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We study the measurable dynamical properties of the interval map generated by the model-case erasing substitution $\rho $ , defined by $$ \begin{align*} \rho(00)=\text{empty word},\quad \rho(01)=1,\quad \rho(10)=0,\quad \rho(11)=01. \end{align*} $$ We prove that, although the map is singular, its square preserves the Lebesgue measure and is strongly mixing, thus ergodic, with respect to it. We discuss the extension of the results to more general erasing maps.

The inherited connective tissue disorders (Marfan syndrome, Loeys-Dietz syndrome [LDS], and Ehlers-Danlos syndrome [EDS]) involve connective tissue of various organ systems. These pathologies share many common features, nonetheless compared to Marfan syndrome, LDS' cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis. The EDS are currently classified into thirteen subtypes. There is substantial symptoms overlap between the EDS subtypes, and they are associated with an increased incidence of cardiovascular abnormalities, such as mitral valve prolapse and aortic dissection.

Objectives: The role of the underlying etiology in isolated tricuspid valve surgery has not been investigated extensively in current literature. Aim of this study was to analyse outcomes of patients undergoing surgery due to endocarditis compared to other pathologies. Methods: The SURTRI study is a multicenter study enrolling adult patients who underwent isolated tricuspid valve surgery (n=406, 55±16 y.o.; 56% female) at 13 international sites. Propensity weighted analysis was performed to compare groups (IE group n=107 vs Not-IE group n=299). Results: No difference was found regarding the 30-day mortality (Group IE: 2.8% vs Group Not-IE=6.8%; OR=0.45) and major adverse events. Weighted cumulative incidence of cardiac death was significantly higher for patients with endocarditis (p=0.01). The composite endpoint of cardiac death and reoperation at 6years was reduced in the Group IE (63.2±6.8% vs 78.9±3.1%; p=0.022). Repair strategy resulted in an increased late survival even in IE cases. Conclusions: Data from SURTRI study report acceptable 30-day results but significantly reduced late survival in the setting of endocarditis of the tricuspid valve. Multi-disciplinary approach, repair strategy and earlier treatment may improve outcomes.

OBJECTIVES The prevalence and aetiology of acute aortic dissection type A (AADA) in patients ≤30 years is unknown. The aims of this clinical study were to determine the prevalence and potential aetiology of AADA in surgically treated patients ≤30 years and to evaluate the respective postoperative outcomes in this selective group of patients in a large multicentre study. METHODS Retrospective data collection was performed at 16 participating international aortic institutions. All patients ≤30 years at the time of dissection onset were included. The postoperative results were analysed with regard to connective tissue disease (CTD). RESULTS The overall prevalence of AADA ≤30 years was 1.8% (139 out of 7914 patients), including 51 (36.7%) patients who were retrospectively diagnosed with CTD. Cumulative postoperative mortality was 8.6%, 2.2% and 1.4%. Actuarial survival was 80% at 10 years postoperatively. Non-CTD patients (n = 88) had a significantly higher incidence of arterial hypertension (46.6% vs 9.8%; P CONCLUSIONS The prevalence of AADA in surgically treated patients ≤30 years is

It is currently believed that plaque complication, with the consequent superimposed thrombosis, is a key factor in the clinical occurrence of acute coronary syndromes (ACSs). Platelets are major players in this process. Despite the considerable progress made by the new antithrombotic strategies (P2Y12 receptor inhibitors, new oral anticoagulants, thrombin direct inhibitors, etc.) in terms of a reduction in major cardiovascular events, a significant number of patients with previous ACSs treated with these drugs continue to experience events, indicating that the mechanisms of platelet remain largely unknown. In the last decade, our knowledge of platelet pathophysiology has improved. It has been reported that, in response to physiological and pathological stimuli, platelet activation is accompanied by de novo protein synthesis, through a rapid and particularly well-regulated translation of resident mRNAs of megakaryocytic derivation. Although the platelets are anucleate, they indeed contain an important fraction of mRNAs that can be quickly used for protein synthesis following their activation. A better understanding of the pathophysiology of platelet activation and the interaction with the main cellular components of the vascular wall will open up new perspectives in the treatment of the majority of thrombotic disorders, such as ACSs, stroke, and peripheral artery diseases before and after the acute event. In the present review, we will discuss the novel role of noncoding RNAs in modulating platelet function, highlighting the possible implications in activation and aggregation.

Background Despite optimal therapy, heart failure (HF) remains a relentless and deadly disease. Given the relative inaccessibility of myocardial human tissues, identification of circulating biomarkers mirroring myocardial pathological signaling pathways, especially in peripheral blood mononuclear cells (PBMC) is expected to be extremely relevant. Small Nucleolar RNAs (snoRNAs) have been shown to play important roles in various cellular physiological processes. However, the connection between snoRNAs and pathological dysfunction in the heart or peripheral blood mononuclear cells (PBMC) is still poorly understood. Purpose To identify novel circulating PBMC biomarkers linked to myocardial dysfunction and HF. Methods : Myocardial left ventricle (LV) samples and PBMC were obtained from patients affected by ischemic HF (HF, n =13) undergoing heart transplantation and control donors (CD, n=7) and analyzed by RNA sequencing analysis (RNASeq). SNORD3A expression levels in the different groups were evaluated by quantitative real-time PCR. HF was induced in 8-week-old wild type C57BL/6 mice by transverse aortic constriction (TAC). Sham-operated mice (sham) were used as controls. After twelve-week-TAC (12w) or sham operation, mice were anesthetized, cardiac function was analyzed by echocardiography, and cardiac/PBMC samples were collected after sacrifice. In order to test the role of SNORD3A in cardiomyocyte hypoxia, H9C2 cardiomyoblasts were transfected with SNORD3A-targeted antisense oligonucleotides (ASO) and cell survival was analyzed. Results RnaSeq analysis identified a small set of genes differentially expressed in the heart and PBMC from HF patients. Among these, SNORD3A was up-regulated in cardiac and PBMC samples from HF patients compared to CD (Figure 1A). Similarly, in murine HF induced by 12w TAC, SNORD3A levels were increased by rtPCR, both in the heart and PBMC (Figure 1B). SNORD3A expression levels were also significantly increased in H9C2 cells exposed to in vitro hypoxia (Figure 1C). Interestingly, H9C2 transfection with SNORD3A-specific ASO significantly reduced hypoxia-induced SNORD3A upregulation and reduced hypoxia-induced cell death (Figure 1D). Conclusions In this study, we identify SNORD3A as a novel possible biomarker in human HF, similarly up-regulated in the heart and PBMC, induced by hypoxia in vitro and modulating cell survival.

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

OBJECTIVESThis retrospective observational study aimed to assess the geometrical features, including diameters, length and angulation, of the ascending aorta with bicuspid and tricuspid aortic valve and to identify imaging markers potentially predicting whether aortopathy is likely to evolve chronically or to complicate with acute type A dissection.METHODSAngio-computed-tomography scans of 354 patients (from 3 centres) with non-dilated (n = 97), aneurysmal (n = 100) or dissected aorta (n = 157) were reviewed. Diameters were measured at root, sinotubular junction, ascending, brachio-cephalic trunk origin; centreline lengths of the root and tubular tract and ascending-arch angle (between the ascending tubular tract axis and the proximal arch axis) were also measured. For 12 dissection patients, pre-dissection scans were available to investigate predisposing aortic geometry. Statistical analysis included: tricuspid versus bicuspid comparisons in each subgroup; univariate and multivariate analyses of the predictors of ascending-arch angle narrowing; and estimation of diagnostic accuracy of the angle parameter.RESULTSDiameters and lengths were similar between aneurysms and dissections, whereas dissections showed a significant ascending-arch angle narrowing (117 ± 13° in tricuspid, 115 ± 14° in bicuspid) compared to non-dilated and aneurysmal aortas (all P CONCLUSIONSThe ascending-arch angle is promising as a risk marker for dissection to be used along with diameter. Its narrowing seems to be associated with elongation of the root, a feature that bicuspid patients can show even without significant dilatation. Root phenotype aortopathy may be at higher risk also with tricuspid aortic valve.

BACKGROUND: Aim of this study is to analyse the performances of Clinical Risk Score (CRS) and European System for Cardiac Operative Risk Evaluation (EuroSCORE)-II in isolated tricuspid surgery.METHODS: Three hundred and eighty-three patients (54 ± 16 year; 54% female) were enrolled. Receiver operating characteristic analysis was performed to evaluate the relationship between the true positive fraction of test results and the false-positive fraction for a procedure.RESULTS: Considering the 30-day mortality the area under the curve was 0.6 (95% confidence interval [CI] 0.50-0.72) for EuroSCORE II and 0.7 (95% CI 0.56-0.84) for CRS-score. The ratio of expected/observed mortality showed underestimation when considering EuroSCORE-II (min. 0.46-max. 0.6). At multivariate analysis, the CRS score (p = .005) was predictor of late cardiac death.CONCLUSION: We suggest using both scores to obtain a range of expected mortality. CRS to speculate on late survival.

Background Scarce data are available on the long-term outcomes of different regimens of oral anticoagulation in an all comer population of patients undergoing aortic valve replacement with a bileaflet mechanical heart valve. Methods Outcomes of 88 patients discharged with a target INR of 2.0 (LOW-INR) were compared to 147 contemporary patients who have been recommended a target INR of 2.5 (CONV). Primary outcome was the composite of any thromboembolic or haemorrhagic events. Secondary outcomes were the individual components of the primary outcome, cardiovascular mortality and stroke. To reduce selection bias, a propensity weighted analysis was performed. Results After inverse probability of treatment weighting, the primary endpoint occurred in 0.7% of patient in the LOW-INR group and in 7.0% in the CONV group (p = .0255). Linearized event rate were significantly lower in the LOW-INR group (primary endpoint: rate difference − 12.0 per 1000 patient/years, p = .0052; haemorrhage: −5.8 per 1000 patient/years, p = .0330; neurological events: −7.6 per 1000 patient/years, p = .0140). Conventional target INR was associated with an increased hazard of the composite endpoint (HR 11.193, 95% CI 1.424–88.003, p = .0217). Conclusions Lowering the intensity of oral anticoagulation resulted in a relevant clinical benefit of reduced rates of haemorrhagic and neurological adverse events in the mid-term follow-up. This report confirms the safety profile of the low INR regimen in an all comer population undergoing aortic valve replacement with an Abbott mechanical valve.

AIMS: To compare early and late mortality of acute isolated tricuspid valve infective endocarditis (TVIE) treated with valve repair or replacement.METHODS: Patients who were surgically treated for TVIE from 1983 to 2018 were retrieved from the Italian Registry for Surgical Treatment of Valve and Prosthesis Infective Endocarditis. All the patients were followed up by means of phone interview or calling patient referral physicians or cardiologists. Kaplan-Meier method was used to assess late survival and survival free from TVIE recurrence with log-rank test for univariate comparison. The primary end points were early mortality (30 days after surgery) and long-term survival free from TVIE recurrence.RESULTS: A total of 4084 patients were included in the registry. Among them, 149 patients were included in the study. Overall, 77 (51.7%) underwent TV repair and 72 (48.3%) TV replacement. Early mortality was 9% (13 patients). Expected early mortality according to EndoSCORE was 12%. The TV repair showed lower mortality and major complication rate (7% and 16%), compared with TV replacement (11% and 25%), but statistical significance was not reached. Median follow-up was 19.1 years (14.3-23.8). Late deaths were 30 and IE recurrences were 5. No difference in cardiac survival free from IE was found between the two groups after 20 years (80 ± 6% Repair Group vs 59 ± 13% Replacement Group, P = 0.3).CONCLUSIONS: Overall results indicate that once surgically addressed, TVIE has a low recurrence rate and excellent survival, apparently regardless of the type of surgery used to treat it.

no abstract available

BACKGROUND Isolated tricuspid valve (TV) surgery is a rare procedure generally considered at high risk for perioperative mortality and poor long-term outcomes. Surgical treatment can be performed with either an arrested heart (AH) or beating heart (BH) technique. The aim of this study was to compare the outcomes of isolated tricuspid surgery with 2 different approaches.METHODS The Surgical-Tricuspid Study is a multicenter international retrospective study enrolling adult patients who un- derwent isolated TV procedures (n = 406; age 56 +/- 16 years; 56% female) at 13 international sites. The AH and BH strategies were performed in 253 and 153 patients, respectively. Propensity score-matched analysis was used to compare groups.RESULTS After matching, 129 pairs were obtained and analyzed. The 30-day mortality rate was 6.2% versus 5.0% in the AH and BH groups, respectively (P = .9). The rates of acute renal failure requiring replacement therapy (10% versus 3%; P = .02) and stroke (1.6% versus 0%; P = .08) were numerically higher in the AH group. The 6-year survival rate was 67% +/- 6% versus 78% +/- 5% in the AH and BH groups, respectively (P = .18), whereas freedom from cardiac death was 75% +/- 5% versus 84% +/- 4% (P = .21). The 6-year composite cardiac end point of cardiac death and reoperation rate was 60% +/- 9% versus 86% +/- 5% (P - .024) comparing AH-TV replacement and BH-TV repair groups.CONCLUSIONS Isolated TV surgery performed with a BH strategy is a safe option and resulted in a trend of increased long-term survival and freedom from reoperation compared with the standard AH technique. Patients undergoing BH valve repair had the best long-term outcome. (C) 2022 by The Society of Thoracic Surgeons

Aims Despite optimal therapy, heart failure (HF) remains a relentless and deadly disease. Given the relative inaccessibility of myocardial human tissues, identification of circulating biomarkers mirroring myocardial pathological signalling pathways, especially in peripheral blood mononuclear cells (PBMC) is expected to be extremely relevant. Small Nucleolar RNAs (snoRNAs) have been shown to play important roles in various cellular physiological processes. However, the connection between snoRNAs and pathological dysfunction in the heart or peripheral blood mononuclear cells (PBMC) is still poorly understood. To identify novel circulating PBMC biomarkers linked to myocardial dysfunction and HF. Methods Myocardial left ventricle (LV) samples and PBMC were obtained from patients affected by ischaemic HF (HF, n = 13) undergoing heart transplantation and control donors (CD, n = 7) and analysed by RNA sequencing analysis (RNASeq). SNORD3A expression levels in the different groups were evaluated by quantitative real-time PCR. HF was induced in 8-week-old wild type C57BL/6 mice by transverse aortic constriction (TAC). Sham-operated mice (sham) were used as controls. After 12-week-TAC (12w) or sham operation, mice were anesthetized, cardiac function was analysed by echocardiography, and cardiac/PBMC samples were collected after sacrifice. In order to test the role of SNORD3A in cardiomyocyte hypoxia, H9C2 cardiomyoblasts were transfected with SNORD3A-targeted antisense oligonucleotides (ASO) and cell survival was analysed. Results RNASeq analysis identified a small set of genes differentially expressed in the heart and PBMC from HF patients. Among these, SNORD3A was up-regulated in cardiac and PBMC samples from HF patients compared to CD (Figure 1A). Similarly, in murine HF induced by 12w TAC, SNORD3A levels were increased by rtPCR, both in the heart and PBMC (Figure 1B). SNORD3A expression levels were also significantly increased in H9C2 cells exposed to in vitro hypoxia (Figure 1C). Interestingly, H9C2 transfection with SNORD3A-specific ASO significantly reduced hypoxia-induced SNORD3A up-regulation and reduced hypoxia-induced cell death (Figure 1D). Conclusions In this study, we identify SNORD3A as a novel possible biomarker in human HF, similarly up-regulated in the heart and PBMC, induced by hypoxia in vitro and modulating cell survival.

Background: To assess early and late mortality in patients with isolated acute tricuspid valve infective endocarditis (TVIE) using data from a multicenter registry.Methods: From 1983 to 2018, isolated acute TVIE was surgically treated in 157 (3.8%) patients [mean age 47 +/- 16 years (range 15-86 years), 25% females]. Of these, 142 (90%) had native tricuspid regurgitation, 7 (5%) native tricuspid valve (TV) steno-regurgitation, and 8 (5%) prosthetic TVIE. Intravenous drug use (IVDU) was recorded in 38% of patients, infection involved cardiac implantable electronic device leads in 21%, and vascular catheters for dialysis in 1%; in the remaining cases, the cause was unknown. The primary endpoint was in-hospital outcome, long-term freedom from recurrence and overall survival.Results: Overall, 77 (49%) patients underwent TV repair, 72 (46%) TV replacement, and 8 (5%) prosthetic TV replacement. Early mortality was 11% (n = 17). Expected early mortality according to EndoSCORE was 12%, with age (odds ratio 1.06) and redo (odds ratio 6.64) as risk factors. Late deaths occurred in 31 patients and TVIE recurrences in 4. Survival rates at 10, 20, and 25 years were 66%, 60%, and 44%, respectively. Risk factors were age [hazard ratio (HR) 1.06], mycotic TVIE (HR 4.2), IVDU (HR 4.90), infected prosthesis replacement (HR 4.4), and presence of cardiac implantable electronic device leads (HR 3.0). No significant difference was found in valve repair vs. replacement and in IVDUs vs. non-IVDUs.Conclusions: Patients with isolated acute TVIE undergoing surgical treatment show acceptable early and late outcomes. TVIE recurrence was low, and repair of the affected valve does not seem to confer any advantage either at early or long term up to 25 years. (C) 2019 Elsevier B.V. All rights reserved.

Background: Coronavirus disease 2019 (COVID-19) has been implicated in a wide spectrum of cardiac manifestations following the acute phase of the disease. Objectives: To assess the range of cardiac sequelae after COVID-19 recovery. Data sources: PubMed, Embase, Scopus (inception through 17 February 2021) and Google scholar (2019 through 17 February 2021). Study eligibility criteria: Prospective and retrospective studies, case reports and case series. Participants: Adult patients assessed for cardiac manifestations after COVID-19 recovery. Exposure: Severe acute respiratory syndrome coronavirus 2 infection diagnosed by PCR. Methods: Systematic review. Results: Thirty-five studies (fifteen prospective cohort, seven case reports, five cross-sectional, four case series, three retrospective cohort and one ambidirectional cohort) evaluating cardiac sequelae in 52 609 patients were included. Twenty-nine studies used objective cardiac assessments, mostly cardiac magnetic resonance imaging (CMR) in 16 studies, echocardiography in 15, electrocardiography (ECG) in 16 and cardiac biomarkers in 18. Most studies had a fair risk of bias. The median time from diagnosis/recovery to cardiac assessment was 48 days (1–180 days). Common short-term cardiac abnormalities (

Patients with bicuspid aortic valve (BAV) have an increased risk of aortic dilation and aortic dissection or rupture. The impact of physical training on the natural course of aortopathy in BAV patients remains unclear. The aim of this study was to evaluate the impact of regular physical activity on aortic diameters in a consecutive cohort of paediatric patients with BAV. Consecutive paediatric BAV patients were evaluated and categorized into two groups: physically active and sedentary subjects. Only the subjects with a complete 2-year follow-up were included in the study. To evaluate the potential impact of physical activity on aortic size, aortic diameters were measured at the sinus of Valsalva and mid-ascending aorta using echocardiography. We defined aortic diameter progression the increase of aortic diameter ≥ 10% from baseline. Among 90 BAV patients (11.5 ± 3.4 years of age, 77% males), 53 (59%) were physically active subjects. Compared to sedentary, physically active subjects were not significantly more likely to have > 10% increase in sinus of Valsalva (13% vs. 8%, p-value = 0.45) or mid-ascending aorta diameter (9% vs. 13%, p-value = 0.55) at 2 years follow-up, both in subjects with sinus of Valsalva diameter progression (3.7 ± 1.0 mm vs. 3.5 ± 0.8 mm, p-value = 0.67) and in those with ascending aorta diameter progression (3.0 ± 0.8 mm vs. 3.2 ± 1.3 mm, p-value = 0.83). In our paediatric cohort of BAV patients, the prevalence and the degree of aortic diameter progression was not significantly different between physically active and sedentary subjects, suggesting that aortic dilation is unrelated to regular physical activity over a 2-year period.

OBJECTIVES The aim of this study was to evaluate the effects of the coronavirus 2019 pandemic on elective and acute thoracic aortic surgery in the Netherlands. METHODS The Netherlands Heart Registration database was used to compare the volume of elective and acute surgery on the thoracic aorta in 2019 and 2020, starting from week 11 in both years. A sub-analysis was done to assess the impact of the pandemic on high-volume and low-volume aortic centres. RESULTS During the pandemic, the number of elective thoracic aortic operations declined by 18% [incidence rate ratio (IRR) 0.82 [0.73–0.91]; P < 0.01]. The decline in volume of elective surgery was significant in both high-volume (IRR 0.82 [0.71–0.94]; P < 0.01) and low-volume aortic centres (IRR 0.81 [0.68–0.98]; P = 0.03). The overall number of acute aortic operations during the pandemic remained similar to that in 2019 (505 vs 499; P = 0.85), but an increased share of these operations occurred at high-volume centres. The number of acute operations performed in high-volume centres increased by 20% (IRR 1.20 [1.01–1.42]; P = 0.04), while the number of acute operations performed in low-volume centres decreased by 17% (IRR 0.83 [0.69–1.00]; P = 0.04). CONCLUSIONS The coronavirus 2019 pandemic led to a significant decrease in elective thoracic aortic surgery but did not cause a change in the volume of acute thoracic aortic surgery in the Netherlands. Moreover, the pandemic led to a centralization of care for acute thoracic aortic surgery., The coronavirus disease 19 (COVID-19) pandemic has impacted the delivery of health care around the world.

The current management of aortic dilatation associated with congenital bicuspid aortic valve (bicuspid aortic valve aortopathy) is based on dimensional parameters (diameter of the aneurysm, growth of the diameter over time) and few other criteria. The disease is however heterogeneous in terms of natural and clinical history and risk of acute complications, ie aortic dissection. Dimensional criteria are now admitted to have limited value as predictors of such complications. Thus, novel principles for risk stratification have been recently investigated, including phenotypic criteria, flow-related metrics, and circulating biomarkers. A systematization of the typical anatomoclinical forms that the aortopathy can assume has led to the identification of the more severe root phenotype, associated with higher risk of progression of the aneurysm and possible higher aortic dissection risk. Four-dimensional-flow magnetic resonance imaging studies are searching for potentially clinically significant metrics of flow derangement, based on the recognized association of local abnormal shear stress with wall pathology. Other research initiatives are addressing the question whether circulating molecules could predict the presence or, more importantly, the future development of aortopathy. The present review summarizes the latest progresses in the knowledge on risk stratification of bicuspid aortic valve aortopathy, focusing on critical aspects and debated points.

Objectives: Our goal was to investigate whether the incidence of valve-related adverse events might be different depending on the valve substitute after valve replacement for left-sided native valve endocarditis. Methods: We assessed the long-term freedom from recurrence, reoperation and survival of 395 patients who had valve replacements for native valve endocarditis (314 mechanical vs 81 biological). Age

There is a growing need to develop a common language when referring to a frequent and heterogeneous condition such as the congenital bicuspid aortic valve and its aortopathy. The following short manuscript serves as an introduction to a standard terminology for the bicuspid aortic valve and its aortopathy.(c) 2020 Elsevier Inc. All rights reserved.

The aortopathy associated with bicuspid aortic valve (BAV) is an epidemiologically relevant source of chronic and acute aortic disease (aneurysm and dissection). However, its pathogenesis is still the object of scientific uncertainties and debates. Indeed, the mechanisms determining the diseases of the ascending aorta in BAV patients are most likely complex and multifactorial, i.e. resulting from variable modes of interplay between genetic and hemodynamic factors. Although few scientific studies have so far taken into adequate account this complexity, leaving the precise sequence of pathogenetic events still undiscovered, the accumulated evidence from previous research approaches have at least brought about important insights. While genetic studies have so far identified variants relevant to either valve malformation or aortic complications (including those in the genes NOTCH1, TGFBR2, ACTA2, GATA5, NKX2.5, SMAD6, ROBO4), however each explaining not more than 5% of the study population, other investigations have thoroughly described both the flow features, with consequent forces acting on the arterial wall (including skewed flow jet direction, rotational flow, wall shear stress), and the main changes in the molecular and cellular wall structure (including extracellular matrix degradation, smooth muscle cell changes, oxidative stress, unbalance of TGF-beta signaling, aberrant endothelia l-tomesenchymal transition). All of this evidence, together with the recognition of the diverse phenotypes that the aortopathy can assume in BAV patients, holding possible prognostic significance, is reviewed in this chapter. The complex and multifaceted body of knowledge resulting from clinical and basic science studies on BAV aortopathy has the potential to importantly influence modes of clinical management of this disease in the near future. Crown Copyright (c) 2020 Published by Elsevier Inc. All rights reserved.

OBJECTIVES We aimed to compare the intracellular proteome of ascending aortas from patients with stenotic bicuspid (BAV) and tricuspid aortic valves (TAV) to identify BAV-specific pathogenetic mechanisms of aortopathy and to verify the previously reported asymmetric expression of BAV aortopathy [concentrated at the convexity (CVX)] in its ‘ascending phenotype’ form. METHODS Samples were collected from the CVX and concavity sides of non-aneurysmal ascending aortas in 26 TAV and 26 BAV patients undergoing stenotic aortic valve replacement. Aortic lysates were subjected to cellular protein enrichment by subfractionation, and to proteome comparison by 2-dimensional fluorescence difference in-gel electrophoresis. Differentially regulated protein spots were identified by liquid chromatography–tandem mass spectrometry and analysed in silico. Selected results were verified by immunofluorescence and reverse transcription-polymerase chain reaction. RESULTS In BAV samples, 52 protein spots were differentially regulated versus TAV samples at the CVX and 10 spots at the concavity: liquid chromatography–tandem mass spectrometry identified 35 and 10 differentially regulated proteins, respectively. Charge trains of individual proteins (e.g. annexins) suggested the presence of post-translational modifications possibly modulating their activity. At the CVX, 37 of the 52 different protein spots showed decreased expression in BAV versus TAV. The affected biological pathways included those involved in smooth muscle cell contractile phenotype, metabolism and cell stress. CONCLUSIONS The observed differential proteomics profiles may have a significant impact on the pathogenesis of the aortopathy, pointing the way for further studies. At a preaneurysmal stage, an aorta with BAV shows more protein expression changes and potentially more post-translational modifications at the CVX of the ascending aorta than at the concavity, compared to that of TAV.

The bicuspid aortic valve (BAV) condition is characterized by prominent heterogeneity of its valvular phenotypic expression, of its associated disorders, its complications and its prognosis. Echocardiography serves as the first-line imaging modality in 5 major capacities: (1) BAV diagnosis, (2) valvular phenotyping, (3) assessment of valvular function, (4) measurement of the thoracic aorta and exclusion of aortic coarctation, and (5) assessment of uncommon but serious complications such as infective endocarditis and aortic dissection. This article presents a nosological perspective on the BAV condition, discusses the critical role of echocardiography as it relates to these 5 aforementioned capacities; and makes the case for a unified standard nomenclature for the BAV condition.

Introduction: Thromboembolic complications are due to a complex interplay between patients’ characteristics, device features and anticoagulation intensity. Subtle design and material differences in available prostheses imply different susceptibility to thrombosis. This post hoc sub analysis of the LOWERING-IT database tested the safety and feasibility of a low-level oral anticoagulant regime in low-risk patients with aortic LivaNova prosthetic valve replacement. Methods: Study population included 148 patients randomized to LOW-INR group, and 144 patients randomized to CONVENTIONAL-INR group. The non inferiority of thromboembolic events between LOW-INR and CONVENTIONAL-INR groups was tested. Results: The two groups were well matched. Cumulative follow-up reached 1,545 patient/years. The mean INR was 1.91 ± 0.23 in the LOW-INR group, and 2.59 ± 0.26 in the CONVENTIONAL-INR group (P

OBJECTIVES: We tested the possible value of routine aggregometry testing for bleeding prediction following coronary artery bypass grafting in patients who received preoperative double antiplatelet therapy.METHODS: In 226 patients undergoing on-pump isolated coronary artery bypass grafting, aggregometry [adenosine diphosphate (ADP) test and ASPI test] was always prospectively performed by Multiplate (R) analyser immediately before surgery. We assessed the differences in postoperative bleeding according to the type of double antiplatelet therapy [acetylsalicylic acid plus clopidogrel (ASA+C), or plus ticagrelor (ASA+T)], duration of clopidogrel/ticagrelor withdrawal (0-3 days or >= 4 days) and results of aggregometry tests. Multivariable predictors of blood losses were sought by linear regressions (drainage amount at 6, 12 and 24 postoperative hours) and logistic regression (increased bleeding: 75th percentile of blood losses at 6 h, i.e. > 450 ml).RESULTS: Overall, postoperative blood losses did not significantly differ between treatment groups (median at 6 h: ASA + C = 335 ml, ASA + T = 300 ml, P = 0.21). With longer withdrawal interval, higher rates of patients with normal ADP-related platelet function were observed in both groups (ASA + C: P = 0.04; ASA + T: P = 0.006) but only in the ASA + T group were blood losses significantly smaller at all 3 time points. Bleeders (> 450 ml at 6 h) were significantly less frequent among patients with ADP test showing recovered platelet function (ASA + T: P = 0.002; ASA + C: P = 0.053). The correlation between ADP test result and blood losses amount was stronger in the ASA + T group (e.g. at 6 h: r = -0.6; P < 0.001). In multivariable analyses, the ADP test result independently predicted postoperative bleeding in the ASA + T group and the ASPI test in the ASA + C group.CONCLUSIONS: Aggregometry can help in predicting postoperative bleeding in double antiplatelet therapy patients undergoing coronary artery bypass grafting.

International audience; Continuum mechanics always supplies approximate models for physical systems, in which a more fundamental (possibly discrete or inhomogeneous) microstructure may be somehow neglected. Indeed, Cauchy (or Cauchy-Navier) continuum theory describes efficiently, at a macroscopic level, the behavior of a mechanical system only when the inhomogeneities which the model does not take into account have a characteristic length scale much smaller than the macroscale where phenomena are observed.Therefore, it is now widely accepted that in some circumstances, it is necessary to add to the placement field some extra kinematical fields, to take into account, at a macroscopic level, some aspects of the mechanical behavior of materials having complex microscopic...

In this paper we study a recently proposed mathematical model for the description of the mechanics of bone as well as bone remodeling processes and bone cell populations dynamics. We investigate the biological meaning and a suitable value for the numerical parameters of the model. To do so, we compare biological data with a systematic numerical investigation of the model. We also propose some corrections to the original model aimed at better describing the observed phenomena.