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OBJECTIVES Mitral valve replacement using a bioprosthesis remains controversial in young patients because data on long-term outcomes are missing. This study evaluated the long-term results of the PERIMOUNT pericardial mitral bioprosthesis in patients aged 65 years or younger. METHODS From 1984 to 2010, 148 Carpentier–Edwards PERIMOUNT mitral bioprostheses were implanted in 148 patients aged 65 years or younger. Baseline clinical, perioperative and follow-up data were recorded prospectively. Structural valve deterioration (SVD) was defined by strict echocardiographic assessment. RESULTS The mean follow-up period was 8.6 ± 5.5 years, for a total of 1269 valve-years. Operative mortality rate was 2.0%. Fifty-one late deaths occurred (linearized rate 4.0% per valve-year). Actuarial survival rates averaged 70 ± 4%, 53 ± 6% and 31 ± 7% after 10, 15 and 20 years of follow-up, respectively. Actuarial freedom from SVD at 10, 15 and 20 years was 78 ± 5%, 47 ± 7% and 19 ± 7%, respectively. Reoperation was associated with no operative mortality. Actuarial freedom from reoperation due to SVD at 10, 15 and 20 years was 82 ± 4%, 50 ± 6% and 25 ± 8%, respectively. Competing risk analysis demonstrated an actual risk of explantation secondary to SVD at 20 years of 44 ± 5%. Expected valve durability was 14.2 years for this age group. CONCLUSIONS In the selected patients aged 65 years or younger undergoing mitral valve replacement with a pericardial bioprosthesis, the expected valve durability was 14.2 years. Reoperation for SVD was associated with a low risk of mortality. [ABSTRACT FROM AUTHOR]

Bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. A significant challenge when comparing the durability of different types of bioprostheses is the lack of a standardized terminology for the definition of a degenerated valve. This issue becomes especially important when we try to compare the degeneration rate of surgically inserted and transcatheter bioprosthetic valves. This document, by the VIVID (Valve-in-Valve International Data), proposes practical and standardized definitions of valve degeneration and provides recommendations for the timing of clinical and imaging follow-up assessments accordingly. Its goal is to improve the quality of research and clinical care for patients with deteriorated bioprostheses by providing objective and strict criteria that can be utilized in future clinical trials. We hope that the adoption of these criteria by both the cardiological and surgical communities will lead to improved comparability and interpretation of durability analyses. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Aortic valve replacement (AVR) using a bioprosthesis remains controversial for patients aged 50-65 years. This cohort study reports the very long-term outcomes of AVR using Carpentier-Edwards Perimount pericardial bioprosthesis in this age group. METHODS: From 1984 to 2008, 522 Carpentier-Edwards Perimount pericardial aortic bioprostheses were implanted in 516 patients aged 50-65 years (mean age, 60 ± 4 years; 19% female). Multiple valve replacements were excluded fro m our cohort. Baseline demographic, perioperative and follow-up data were recorded prospectively. Mean follow-up was 9 ± 6 years, for a total of 4428 valve-years. Follow-up was complete for 97% of patients included. RESULTS: Operative mortality rate was 2%. One hundred and forty-six late deaths occurred for a linearized rate of 3%/valve-year. Actuarial survival rates averaged 73 ± 2, 59 ± 3 and 35 ± 5% after 10, 15 and 20 years of follow-up, respectively. Mortality rate associated with reoperation was 2%. Actuarial freedom from reoperation rates due to structural valve deterioration (SVD) at 10, 15 and 20 years was respectively of 91 ± 2, 76 ± 3 and 50 ± 6%. Competing risk analysis demonstrated an actual risk of explantation secondary to SVD at 20 years of 30 ± 3%. Expected valve durability was 19 years for this age group. Age was not a significant risk factor for SVD in this middle-aged population. CONCLUSIONS: In patients aged 50-65 years undergoing AVR with the Carpentier-Edwards Perimount bioprosthesis, the expected valve durability was 19 years. Age was not a significant risk factor for SVD within this age group. Patient selection and attention to timing of reintervention may be determinants of long-term outcomes. [ABSTRACT FROM AUTHOR]

Engineering living, multilayered blood vessels to form in vivo arteries is a promising alternative to peripheral artery bypass using acellular grafts restricted by thrombosis and occlusion at long term. Bone Morphogenetic Protein 2 (BMP2) is a growth factor determining in the early vascular embryonic development. The aim of the present study was evaluate the collaborative effect of recombinant human-BMP2 and Bone marrow-Mesenchymal stem cells (BM-MSCs) seeded on vascular patch to regenerate a vascular arterial wall in a rat model. BM-MSCs expressing green fluorescent protein (GFP) seeded on vascular patch were cultured in presence of recombinant human-BMP2 [100 ng/mL] during 1 week before their implantation on the abdominal aorta of Wistar rats. We observed after 2 weeks under physiological arterial flow a regeneration of a three layers adult-like arterial wall with a middle layer expressing smooth muscle proteins and a border layer expressing endothelial marker. In vitro study, using Matrigel assay and co-culture of BM-MSCs with endothelial cells demonstrated that rh-BMP2 promoted tube-like formation even at long term (90 days) allowing the organization of thick rails. We demonstrated using inhibitors and siRNAs that rh-BMP2 enhanced the expression of HIF-1α and Id1 through, at least in part, the stimulation of JAK2/STAT3/STAT5 signaling pathways. Rh-BMP2 by mimicking embryological conditions allowed vascular BM-MSCs differentiation. [ABSTRACT FROM AUTHOR]

Background: There is an ever-growing number of patients requiring aortic valve replacement (AVR). Limited data is available on the long-term outcomes and structural integrity of bioprosthetic valves in younger patients undergoing surgical AVR.Methods: The INSPIRIS RESILIA Durability Registry (INDURE) is a prospective, open-label, multicentre, international registry with a follow-up of 5 years to assess clinical outcomes of patients younger than 60 years who undergo surgical AVR using the INSPIRIS RESILIA aortic valve. INDURE will be conducted across 20-22 sites in Europe and Canada and intends to enrol minimum of 400 patients. Patients will be included if they are scheduled to undergo AVR with or without concomitant root replacement and/or coronary bypass surgery. The primary objectives are to 1) determine VARC-2 defined time-related valve safety at one-year (depicted as freedom from events) and 2) determine freedom from stage 3 structural valve degeneration (SVD) presenting as morphological abnormalities and severe haemodynamic valve degeneration at 5 years. Secondary objectives include the assessment of the haemodynamic performance of the valve, all stages of SVD, potential valve-in-valve procedures, clinical outcomes (in terms of New York Heart Association [NYHA] function class and freedom from valve-related rehospitalisation) and change in patient quality-of-life.Discussion: INDURE is a prospective, multicentre registry in Europe and Canada, which will provide much needed data on the long-term performance of bioprosthetic valves in general and the INSPIRIS RESILIA valve in particular. The data may help to gather a deeper understanding of the longevity of bioprosthetic valves and may expand the use of bioprosthetic valves in patients under the age of 60 years.Trial Registration: ClinicalTrials.gov identifier: NCT03666741 (registration received September, 12th, 2018). [ABSTRACT FROM AUTHOR]

• Acute kidney injury (AKI) occurred in 52.7% of patients with infective endocarditis. • Staphylococcus aureus was the most common species and was associated with AKI. • An infectious disease consultation appeared to be a protective factor for AKI. • Exploration of AKI needs to be systematic to conclude on its aetiologies. • Among the 69% patients who survived at one year, 32% had chronic kidney disease. The incidence of acute kidney injury (AKI) in infective endocarditis (IE), its risk factors and consequences on patient and renal survival remain debated. Patients hospitalized for a first episode of IE (possible or definite according to modified Duke criteria) between 2013 and 2016 were included. The primary endpoint was to determine risk factors for early AKI (E-AKI) during the first week of management of IE. A total of 276 patients were included: 220 (79.7%) had definite IE and 56 (20.3%) had possible IE. E-AKI occurred in 150 patients (53%). IE due to Staphylococcus aureus (OR 3.41; 95% CI 1.83–6.39; p < 0.01), history of diabetes (OR 2.34; 95% CI 1.25–4.37; p < 0.01), peripheral arterial disease (OR 2.59; 95% CI 1.07–6.23; p < 0.05), immunological manifestations (OR 3.11; 95% CI 1.31–7.39; p = 0.01), and use of norepinephrine (OR 3.44; 95% CI 1.72–7.02; p < 0.01) were associated with E-AKI. In subgroup analysis, infectious disease consultation was associated with a lower risk of AKI at day 7 (OR 0.41; 95% CI 0.16–0.88; p = 0.04). E-AKI was associated with 1-year mortality (OR 1.65; 95% CI 1.03–2.64; p = 0.04) and chronic kidney disease progression (OR 2.23; 95% CI 1.30–3.82; p < 0.01). E-AKI is common in IE and often associated with non-modifiable variables. Multidisciplinary management should be mandatory, and awareness of AKI diagnosis and etiological explorations should be raised. [ABSTRACT FROM AUTHOR]

Background: Valve-in-valve (VIV) transcatheter aortic valve replacement (TAVR) and redo surgical aortic valve replacement (SAVR) represent the 2 treatments for aortic bioprosthesis failure. Clinical comparison of both therapies remains limited by the number of patients analyzed.Objectives: The purpose of this study was to analyze the outcomes of VIV TAVR versus redo SAVR at a nationwide level in France.Methods: Based on the French administrative hospital-discharge database, the study collected information for patients treated for aortic bioprosthesis failure with isolated VIV TAVR or redo SAVR between 2010 and 2019. Propensity score matching was used for the analysis of outcomes.Results: A total of 4,327 patients were found in the database. After matching on baseline characteristics, 717 patients were analyzed in each arm. At 30 days, VIV TAVR was associated with lower rates of the composite of all-cause mortality, all-cause stroke, myocardial infarction, and major or life-threatening bleeding (odds ratio: 0.62; 95% confidence interval: 0.44 to 0.88; p = 0.03). During follow-up (median 516 days), the combined endpoint of cardiovascular death, all-cause stroke, myocardial infarction, or rehospitalization for heart failure was not different between the 2 groups (odds ratio: 1.18; 95% confidence interval: 0.99 to 1.41; p = 0.26). Rehospitalization for heart failure and pacemaker implantation were more frequently reported in the VIV TAVR group. A time-dependent interaction between all-cause and cardiovascular mortality following VIV TAVR was reported (p-interaction <0.05).Conclusions: VIV TAVR was observed to be associated with better short-term outcomes than redo SAVR. Major cardiovascular outcomes were not different between the 2 treatments during long-term follow-up. [ABSTRACT FROM AUTHOR]

Background: Two competing transcatheter aortic valve replacement (TAVR) technologies are currently available. Head-to-head comparisons of the relative performances of these 2 devices have been published. However, long-term clinical outcome evaluation remains limited by the number of patients analyzed, in particular, for recent-generation devices.Methods: Based on the French administrative hospital-discharge database, the study collected information for all consecutive patients treated with a TAVR device commercialized in France between 2014 and 2018. Propensity score matching was used for the analysis of outcomes during follow-up. The objective of this study was to analyze the outcomes of TAVR according to Sapien 3 balloon-expandable (BE) versus Evolut R self-expanding TAVR technology at a nationwide level in France.Results: A total of 31 113 patients treated with either Sapien 3 BE or Evolut R self-expanding TAVR were found in the database. After matching on baseline characteristics, 20 918 patients were analyzed (10 459 in each group with BE or self-expanding valves). During follow-up (mean [SD], 358 [384]; median [interquartile range], 232 [10-599] days), BE TAVR was associated with a lower yearly incidence of all-cause death (relative risk, 0.88; corrected P=0.005), cardiovascular death (relative risk, 0.82; corrected P=0.002), and rehospitalization for heart failure (relative risk, 0.84; corrected P<0.0001). BE TAVR was also associated with lower rates of pacemaker implantation after the procedure (relative risk, 0.72; corrected P<0.0001).Conclusions: On the basis of the largest cohort available, we observed that Sapien 3 BE valves were associated with lower rates of all-cause death, cardiovascular death, rehospitalization for heart failure, and pacemaker implantation after a TAVR procedure. [ABSTRACT FROM AUTHOR]

Although many risk models have been tested in patients implanted by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), few scores assessed patients' prognosis in the setting of ST-segment elevation myocardial infarction (STEMI) with refractory cardiogenic shock. We aimed at assessing the performance of risk scores, notably the prEdictioN of Cardiogenic shock OUtcome foR AMI patients salvaGed by VA-ECMO (ENCOURAGE) score, for predicting mortality in this particular population. This retrospective observational study included patients admitted to Tours University Hospital for STEMI with cardiogenic shock and requiring hemodynamic support by VA-ECMO. Among the fifty-one patients, the 30-day and 6-month survival rates were 63% and 56% respectively. Thirty days after VA-ECMO therapy, probabilities of mortality were 12, 17, 33, 66, 80% according to the ENCOURAGE score classes 0–12, 13–18, 19–22, 23–27, and ≥28, respectively. The ENCOURAGE score (AUC of the Receiving Operating Characteristic curve = 0.83) was significantly better compared to other risk scores. The hazard ratio for survival at 30 days for each point of the ENCOURAGE score was 1.10 (CI 95% (1.06, 1.15); p < 0.001). Decision curve analysis indicated that the ENCOURAGE score had the best clinical usefulness of the tested risk scores and the Hosmer–Lemeshow test suggested an accurate calibration. Our data suggest that the ENCOURAGE score is valid and the most relevant score to predict 30-day mortality after VA-ECMO therapy in STEMI patients with refractory cardiogenic shock. It may help decision-making teams to better select STEMI patients with shock for VA-ECMO therapy. [ABSTRACT FROM AUTHOR]

Sterile inflammation is a key determinant of myocardial reperfusion injuries. It participates in infarct size determination in acute myocardial infarction and graft rejection following heart transplantation. We previously showed that P2Y11 exerted an immunosuppressive role in human dendritic cells, modulated cardiofibroblasts' response to ischemia/reperfusion in vitro and delayed graft rejection in an allogeneic heterotopic heart transplantation model. We sought to investigate a possible role of P2Y11 in the cellular response of cardiomyocytes to ischemia/reperfusion. We subjected human AC16 cardiomyocytes to 5 h hypoxia/1 h reoxygenation (H/R). P2Y11R (P2Y11 receptor) selective agonist NF546 and/or antagonist NF340 were added at the onset of reoxygenation. Cellular damages were assessed by LDH release, MTT assay and intracellular ATP level; intracellular signaling pathways were explored. The role of P2Y11R in mitochondria-derived ROS production and mitochondrial respiration was investigated. In vitro H/R injuries were significantly reduced by P2Y11R stimulation at reoxygenation. This protection was suppressed with P2Y11R antagonism. P2Y11R stimulation following H2O2-induced oxidative stress reduced mitochondria-derived ROS production and damages through PKCε signaling pathway activation. Our results suggest a novel protective role of P2Y11 in cardiomyocytes against reperfusion injuries. Pharmacological post-conditioning targeting P2Y11R could therefore contribute to improve myocardial ischemia/reperfusion outcomes in acute myocardial infarction and cardiac transplantation. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of acute rejection in cardiac transplant recipients requires invasive technique with endomyocardial biopsy (EMB) which has risks and limitations. Cardiovascular magnetic resonance imaging (CMR) with T2 and T1 mapping is a promising technique for characterizing myocardial tissue. The purpose of the study was to evaluate T2, T1 and extracellular volume fraction (ECV) quantification as novel tissue markers to diagnose acute rejection. Methods: CMR was prospectively performed in 20 heart transplant patients providing 31 comparisons EMB-CMR. CMR was performed close to EMB. Images were acquired on a 1.5 Tesla scanner including T2 mapping (T2 prepared balanced steady state free precession) and T1 mapping (modified Look-Locker inversion recovery sequences: MOLLI) at basal, mid and apical level in short axis view. Global and segmental T2 and T1 values were measured before and 15 min (for T1 mapping) after contrast administration. Results: Acute rejection was diagnosed in seven patients: six cellular rejections (4 grade IR, 2 grade 2R) and one antibody mediated rejection. Patients with acute rejection had significantly higher global T2 values at 3 levels: 58.5 ms [55.0–60.3] vs 51.3 ms [49.5–55.2] (p = 0.007) at basal; 55.7 ms [54.0–59.7] vs 51.8 ms [50.1–53.6] (p = 0.002) at median and 58.2 ms [54.0–63.7] vs 53.6 ms [50.8–57.4] (p = 0.026) at apical level. The area under the curve (AUC) for each level was 0.83, 0.79 and 0.78 respectively. Patients with acute rejection had significantly higher ECV at basal level: 34.2% [32.8–37.4] vs 27.4% [24.6–30.6] (p = 0.006). The AUC for basal level was 0.84. The sensitivity, specificity and diagnosis accuracy for basal T2 (cut off: 57.7 ms) were 71, 96 and 90% respectively; and for basal ECV: (cut off 32%) were 86, 85 and 85% respectively. Combining basal T2 and basal ECV allowed diagnosing all acute rejection and avoiding 63% of EMB. Conclusions: In heart transplant patients, a combined CMR approach using T2 mapping and ECV quantification provides a high diagnostic accuracy for acute rejection diagnosis and could potentially decrease the number of routine EMB. [ABSTRACT FROM AUTHOR]