts were considered for inclusion if they were written in English and published within the last ten years. Publications were eligible for assessment if reporting on original data from any type of study (excluding case reports) in which a hemoadsorption device was investigated during or after cardiac surgery. Results were summarized according to sub-fields and presented in a tabular view. RESULTS: The search resulted in 29 publications with a total of 1,057 patients who were treated with hemoadsorption and 988 control patients. Articles were grouped and descriptively analyzed due to the remarkable variability in study designs, however, all reported exclusively on CytoSorb® therapy. A total of 62% (18/29) of the included articles reported on safety and no unanticipated adverse events have been observed. The most frequently reported clinical outcome associated with hemoadsorption was reduced vasopressor demand resulting in better hemodynamic stability. CONCLUSIONS: The role of hemoadsorption in cardiac surgery seems to be justified in selected high-risk cases in infective endocarditis, aortic surgery, heart transplantation, and emergency surgery in patients under antithrombotic therapy, as well as in those who develop a dysregulated inflammatory response, vasoplegia, or septic shock postoperatively. Future large randomized controlled trials are needed to better define proper patient selection, dosing, and timing of the therapy.

Effects of high-intensity inspiratory muscle training on systemic inflammatory response in cardiac surgery - A randomized clinical trial.

PURPOSE: Preoperative inspiratory muscle training reduces the incidence of postoperative pulmonary complications after cardiac surgery, but training protocols vary widely in terms of intensity. Currently, the mechanisms underlying the effectiveness of this practice are not known. The purpose of the present study is to determine whether preoperative high-intensity inspiratory muscle training (HI-IMT) modulates the perioperative systemic inflammatory response in cardiac surgery patients. METHODS: Participants awaiting surgical aortic valve replacement were randomized to 3 to 6 weeks preoperative home-based HI-IMT or same duration low-intensity inspiratory muscle training (LI-IMT). The primary outcome was the preoperative value of the soluble tumor necrosis factor receptor 1 (sTNFR1). Secondary outcomes assessed perioperative evolution of the cytokines: sTNFR1, Tumor necrosis factor-α, Interleukin (IL)-6, IL-8, IL10, IL1ß, and their combined z-score; reflecting post-training and postoperative inflammatory response. Perioperative pulmonary function and postoperative clinical outcomes were collected. RESULTS: Between February 2018 and March 30, 2019 patients were randomized, to HI-IMT or LI-IMT. There were no differences between the groups in terms of baseline characteristics. The median (IQR) training duration was 34 (28-44) days. After training, the median (IQR) predicted maximal inspiratory pressure was higher in the HI-IMT vs LI-IMT group (119 (96-142%) vs 97 (81-107%); p = .04) Levels of the sTNFR1 cytokine increased during training in the HI-IMT group, pre vs post training (Median (IQR) 1073 (920; 1219) vs 1172 (965; 1368) ng/L; p = .03). The 24-h postoperative global inflammatory score was lower in the HI-IMT than in the LI-IMT group (Median (IQR), -0.37 (-0.62, 0.03) vs -0.10 (-0.17, 0.49), p = .04). Global inflammatory scores were not different at other time points. There were no significant differences between the groups in post-operative pulmonary function and postoperative clinical outcome. CONCLUSION: High intensity inspiratory muscle training shows immunomodulatory properties. These properties could explain why preoperative inspiratory muscle training can lead to lung protection after cardiac surgery.

2021 MiECTiS focused update on the 2016 position paper for the use of minimal invasive extracorporeal circulation in cardiac surgery.

The landmark 2016 Minimal Invasive Extracorporeal Technologies International Society (MiECTiS) position paper promoted the creation of a common language between cardiac surgeons, anesthesiologists and perfusionists which led to the development of a stable framework that paved the way for the advancement of minimal invasive perfusion and related technologies. The current expert consensus document offers an update in areas for which new evidence has emerged. In the light of published literature, modular minimal invasive extracorporeal circulation (MiECC) has been established as a safe and effective perfusion technique that increases biocompatibility and ultimately ensures perfusion safety in all adult cardiac surgical procedures, including re-operations, aortic arch and emergency surgery. Moreover, it was recognized that incorporation of MiECC strategies advances minimal invasive cardiac surgery (MICS) by combining reduced surgical trauma with minimal physiologic derangements. Minimal Invasive Extracorporeal Technologies International Society considers MiECC as a physiologically-based multidisciplinary strategy for performing cardiac surgery that is associated with significant evidence-based clinical benefit that has accrued over the years. Widespread adoption of this technology is thus strongly advocated to obtain additional healthcare benefit while advancing patient care.

AORTLANTIC: French registry of aortic valve-sparing root replacement, preliminary multicentre results from western France.

OBJECTIVES: Aortic root aneurysms often affect younger patients in whom valve-sparing surgery is challenging. Among current techniques, aortic valve-sparing root replacement described by Tirone David has shown encouraging results. The AORTLANTIC registry was instituted for a multicentre long-term evaluation of this procedure. The current initial study evaluates the hospital outcomes of the procedure. METHODS: This is a retrospective study of patients operated between 1 January 2004 and 31 December 2020 in 6 hospitals in western France. All study data were recorded in the national digital database of the French Society of Cardiac Surgery: EPICARD. RESULTS: A total of 524 consecutive patients with a mean age of 53 (15.1) years underwent surgery. 13% (n = 68) of patients presented with acute aortic dissection, 16.5% (n = 86) had associated connective tissue pathology and 7.3% (n = 37) had bicuspid aortic valves. Preoperative aortic regurgitation (AR) ≥2/4 was present in 65.3% (n = 341) of patients. Aortic valvuloplasty was required in 18.6% (n = 95) of patients. At discharge, 92.8% (n = 461) of patients had no or 1/4 AR. The stroke rate was 1.9% (n = 10). Intra-hospital mortality was 1.9% (n = 10). CONCLUSIONS: The AORTLANTIC registry includes 6 centres in western France with >500 patients. Despite numerous complex cases (acute aortic dissections, bicuspid aortic valves, preoperative AR), aortic valve-sparing root replacement has a low intra-hospital mortality. The initial encouraging results of this multicentre study warrant further long-term evaluation by future studies.

Guidelines on enhanced recovery after cardiac surgery under cardiopulmonary bypass or off-pump.

OBJECTIVE: To provide recommendations for enhanced recovery after cardiac surgery (ERACS) based on a multimodal perioperative medicine approach in adult cardiac surgery patients with the aim of improving patient satisfaction, reducing postoperative mortality and morbidity, and reducing the length of hospital stay. DESIGN: A consensus committee of 20 experts from the French Society of Anaesthesia and Intensive Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and the French Society of Thoracic and Cardiovascular Surgery (Société française de chirurgie thoracique et cardio-vasculaire, SFCTCV) was convened. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. The entire guideline process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide the assessment of the quality of evidence. METHODS: Six fields were defined: (1) selection of the patient pathway and its information; (2) preoperative management and rehabilitation; (3) anaesthesia and analgesia for cardiac surgery; (4) surgical strategy for cardiac surgery and bypass management; (5) patient blood management; and (6) postoperative enhanced recovery. For each field, the objective of the recommendations was to answer questions formulated according to the PICO model (Population, Intervention, Comparison, Outcome). Based on these questions, an extensive bibliographic search was carried out and analyses were performed using the GRADE approach. The recommendations were formulated according to the GRADE methodology and then voted on by all the experts according to the GRADE grid method. RESULTS: The SFAR/SFCTCV guideline panel provided 33 recommendations on the management of patients undergoing cardiac surgery under cardiopulmonary bypass or off-pump. After three rounds of voting and several amendments, a strong agreement was reached for the 33 recommendations. Of these recommendations, 10 have a high level of evidence (7 GRADE 1+ and 3 GRADE 1-); 19 have a moderate level of evidence (15 GRADE 2+ and 4 GRADE 2-); and 4 are expert opinions. Finally, no recommendations were provided for 3 questions. CONCLUSIONS: Strong agreement existed among the experts to provide recommendations to optimise the complete perioperative management of patients undergoing cardiac surgery.

Heritability of aortic valve stenosis and bicuspid enrichment in families with aortic valve stenosis.

BACKGROUND: Although a familial component of calcific aortic valve stenosis (CAVS) has been described, its heritability remains unknown. Hence, we aim to assess the heritability of CAVS and the prevalence of bicuspid aortic valve among CAVS families. METHODS: Probands were recruited following aortic valve replacement (AVR) for severe CAVS on either tricuspid (TAV) or bicuspid aortic valve (BAV). After screening, relatives underwent a Doppler-echocardiography to assess the aortic valve morphology as well as the presence and severity of CAVS. Families were classified in two types according to proband's aortic valve phenotype: TAV or BAV families. Control families were recruited and screened for the presence of BAV. RESULTS: Among the 2371 relatives from 138 CAVS families (pedigree cohort), heritability of CAVS was significant (h2 = 0.47, p < 0.0001), in TAV (h2 = 0.49, p < 0.0001) and BAV families (h2 = 0.50, p < 0.0001). The prevalence of BAV in 790 relatives (phenotype cohort) was significantly increased in both TAV and BAV families compared to control families with a prevalence ratio of 2.6 ([95%CI:1.4-5.9]; p = 0.005) and 4.6 ([95%CI:2.4-13.4]; p < 0.0001), respectively. At least one relative had a BAV in 22.2% of tricuspid CAVS families. CONCLUSIONS: Our study confirms the heritability of CAVS in both TAV and BAV families, suggesting a genetic background of this frequent valvular disease. In addition, BAV enrichment in TAV families suggests an interplay between tricuspid CAVS and BAV. Overall results support the need to improve phenotyping (i.e. BAV, TAV, risk factors) in CAVS families in order to enhance the identification of rare and causal genetic variants of CAVS. CLINICAL TRIALS IDENTIFIER: NCT02890407.

Preservation of the Aortic Root During Type A Aortic Dissection Surgery: An Effective Strategy?

BACKGROUND: Management of the aortic root during acute Type A aortic dissection (TAAD) repair remains controversial in term of long-term evolution and reoperation. The aim of this study was to assess the long-term outcomes of the aortic root after conservative management during primary surgery. METHODS: One hundred sixty-four consecutive patients were included in this monocentric retrospective study. The primary endpoint was reoperation on the aortic root during long-term follow-up. Forty-six patients had aortic root replacement (ARR) and 118 had supracoronary aortic replacement (SCR). The 10-year survival, occurrence of significant aortic regurgitation, and radiologic aortic root dilatation in each group were assessed during follow-up. RESULTS: Patients from ARR group were younger than those from SCR group (p < 0.0001). Median follow-ups of ARR group and SCR group are 4.4 (interquartile range [IR]: 2.6-8.3) and 6.15 (IR: 2.8-10.53) years, respectively. Reoperation of the aortic root during long-term follow-up was similar in both groups (ARR group: 5.1%, SCR group: 3.3%, p = 0.636). The 10-year survivals of ARR and SCR groups were 64.8 ± 12.3% and 46.3 ± 5.8% (p = 0.012), respectively. Long-term significant aortic regurgitation occurred in one patient (1.7%) and seven patients (7.6%) of the ARR and SCR groups (p = 0.176), respectively. Radiologic aortic root diameters in the SCR group were similar between postoperative period and follow-up studies (p = 0.58). Reoperation on the distal aorta (p = 0.012) and patent radiologic false lumen of the descending aorta (p = 0.043) were independent risk factors of late death. CONCLUSION: SCR is an effective technique for primary TAAD surgery and does not increase the rate of late reoperation on the aortic root.

STABILISE Technique via a Transapical Approach to Repair Residual Type A Aortic Dissection.

The stent-assisted balloon-induced intimal disruption and relamination in aortic dissection or STABILISE concept is a novel endovascular strategy in Type A and Type B dissections. We report a case of Type A aortic dissection repair combining, first, an open thoracic aortic surgery with an elephant trunk procedure and, second, an endovascular treatment using the STABILISE technique via a combined transapical approach commonly used for transcatheter aortic valve implantation and a femoral pathway.

Aortic homograft for aortic valve replacement in patient with Alpha-Gal allergy.

Allergy to Galactose-Alpha-1,3-Galactose is an allergy to mammalian proteins, that are present on the surface of standard bioprosthestic valves, and could result in a catastrophic allergic reaction or may cause early deterioration of the bioprostheses. Aortic homograft is an acceptable alternative to standard prosthetic valves (biological and mechanical) to avoid a potential allergic manifestation and the need for definitive oral anticoagulation. We report the implantation of an aortic homograft in a patient with an aortic stenosis who presents a documented AlphaGal allergy.

Extracorporeal circulation during on-pump cardiac surgery: An evaluation of the energy equivalent pressure index based on waveforms decomposition in harmonics.

The use of pulsatile perfusion instead of nonpulsatile perfusion during cardiopulmonary bypass continues to be a source of debate. The disagreements among the conclusions of the published studies may be due to different factors: differences in the type of patients included in the studies, differences in the protocol of the studies, and difficulty to quantify the pulsatility of the flow. In the present paper, we propose a quantitative evaluation of Shepard's energy equivalent pressure index, based on the harmonic decomposition of the physiological aortic pressure and flow rate signal. It is thus demonstrated that the surplus energy provided by pulsatile flow remains moderate (of order 10 mm Hg), but that it can be improved by changing the relative shapes of the pressure and flow waves.

Author's reply (in reference to letter to editor proposed by Etem Caliskan, Catherine J. Pachuk, Louis P. Perrault, Maximilian Y Emmert and entitled: preservation solutions to improve graft patency: The devil is in the detail).

Not applicable.

Preoperative endothelial dysfunction in cutaneous microcirculation is associated with postoperative organ injury after cardiac surgery using extracorporeal circulation: a prospective cohort study.

BACKGROUND: Cardiac surgery is known to induce acute endothelial dysfunction, which may be central to the pathophysiology of postoperative complications. Preoperative endothelial dysfunction could also be implicated in the pathophysiology of postoperative complications after cardiac surgery. However, the relationship between preoperative endothelial function and postoperative outcomes remains unknown. The primary objective was to describe the relationship between a preoperative microcirculatory dysfunction identified by iontophoresis of acetylcholine (ACh), and postoperative organ injury in patients scheduled for cardiac surgery using cardiopulmonary bypass (CPB). METHODS: Sixty patients undergoing elective cardiac surgery using CPB were included in the analysis of a prospective, observational, single-center cohort study conducted from January to April 2019. Preoperative microcirculation was assessed with reactivity tests on the forearm (iontophoresis of ACh and nitroprusside). Skin blood flow was measured by laser speckle contrast imaging. Postoperative organ injury, the primary outcome, was defined as a Sequential Organ Failure Assessment score (SOFA) 48 h after surgery greater than 3. RESULTS: Organ injury at 48 h occurred in 29 cases (48.3%). Patients with postoperative organ injury (SOFA score > 3 at 48 h) had a longer time to reach the peak of preoperative iontophoresis of acetylcholine (133 s [104-156] vs 98 s [76-139] than patients without, P = 0.016), whereas endothelium-independent vasodilation to nitroprusside was similar in both groups. Beyond the proposed threshold of 105 s for time to reach the peak of preoperative endothelium-dependent vasodilation, three times more patients presented organ dysfunction at 48 h (76% vs 24% below or equal 105 s). In multivariable model, the time to reach the peak during iontophoresis of acetylcholine was an independent predictor of postoperative organ injury (odds ratio = 4.81, 95% confidence interval [1.16-19.94]; P = 0.030). CONCLUSIONS: Patients who postoperatively developed organ injury (SOFA score > 3 at 48 h) had preoperatively a longer time to reach the peak of endothelium-dependent vasodilation. Trial registration Clinical-Trials.gov, NCT03631797. Registered 15 August 2018, https://clinicaltrials.gov/ct2/show/NCT03631797.

Cardiopulmonary bypass and internal thoracic artery: Can roller or centrifugal pumps change vascular reactivity of the graft? The IPITA study: A randomized controlled clinical trial.

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response (SIRS) and affects the organ vascular bed. Experimentally, the lack of pulsatility alters myogenic tone of resistance arteries and increases the parietal inflammatory response. The purpose of this study was to compare the vascular reactivity of the internal thoracic arteries (ITAs) due to the inflammatory response between patients undergoing coronary artery bypass grafting (CABG) under CPB with a roller pump or with a centrifugal pump. METHODS: Eighty elective male patients undergoing CABG were selected using one or two internal thoracic arteries under CPB with a roller pump (RP group) or centrifugal pump (CFP group). ITA samples were collected before starting CPB (Time 1) and before the last coronary anastomosis during aortic cross clamping (Time 2). The primary endpoint was the endothelium-dependent relaxation of ITAs investigated using wire-myography. The secondary endpoint was the parietal inflammatory response of arteries defined by the measurements of superoxide levels, leukocytes and lymphocytes rate and gene expression of inflammatory proteins using. Terminal complement complex activation (SC5b-9) and neutrophil activation (elastase) analysis were performed on arterial blood at the same times. RESULTS: Exposure time of ITAs to the pump flow was respectively 43.3 minutes in the RP group and 45.7 minutes in the CFP group. Acetylcholine-dependent relaxation was conserved in the two groups whatever the time. Gene expression of C3 and C4a in the artery wall decreased from Time 1 to Time 2. No oxidative stress was observed in the graft. There was no difference between the groups concerning the leukocytes and lymphocytes rate. SC5b-9 and elastase increased between Time 1 and Time 2. CONCLUSION: Endothelium-dependent relaxation of the internal thoracic arteries was preserved during CPB whatever the type of pump used. The inflammatory response observed in the blood was not found in the graft wall within this time frame. TRIAL REGISTRATION: Name of trial study protocol: IPITA Registration number (ClinicalTrials.gov): NCT04168853.

Do storage solutions protect endothelial function of arterialized vein graft in an experimental rat model?

BACKGROUND: This study aims to compare the effects of storage solutions commonly used in coronary artery bypass grafting on the vascular reactivity in vein graft interposed in arterial position in syngeneic rats. METHODS: Twenty-seven male Lewis rats were sacrified to sample a vein graft implanted 6 weeks ago into abdominal aorta position. The vein grafts were inferior venae cavae initially pretreated with heparinized saline solution (HS) or autologous heparinized blood (AHB) or our referent solution, GALA. The endothelial functionality, the in situ Reactive Oxygen Species (ROS) levels and the histological characteristics were conducted from segments of arterialized vein graft. RESULTS: At 6 weeks, graft thrombosis occurred respectively in 22% of AHB group, 62.5% in the HS group and 82.5% in the GALA group. In each group, significative intimal hyperplasia was observed. After 6 weeks, an endothelium-remodeling layer associated with an increase of wall thickness was observed in each group. Endothelium-dependent tone was reduced in the vein graft regardless of the group. No difference was observed concerning the ROS in vein graft between the different groups. In distal aortic sections, ROS levels were increased in HS and GALA groups. CONCLUSIONS: Storage solutions used in this experimental model of vein graft implanted in arterial position cause graft injury and a complete disappearance of vascular reactivity. GALA solution did not reduce intimal risk hyperplasia when the vein graft was exposed to arterial flow in a rat model.

Genetic Association Analyses Highlight IL6, ALPL, and NAV1 As 3 New Susceptibility Genes Underlying Calcific Aortic Valve Stenosis.

BACKGROUND: Calcific aortic valve stenosis (CAVS) is a frequent and life-threatening cardiovascular disease for which there is currently no medical treatment available. To date, only 2 genes, LPA and PALMD, have been identified as causal for CAVS. We aimed to identify additional susceptibility genes for CAVS. METHODS: A GWAS (genome-wide association study) meta-analysis of 4 cohorts, totaling 5115 cases and 354 072 controls of European descent, was performed. A TWAS (transcriptome-wide association study) was completed to integrate transcriptomic data from 233 human aortic valves. A series of post-GWAS analyses were performed, including fine-mapping, colocalization, phenome-wide association studies, pathway, and tissue enrichment as well as genetic correlation with cardiovascular traits. RESULTS: In the GWAS meta-analysis, 4 loci achieved genome-wide significance, including 2 new loci: IL6 (interleukin 6) on 7p15.3 and ALPL (alkaline phosphatase) on 1p36.12. A TWAS integrating gene expression from 233 human aortic valves identified NAV1 (neuron navigator 1) on 1q32.1 as a new candidate causal gene. The CAVS risk alleles were associated with higher mRNA expression of NAV1 in valve tissues. Fine-mapping identified rs1800795 as the most likely causal variant in the IL6 locus. The signal identified colocalizes with the expression of the IL6 RNA antisense in various tissues. Phenome-wide association analyses in the UK Biobank showed colocalized associations between the risk allele at the IL6 lead variant and higher eosinophil count, pulse pressure, systolic blood pressure, and carotid artery procedures, implicating modulation of the IL6 pathways. The risk allele at the NAV1 lead variant colocalized with higher pulse pressure and higher prevalence of carotid artery stenosis. Association results at the genome-wide scale indicated genetic correlation between CAVS, coronary artery disease, and cardiovascular risk factors. CONCLUSIONS: Our study implicates 3 new genetic loci in CAVS pathogenesis, which constitute novel targets for the development of therapeutic agents.

Early postoperative undernutrition following aortic valve replacement surgery.

BACKGROUND: Experiencing loss of appetite after cardiac surgery is often noted during daily care and has been described by several studies. However, no information is available on either energy needs or spontaneous food intake following aortic valve replacement surgery. The goal of this study was to assess the risk of early postoperative undernutrition following aortic valve replacement in a group of patients who were preoperatively well-nourished. METHODS: Anthropometrics data (body mass index, fat free mass index, albuminemia and prealbuminemia, extracellular water), energy balance and appetite were assessed in a cross-over prospective observational study. . Each subject was enrolled in two procedures: surgery and routine coronary angiograms which were used for control matched assessment. Data were assessed during the pre-procedure period (d-15 to d-1) and the post-procedure period (d0 to d+4). Energy expenditure was determined by indirect calorimetry. RESULTS: 15 patients median aged 73 years old [65-77] were included in the study. In post-surgery period, weight and extracellular water were increased and correlated (r2 = 0.571, p = 0.003). CRP was increased from 2 [2;3] to 91 [73;138] (p = 0.001). Ingested calories decreased from 1451 [1272-1640] kcal to 372 [22-528] kcal (p = 0.001) while energy expenditure was increased from 1358 [1180-1559] kcal to 1613 [1472-1670] kcal (p = 0.002). A severe loss of appetite was noted (p = 0.011). None of these changes were observed in the control phase. CONCLUSION: Energy balance was strongly negative after cardiac surgery. Cardiac surgery increased endogenous metabolism by 20% and a severe loss of appetite decrease food intake by 75%, which does not make it possible to compensate for the increase in resting energy expenditure.

Successfully treated necrotizing fasciitis using extracorporeal life support combined with hemoadsorption device and continuous renal replacement therapy.

INTRODUCTION: Necrotizing fasciitis represents a life-threatening infectious condition that causes spreading necrotisis of superficial fascia and subcutaneous cellular tissues. We describe the case of a patient diagnosed with septic and toxic shocks leading to multiple organ failure successfully treated with a combination of extracorporeal life support, continuous renal replacement therapy, and a hemoadsorption device. METHODS: A 41-year-old patient presented with necrotizing fasciitis and multi-organ failure. Initial extracorporeal life support therapy was implanted, compensating for systolic failure. Due to acute renal failure that persisted in time, continuous renal replacement therapy was added. Despite these treatments and as a last attempt to control the septic condition, a CytoSorb® hemoadsorption device was installed in parallel to the extracorporeal life support circuit and two sessions were run. RESULTS: During the days following CytoSorb® treatment, hemodynamic stabilization was observed, as well as normalization of lactic acidosis and blood parameters. CONCLUSION: This case describes the successful use of CytoSorb® with continuous renal replacement therapy and extracorporeal life support in a combined way to overcome a critical phase of septic shock in a young adult patient. This combination of treatments turned out to be efficient for this patient in the context of necrotizing fasciitis.

Fatal postoperative systemic pulmonary hypertension in benfluorex-induced valvular heart disease surgery: A case report.

RATIONALE: Drug-induced valvular heart disease (DI-VHD) remains an under-recognized entity. PATIENT CONCERNS: This report describes a heart valve replacement which was complicated by intractable systemic pulmonary arterial hypertension in a 61-year-old female with severe restrictive mitral and aortic disease. The diagnosis of valvular disease was preceded by a history of unexplained respiratory distress. The patient had been exposed to benfluorex for 6.5 years. DIAGNOSES: The diagnostic procedure documented specific drug-induced valvular fibrosis. INTERVENTIONS: Surgical mitral and aortic valve replacement was performed. OUTCOMES: Heart valve replacement was postoperatively complicated by unanticipated disproportionate pulmonary hypertension. This issue was fatal despite intensive care including prolonged extracorporeal life support. LESSONS: Benfluorex is a fenfluramine derivative which has been marketed between 1976 and 2009. Although norfenfluramine is the common active and toxic metabolite of all fenfluramine derivatives, the valvular and pulmonary arterial toxicity of benfluorex was much less known than that of fenfluramine and dexfenfluramine. The vast majority of benfluorex-induced valvular heart disease remains misdiagnosed as hypothetical rheumatic fever due to similarities between both etiologies. Better recognition of DI-VHD is likely to improve patient outcome.