Publications by authors named "Alexis Théron"

42 Publications

Rapid deployment versus trans-catheter aortic valve replacement in intermediate-risk patients: A propensity score analysis.

J Card Surg 2021 Jun 9;36(6):2004-2012. Epub 2021 Mar 9.

Department of Cardiac Surgery, La Timone Hospital, Marseille, France.

Background: There are insufficient studies comparing rapid deployment aortic valve replacement (RDAVR) and trans-aortic valve replacement (TAVR) in intermediate-risk patients with severe aortic stenosis (AS).

Aims: We compared 2-year outcomes between RDAVR with INTUITY and TAVR with SAPIEN 3 in intermediate-risk patients with AS.

Methods: Inclusion criteria were patients with severe AS at a EuroSCORE II ≥ 4%, who received RDAVR or TAVR implantation and clinical evaluation by the Heart Team. Regression adjustment for the propensity score was used to compare RDAVR and TAVR. Primary outcome was the composite criterion of death, disabling stroke, or rehospitalization.

Secondary Outcomes: major bleeding complications postoperation, paravalvular regurgitation ≥ 2, patient-prosthesis mismatch, and pacemaker implantation.

Results: A total of 152 patients were included from 2012 to 2018: 48 in the RDAVR group and 104 in the TAVR group. The mean age was 82.7 ± 6.0,51.3% patients were female, the mean EuroSCORE II was 6.03 ± 1.6%, mean baseline LVEF was 56 ± 13%, mean indexed effective orifice area was 0.41 ± 0.1 cm/m , and the mean gradient was 51.7 ± 14.7 mmHg. RDAVR patients were younger (79.5 ± 6 years vs. 82.6 ± 6 years; p = .01), and at higher risk (EuroSCORE II, 6.61 ± 1.8% vs. 5.63 ± 1.5%; p = .005), Twenty-two patients (45.99%) in the RDAVR group and 32 (66.67%) in the TAVR group met the composite criterion. Through the 1:1 propensity score matching analysis, there was a significant difference between the groups, favoring RDAVR (HR = 0.58 [95% CI: 0.34-1.00]; p = .04). No differences were observed in terms of patient-prosthesis mismatch (0.83 [0.35-1.94]; p = .67), major bleeding events (1.33 [0.47-3.93]; p = .59), paravalvular regurgitation ≥ 2 (0.33[0-6.28]; p = .46), or pacemaker implantation (0.84 [0.25-2.84]; p = .77) CONCLUSION: RDAVR was associated with better 2-year outcomes than TAVR in intermediate-risk patients with severe symptomatic AS.
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http://dx.doi.org/10.1111/jocs.15483DOI Listing
June 2021

HeartMate II thrombosis treated without explantation in the waiting period for heart transplantation: a case report.

Eur Heart J Case Rep 2021 Feb 25;5(2):ytaa509. Epub 2020 Dec 25.

Département d'Anesthésie-Réanimation, Université Aix-Marseille, CHU Timone, Marseille, France.

Background: The HeartMate II (HMII) is a high speed, axial flow, rotary blood pump that restores systemic flow by draining blood from the left ventricular (LV) apex and ejecting into the aortic root. This LV assist device was previously used in patients with medically refractory advanced-stage heart failure, for both destination therapy and bridge to transplantation until the introduction of HeartMate III.

Case Summary: We report herein a case of a 25-year-old patient with Interagency Registry for Mechanical Assisted circulatory 3 profile implanted with HMII device for an end-stage dilated cardiomyopathy, who experienced a pump thrombosis despite a well-conducted anticoagulant protocol. A thrombophilia with heterozygous mutation of factor II and V was diagnosed at that time. We chose to stop the device without explantation until heart transplantation.

Discussion: Pump thrombosis with HMII is associated with a prohibitive risk of morbidity and mortality. Pump thrombosis is suspected when haemolysis or congestive heart failure occurs, also in cases of overconsumption of pump power (>10 W). Pump thrombosis treatment is challenging in the case of clotting factors mutation. Pump exchange could be ineffective, exposing the patient to the recurrence of thrombo-embolic events. Intravenous thrombolysis may be used for patients not candidates for redo procedures but could be unsuccessful and expose patients to high bleeding risk. Heart transplantation remains a reliable option. In our case, pump explantation was considered too hazardous by the heart team due to a prohibitive risk of redo surgery. Then, we decided to turn off the HMII pump after the introduction of continuous intravenous dobutamine support. The haemodynamic stability allowed us to wait for heart transplantation in favourable conditions.
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http://dx.doi.org/10.1093/ehjcr/ytaa509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873806PMC
February 2021

Prosthesis-patient mismatch is an independent predictor of congestive heart failure after transcatheter aortic valve replacement.

Arch Cardiovasc Dis 2021 Jan 25. Epub 2021 Jan 25.

Department of Cardiac Surgery, La Timone Hospital, 264, rue Saint-Pierre, 13005 Marseille, France.

Background: Little is known about the effect of prosthesis-patient mismatch (PPM) on outcomes after transcatheter aortic valve replacement. We reported previously an increased risk of PPM with the SAPIEN 3 transcatheter heart valve (S3-THV).

Aims: To investigate the association of PPM with 1-year outcomes in patients with severe aortic stenosis (AS) implanted with S3-THV.

Methods: Moderate PPM was defined by an indexed effective orifice area (iEOA)≤0.85cm/m, and severe PPM by an iEOA<0.65cm/m. Inclusion criteria were severe symptomatic AS and implantation with S3-THV. The primary endpoint was hospitalization for congestive heart failure (CHF) at 1 year; the secondary endpoint was all-cause mortality.

Results: A total of 208 consecutive patients were included between 2016 and 2018. Male sex was prevalent (53.8%), mean age was 81.9±6.2 years, mean EuroSCORE II was 4.35±3.37, mean LVEF was 57.9±13%. Moderate and severe PPM were observed in 69 (33.2%) and 10 (4.8%) patients. Patients with PPM were younger (80.4±7 vs 82.8±5.41 years; P=0.006), had a larger BSA (1.84±0.19 vs 1.77±0.19 m; P=0.01), a lower iEOA (0.73±0.08 vs 1.11±0.22 cm/m; P<0.001) and a higher mean gradient (14±4.6 vs 11.9±3.9mmHg; P<0.001). CHF occurred in 16.5% vs 7% (P=0.03). By multivariable analysis, PPM was independently associated with CHF (hazard ratio [HR] 3.17, 95% confidence interval [CI] 1.17 to 8.55; P=0.032), especially in patients with mitral regurgitation≥2/4 (HR>100, 95%CI>100 to>1000; P<0.01). PPM did not correlate with all-cause mortality (HR 0.90, 95%CI 0.22 to 3.03; P=0.86).

Conclusions: PPM after S3-THV implantation is strongly associated with CHF at 1 year, but is not correlated with overall mortality.
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http://dx.doi.org/10.1016/j.acvd.2020.11.005DOI Listing
January 2021

Identification of a peripheral blood gene signature predicting aortic valve calcification.

Physiol Genomics 2020 12 12;52(12):563-574. Epub 2020 Oct 12.

Intercellular Signaling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.

Calcific aortic valve disease (CAVD) is a significant cause of illness and death worldwide. Identification of early predictive markers could help optimize patient management. RNA-sequencing was carried out on human fetal aortic valves at gestational , , and and on a case-control study with adult noncalcified and calcified bicuspid and tricuspid aortic valves. In dimension reduction and clustering analyses, diseased valves tended to cluster with fetal valves at rather than normal adult valves, suggesting that part of the disease program might be due to reiterated developmental processes. The analysis of groups of coregulated genes revealed predominant immune-metabolic signatures, including innate and adaptive immune responses involving lymphocyte T-cell metabolic adaptation. Cytokine and chemokine signaling, cell migration, and proliferation were all increased in CAVD, whereas oxidative phosphorylation and protein translation were decreased. Discrete immune-metabolic gene signatures were present at fetal stages and increased in adult controls, suggesting that these processes intensify throughout life and heighten in disease. Cellular stress response and neurodegeneration gene signatures were aberrantly expressed in CAVD, pointing to a mechanistic link between chronic inflammation and biological aging. Comparison of the valve RNA-sequencing data set with a case-control study of whole blood transcriptomes from asymptomatic individuals with early aortic valve calcification identified a highly predictive gene signature of CAVD and of moderate aortic valve calcification in overtly healthy individuals. These data deepen and broaden our understanding of the molecular basis of CAVD and identify a peripheral blood gene signature for the early detection of aortic valve calcification.
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http://dx.doi.org/10.1152/physiolgenomics.00034.2020DOI Listing
December 2020

Transcatheter Valve-in-Valve Aortic Valve Replacement as an Alternative to Surgical Re-Replacement.

J Am Coll Cardiol 2020 08;76(5):489-499

Service de Cardiologie, Centre Hospitalier Trousseau, Tours, France.

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.
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http://dx.doi.org/10.1016/j.jacc.2020.06.010DOI Listing
August 2020

Valve-in-valve transcatheter aortic valve implantation after failed surgically implanted aortic bioprosthesis versus native transcatheter aortic valve implantation for aortic stenosis: Data from a nationwide analysis.

Arch Cardiovasc Dis 2021 Jan 10;114(1):41-50. Epub 2020 Jun 10.

Service de cardiologie, CHU Trousseau, 37044 Tours, France; EA7505, université de Tours, 37044 Tours, France.

Background: Valve-in-valve transcatheter aortic valve implantation (TAVI) has emerged as a treatment for aortic bioprosthesis failure in case of prohibitive risk for redo surgery. However, clinical evaluation of valve-in-valve TAVI remains limited by the number of patients analysed.

Aim: To evaluate outcomes of valve-in-valve TAVI compared with native aortic valve TAVI at a nationwide level in France.

Methods: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients treated with TAVI for aortic stenosis or with isolated valve-in-valve TAVI for aortic bioprosthesis failure between 2010 and 2019. Propensity score matching was used for the analysis of outcomes.

Results: A total of 44,218 patients were found in the database. After matching on baseline characteristics, 2749 patients were analysed in each arm. At 30 days, no significant differences were observed regarding the occurrence of major clinical events (composite of cardiovascular mortality, all-cause stroke, myocardial infarction, major or life-threatening bleeding and conversion to open heart surgery) (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.68-1.01; P=0.32). During follow-up (mean 516 days), the combined endpoint of cardiovascular death, all-cause stroke or rehospitalization for heart failure was not different between the valve-in-valve TAVI and native TAVI groups (RR 1.03, 95% CI 0.94-1.13; P=1.00).

Conclusion: We observed that valve-in-valve TAVI was associated with good short- and long-term outcomes. No significant differences were observed compared with native valve TAVI regarding clinical follow-up.
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http://dx.doi.org/10.1016/j.acvd.2020.04.005DOI Listing
January 2021

Durability of bioprosthetic aortic valves in patients under the age of 60 years - rationale and design of the international INDURE registry.

J Cardiothorac Surg 2020 May 27;15(1):119. Epub 2020 May 27.

Cardiac Surgery, European Hospital, Rome, Italy.

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).
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http://dx.doi.org/10.1186/s13019-020-01155-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251702PMC
May 2020

Management of low blood pressure in ambulatory heart failure with reduced ejection fraction patients.

Eur J Heart Fail 2020 08 30;22(8):1357-1365. Epub 2020 Apr 30.

Faculté de Médecine, Université de Lorraine, Centre d'Investigations Cliniques Plurithématique 1433, Institut Lorrain du Cœur et des Vaisseaux, Vandoeuvre les Nancy France Groupe choc, INSERM U1116, Vandoeuvre les Nancy, France.

Low blood pressure is common in patients with heart failure and reduced ejection fraction (HFrEF). While spontaneous hypotension predicts risk in HFrEF, there is only limited evidence regarding the relationship between hypotension observed during heart failure (HF) drug titration and outcome. Nevertheless, hypotension (especially orthostatic hypotension) is an important factor limiting the titration of HFrEF treatments in routine practice. In patients with signs of shock and/or severe congestion, hospitalization is advised. However, in the very frequent cases of non-severe and asymptomatic hypotension observed while taking drugs with a class I indication in HFrEF, European and US guidelines recommend maintaining the same drug dosage. In instances of symptomatic or severe persistent hypotension (systolic blood pressure < 90 mmHg), it is recommended to first decrease blood pressure reducing drugs not indicated in HFrEF as well as the loop diuretic dose in the absence of associated signs of congestion. Unless the management of hypotension appears urgent, a HF specialist should then be sought rather than stopping or decreasing drugs with a class I indication in HFrEF. If symptoms or severe hypotension persist, no recommendations exist. Our HF group reviewed available evidence and proposes certain steps to follow in such situations in order to improve the pharmacological management of these patients.
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http://dx.doi.org/10.1002/ejhf.1835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540603PMC
August 2020

Piezo1 is required for outflow tract and aortic valve development.

J Mol Cell Cardiol 2020 06 3;143:51-62. Epub 2020 Apr 3.

Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM LabEx ICST, Montpellier, France. Electronic address:

Aims: During embryogenesis, the onset of circulatory blood flow generates a variety of hemodynamic forces which reciprocally induce changes in cardiovascular development and performance. It has been known for some time that these forces can be detected by as yet unknown mechanosensory systems which in turn promote cardiogenic events such as outflow tract and aortic valve development. PIEZO1 is a mechanosensitive ion channel present in endothelial cells where it serves to detect hemodynamic forces making it an ideal candidate to play a role during cardiac development. We sought to determine whether PIEZO1 is required for outflow tract and aortic valve development.

Methods And Results: By analysing heart development in zebrafish we have determined that piezo1 is expressed in the developing outflow tract where it serves to detect hemodynamic forces. Consequently, disrupting Piezo1 signalling leads to defective outflow tract and aortic valve development and indicates this gene may be involved in the etiology of congenital heart diseases. Based on these findings, we analysed genomic data generated from patients who suffer from left ventricular outflow tract obstructions (LVOTO) and identified 3 probands who each harboured potentially pathogenic variants in PIEZO1. Subsequent in vitro and in vivo assays indicates that these variants behave as dominant negatives leading to an inhibition of normal PIEZO1 mechanosensory activity. Expressing these dominant negative PIEZO1 variants in zebrafish endothelium leads to defective aortic valve development.

Conclusion: These data indicate that the mechanosensitive ion channel piezo1 is required for outflow tract and aortic valve development.
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http://dx.doi.org/10.1016/j.yjmcc.2020.03.013DOI Listing
June 2020

Outcomes in nonagenarians undergoing transcatheter aortic valve implantation: a nationwide analysis.

EuroIntervention 2020 Apr;15(17):1489-1496

Cardiologie, CHU-Timone, Marseille, France.

Aims: The aim of this study was to describe the midterm outcomes in nonagenarians undergoing transcatheter aortic valve implantation (TAVI).

Methods And Results: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients with aortic stenosis (AS), and specifically those treated with TAVI between 2010 and 2018. Cox regression was used for the analysis of predictors of events. We compared patients according to their age. Within the studied period, 71,095 patients older than 90 years with AS were identified. After matching on baseline characteristics, TAVI was associated with lower rates of a combined outcome of all-cause death, rehospitalisation for heart failure and stroke (relative risk [RR] 0.58, p<0.001) in comparison with matched nonagenarians with AS treated medically. During follow-up (median 161 days, interquartile range 13-625), the combined outcome occurred more frequently in nonagenarians (RR 1.22, p<0.01) who had a TAVI than in younger patients undergoing this procedure. All-cause death was reported in 17.6% versus 14.5% of nonagenarians, rehospitalisation for heart failure in 21.3% versus 18.2%, and stroke in 3.7% versus 2.9% (p<0.01 for all parameters). We identified the Charlson comorbidity index, heart failure, atrial fibrillation, stroke, vascular disease, cognitive impairment and denutrition as independent predictors of adverse outcomes in nonagenarians undergoing TAVI.

Conclusions: Among nonagenarians with AS, patients treated with TAVI had a lower risk of cardiovascular events than matched patients treated medically. The patients undergoing a TAVI at this age were often highly selected; the procedure was associated with acceptable long-term outcomes.
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http://dx.doi.org/10.4244/EIJ-D-19-00647DOI Listing
April 2020

Valve hemodynamic performance and myocardial strain after implantation of a third-generation, balloon-expandable, transcatheter aortic valve.

Cardiol J 2020 20;27(6):789-796. Epub 2019 May 20.

University Hospital Ramon y Cajal, Cardiology Department, Carreta de Colmenar Viejo, 28034 Madrid, Spain.

Background: Left ventricular (LV) mechanics are impaired in patients with severe aortic stenosis (AS); however, transcatheter aortic valve implantation (TAVI) may positively affect LV mechanics. Assessed herein is the performance of the SAPIEN 3 transcatheter heart valve (THV) and the effect of TAVI on LV function recovery, as assessed by global longitudinal strain (GLS).

Methods: A subset of patients from the SOURCE 3 registry (n = 276) from 16 European centers received SAPIEN 3 balloon-expandable THV. Echocardiography was performed at baseline, postprocedure, and at 1 year, including assessment of GLS using standard two-dimensional images, and was analyzed in a core laboratory. Paired analyses between baseline and discharge, baseline and at 1 year were conducted.

Results: Hemodynamic parameters were improved after TAVI and sustained to 1 year. At 1 year, the rate of moderate to severe paravalvular leaks (PVL), and moderate to severe mitral and tricuspid regurgitations were 1.8%, 1.7%, and 8.0%, respectively. The discharge GLS (-15.6 ± 5.1; p = 0.004; n = 149) improved significantly from baseline (-15.1 ± 4.8) following TAVI. This improvement was sustained at 1 year compared with baseline (-17.0 ± 4.6, p < 0.001; n = 100). Conversely, LV ejection fraction (LVEF) did not significantly change following TAVI (p = 0.47).

Conclusions: Following TAVI with a third-generation THV, valve performances were good at 1 year with low PVL rate. The LV mechanics improved immediately after the procedure and were maintained at 1 year. These findings demonstrate the benefit of TAVI on LV mechanics, and suggests that GLS may be superior to LVEF in assessing this benefit. Clinicaltrial.gov number: NCT02698956.
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http://dx.doi.org/10.5603/CJ.a2019.0049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079106PMC
May 2019

Open-heart transcatheter aortic valve replacement in complex aortic valve reoperation: about a case series.

Eur Heart J Case Rep 2018 Jun 24;2(2):yty064. Epub 2018 May 24.

Department of Cardiac Surgery, La Timone Hospital, Marseille, 264 rue Saint Pierre, Marseille, France.

Introduction: Aortic homograft and stentless aortic root are helpful in acute infective endocarditis of the aortic valve as biological conduit when total root replacement is required. Reoperation for failure of aortic homograft and stentless aortic root remains challenging for the surgeon as the entire root can be heavily calcified.

Case Presentation: Here, are reported, three cases of patients successfully treated with open-heart transcatheter aortic valve replacement (TAVR) whereas no other prosthesis was implantable due to a massively calcified homograft or stentless prosthesis.

Discussion: Open-heart TAVR avoided the risk of complete root replacement which is higher than redo aortic valve replacement (AVR). This rescue technique facilitated risky surgical procedure by combining the strengths of both TAVR and conventional AVR.
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http://dx.doi.org/10.1093/ehjcr/yty064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177095PMC
June 2018

Long-Term Implications of Atrial Fibrillation in Patients With Degenerative Mitral Regurgitation.

J Am Coll Cardiol 2019 01;73(3):264-274

Cardiovascular Division, Mayo Clinic, Mayo Medical School, Rochester, Minnesota.

Background: Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery.

Objectives: This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term.

Methods: Patients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed.

Results: Among 2,425 patients (age 67 ± 13 years; 71% male, 67% asymptomatic, ejection fraction 64 ± 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 ± 1%, 59 ± 3%, and 46 ± 2%, respectively; p < 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values <0.0001). Surgery (n = 1,889, repair 88%) was associated with better survival versus medical management, regardless of all baseline characteristics and rhythm (adjusted hazard ratio: 0.26; 95% confidence interval: 0.23 to 0.30; p < 0.0001) but post-surgical outcome remained affected by AF (10-year post-surgical survival in SR and in paroxysmal and persistent AF was 82 ± 1%, 70 ± 4%, and 57 ± 3%, respectively; p < 0.0001).

Conclusions: AF is a frequent occurrence at DMR diagnosis. Although AF is associated with older age and more severe presentation of DMR, it is independently associated with excess mortality long-term after diagnosis. Surgery is followed by improved survival in each cardiac rhythm subset, but persistence of excess risk is observed for each type of AF. Our study indicates that detection of AF, even paroxysmal, should trigger prompt consideration for surgery.
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http://dx.doi.org/10.1016/j.jacc.2018.10.067DOI Listing
January 2019

Long-term results of surgical treatment of secondary severe mitral regurgitation in patients with end-stage heart failure: Advantage of prosthesis insertion.

Arch Cardiovasc Dis 2019 Feb 29;112(2):95-103. Epub 2018 Dec 29.

Department of Cardiology, La Timone Hospital, AP-HM, 13005 Marseille, France. Electronic address:

Background: Surgical treatment of secondary mitral regurgitation (SMR) is controversial.

Aim: To analyse outcome after undersizing annuloplasty (UA) and mitral valve replacement (MVR).

Methods: Consecutive patients operated on for severe SMR, with left ventricular ejection fraction (LVEF)<40% and refractory CHF, were included. Endpoints were in-hospital mortality, mid-term cardiovascular (CV) mortality, evolution of LV variables and recurrence of mitral regurgitation (MR).

Results: 59 patients were included (mean age 65±10 years, preoperative LVEF 36±6%; effective regurgitant orifice [ERO] 41±17 mm), 41 with ischaemic disease: 12 underwent UA and 47 underwent MVR; only eight had concomitant coronary revascularization. In-hospital mortality was 3.3% (8.3% in UA group; 2.1% in MVR group). Eight-year CV mortality was 39±13% (40±18% in UA group; 27±10% in MVR group). Older age (hazard ratio 1.14, 95% confidence interval 1.07 to 1.22; P<0.001) and LV end-systolic diameter (hazard ratio 1.18, 95% confidence interval 1.09 to 1.27; P<0.001) independently predicted CV mortality. LVEF did not change between the preoperative and follow-up transthoracic echocardiograms in the MVR group (36±6% vs. 35±10%; P=0.6) or the UA group (36±5% vs. 31±12%; P=0.09). Conversely, LV end-diastolic diameter decreased significantly in the MVR group (64±8m to 59±9mm; P=0.002), but not in the UA group (61±7m to 64±10mm; P=0.2). Recurrence of significant MR occurred in 81% of patients in the UA group (mean postoperative ERO 19±6 mm) versus none in the MVR group.

Conclusions: Surgical treatment of SMR can be performed with acceptable operative risk and mid-term survival in severe heart failure, even if there is no indication for revascularization. MVR is associated with significant reverse remodelling, and UA with prohibitive risk of MR recurrence.
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http://dx.doi.org/10.1016/j.acvd.2018.09.006DOI Listing
February 2019

Transoesophageal echocardiography current practice in France: A multicentre study.

Arch Cardiovasc Dis 2018 Dec 4;111(12):730-738. Epub 2018 Jul 4.

Department of cardiology, SOS Endocardites, Henri-Mondor Hospital, 94010 Creteil, France.

Background: Few data are available on the application of transoesophageal echocardiography (TOE) recommendations in daily practice.

Aims: To evaluate TOE practice based on echocardiography societies' guidelines, and to determine complication rates and factors associated with patient feelings.

Methods: Between April and June 2017, we prospectively included all consecutive patients referred to 14 French hospitals for a transoesophageal echocardiogram (TOE). A survey was taken just after the examination, which included questions about pre-procedural anxiety, and any pain, unpleasant feeling or breathing difficulties experienced during the examination.

Results: Overall, 1718 TOEs were performed, mainly for stroke evaluation. A standardized operating procedure checklist was completed in half of the patients before the examination. TOE was unpleasant for 62.4% of patients, but was stopped for agitation or intolerance in 3.5 and 1.4% of cases, respectively. We observed one severe complication (pulmonary oedema). The mean TOE duration was short (9.2±4.6minutes), but was longer with residents than with more experienced physicians (11±4.7 vs. 8.8±4.7minutes for junior physicians [P=0.0027]; vs. 8.9±4.8minutes for senior physicians [P=0.0013]; and vs. 7.5±4.1minutes for associate professors/professors [P<0.0001]). The visual analogue scale (VAS) score after TOE was good (8.3±1.7 out of 10), and was better in patients with general anaesthesia (GA) than in those without GA (9.3±0.9 vs. 8.1±1.7; P<0.0001). In patients without GA, the VAS score was similar with and without local anaesthesia (8.1±1.7 vs. 8.2±1.6; P=0.19). After multivariable adjustment, absence of anxiety before TOE and greater operator experience were consistently associated with a higher VAS score.

Conclusions: TOE is safe, with a low rate of complications and few stops for intolerance. A shorter TOE duration and better patient feelings were observed for experienced operators, highlighting the importance of the learning curve, and paving the way for teaching on a TOE simulator.
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http://dx.doi.org/10.1016/j.acvd.2018.03.014DOI Listing
December 2018

Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: A randomised controlled clinical trial.

Eur J Anaesthesiol 2018 12;35(12):911-918

From the Department of Anaesthesia and Intensive Care Medicine (DL, LN, FK, NB, LV, CG), Department of Biochemistry (RG, EF), Department of Biostatistics (NR, RG), Department of Cardiac Surgery (AT, DG, VG), La Timone University Hospital, Aix-Marseille University, Marseille, France (FC).

Background: Raised plasma levels of endogenous adenosine after cardiac surgery using cardiopulmonary bypass (CPB) have been related to the incidence of postoperative atrial fibrillation (POAF).

Objective: We wished to assess if caffeine, an adenosine receptor antagonist could have a beneficial effect on the incidence of POAF.

Design: A randomised controlled study.

Setting: Single University Hospital.

Patients: One hundred and ten patients scheduled for heart valve surgery with CPB.

Interventions: We randomly assigned patients to receive peri-operative oral caffeine (400 mg every 8 h for 2 days) or placebo. Adenosine plasma concentrations and caffeine pharmacokinetic profile were evaluated in a subgroup of 50 patients.

Main Outcome Measures: The primary endpoint was the rate of atrial fibrillation during postoperative hospital stay.

Results: The current study was stopped for futility by the data monitoring board after an interim analysis. The incidence of atrial fibrillation was similar in the caffeine and in the placebo group during hospital stay (33 vs. 29%, P = 0.67) and the first 3 postoperative days (18 vs. 15%; P = 0.60). Basal and postoperative adenosine plasma levels were significantly associated with the primary outcome. Adenosine plasma levels were similar in the two treatment groups. Caffeine administration was associated with a higher incidence of postoperative nausea and vomiting (27 vs. 7%, P = 0.005).

Conclusion: Oral caffeine does not prevent POAF after heart valve surgery with CPB but increased the incidence of postoperative nausea and vomiting.

Clinical Trial Registration: ClinicalTrials.gov, no.: NCT01999829.
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http://dx.doi.org/10.1097/EJA.0000000000000824DOI Listing
December 2018

Marseille scoring system for empiric treatment of infective endocarditis.

Eur J Clin Microbiol Infect Dis 2018 May 3;37(5):841-849. Epub 2018 Feb 3.

URMITE, Aix Marseille Université, UM63, CNRS 7278, IRD 198, INSERM 1095, AP-HM, URMITE, IHU - Méditerranée Infection, 9-21 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.

Despite advances in medical, surgical, and critical care, infective endocarditis (IE) remains associated with considerable morbidity and mortality. We evaluated the performance of the Marseille score, including clinical data and biological tests obtained within 2 h, to identify patients at high risk of IE in order to initiate early antimicrobial treatment. This was secondarily confirmed using modified ESC criteria combined with molecular testing and fluorodeoxyglucose-positron emission tomography/computed tomography as diagnostic tools. In a prospective cohort study, we enrolled 484 patients with cardiovascular predisposition and clinical suspicion of IE from 2011 to 2013. The final diagnosis was definite IE in 123 patients and possible IE in 107. Marseille score was calculated adding one point for each present parameter (range 0-9). This score includes clinical, epidemiological (male, fever, splenomegaly, clubbing, vascular disease and stroke) and biological criteria (Leucocytes >10,000/mm3, sedimentation rate (SR) > 50/mm or C reactive protein >10 mg/L and hemoglobin <100 g/l). A score of 2 or more performed best in predicting IE in patients with predisposing heart lesions. Sensitivity was better on left-side heart lesions (94%) than on right-side heart lesions (85%) (p = 0.04) and better for valvulopathy (94%) than intra cardiac devices (84%) (p = 0.02). The predictive positive value of prosthetic valves was greater than that of native valves (p = 0.02). Using our simple Marseille score combined with our standardized diagnostic procedures would help improve IE management by focusing on early empiric treatment within 2 h of admission for patients with cardiac predisposition factors.
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http://dx.doi.org/10.1007/s10096-017-3177-3DOI Listing
May 2018

The MIDA Mortality Risk Score: development and external validation of a prognostic model for early and late death in degenerative mitral regurgitation.

Eur Heart J 2018 04;39(15):1281-1291

Mayo Clinic, Division of Cardiovascular Disease, Mayo Medical School, 200 First St. SW. Rochester, MN 55905, USA.

Aims: In degenerative mitral regurgitation (DMR), lack of mortality scores predicting death favours misperception of individual patients' risk and inappropriate decision-making.

Methods And Results: The Mitral Regurgitation International Database (MIDA) registries include 3666 patients (age 66 ± 14 years; 70% males; follow-up 7.8 ± 5.0 years) with pure, isolated, DMR consecutively diagnosed by echocardiography at tertiary (European/North/South-American) centres. The MIDA Score was derived from the MIDA-Flail-Registry (2472 patients with DMR and flail leaflet-Derivation Cohort) by weighting all guideline-provided prognostic markers, and externally validated in the MIDA-BNP-Registry (1194 patients with DMR and flail leaflet/prolapse-Validation Cohort). The MIDA Score ranged from 0 to 12 depending on accumulating risk factors. In predicting total mortality post-diagnosis, the MIDA Score showed excellent concordance both in Derivation Cohort (c = 0.78) and Validation Cohort (c = 0.81). In the whole MIDA population (n = 3666 patients), 1-year mortality with Scores 0, 7-8, and 11-12 was 0.4, 17, and 48% under medical management and 1, 7, and 14% after surgery, respectively (P < 0.001). Five-year survival with Scores 0, 7-8, and 11-12 was 98 ± 1, 57 ± 4, and 21 ± 10% under medical management and 99 ± 1, 82 ± 2, and 57 ± 9% after surgery (P < 0.001). In models including all guideline-provided prognostic markers and the EuroScoreII, the MIDA Score provided incremental prognostic information (P ≤ 0.002).

Conclusion: The MIDA Score may represent an innovative tool for DMR management, being able to position a given patient within a continuous spectrum of short- and long-term mortality risk, either under medical or surgical management. This innovative prognostic indicator may provide a specific framework for future clinical trials aiming to compare new technologies for DMR treatment in homogeneous risk categories of patients.
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http://dx.doi.org/10.1093/eurheartj/ehx465DOI Listing
April 2018

Reduced aggrecan expression affects cardiac outflow tract development in zebrafish and is associated with bicuspid aortic valve disease in humans.

Int J Cardiol 2017 Dec 24;249:340-343. Epub 2017 Sep 24.

IGF, LabexICST, CNRS, INSERM, Univ Montpellier, Montpellier, France. Electronic address:

Hemodynamic forces have been known for a long time to regulate cardiogenic processes such as cardiac valve development. During embryonic development in vertebrates, the outflow tract (OFT) adjacent to the ventricle comes under increasing hemodynamic load as cardiogenesis proceeds. Consequently, extracellular matrix components are produced in this region as the cardiac cushions form which will eventually give rise to the aortic valves. The proteoglycan AGGRECAN is a key component of the aortic valves and is frequently found to be deregulated in a variety of aortic valve diseases. Here we demonstrate that aggrecan expression in the OFT of developing zebrafish embryos is hemodynamically dependent, a process presumably mediated by mechanosensitive channels. Furthermore, knockdown or knockout of aggrecan leads to failure of the OFT to develop resulting in stenosis. Based on these findings we analysed the expression of AGGRECAN in human bicuspid aortic valves (BAV). We found that in type 0 BAV there was a significant reduction in the expression of AGGRECAN. Our data indicate that aggrecan is required for OFT development and when its expression is reduced this is associated with BAV in humans.
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http://dx.doi.org/10.1016/j.ijcard.2017.09.174DOI Listing
December 2017

Pulmonary cyst embolism: a rare complication of hydatidosis.

Eur J Cardiothorac Surg 2018 Jan;53(1):286-287

Department of Cardiac Surgery, La Timone Hospital, Marseille, France.

Hydatid disease is an endemic parasitosis that results from the ingestion of echinococcosis tapeworm eggs. This condition leads to the formation of cysts, mainly in the liver and lungs, and causes life-threatening complications. Cardiac involvement represents only 0.5-2% of the localizations. We report a rare case of a pulmonary cyst embolism that required emergency surgical intervention.
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http://dx.doi.org/10.1093/ejcts/ezx286DOI Listing
January 2018

Diagnosis of Infective Endocarditis After TAVR: Value of a Multimodality Imaging Approach.

JACC Cardiovasc Imaging 2018 01 16;11(1):143-146. Epub 2017 Aug 16.

Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, Aix-Marseille Université-UM63, Centre National de la Recherche Scientifique 7278, IRD 198, Institut National de la Santé et de la Recherche Médicale 1095-IHU-Méditerranée Infection, Marseille, France.

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http://dx.doi.org/10.1016/j.jcmg.2017.05.016DOI Listing
January 2018

Rapid-deployment aortic valve replacement for severe aortic stenosis: 1-year outcomes in 150 patients.

Interact Cardiovasc Thorac Surg 2017 07;25(1):68-74

Department of Cardiac Surgery, La Timone Hospital, Marseille, France.

Objectives: This study aimed to evaluate the safety and effectiveness of rapid-deployment aortic valve replacement (RDAVR) for severe aortic stenosis (AS).

Methods: All consecutive patients with severe AS who underwent RDAVR with the EDWARDS INTUITY bioprosthesis were prospectively included in a single-centre, cohort study between July 2012 and April 2015. Clinical examination and transthoracic echocardiography were performed preoperatively and at 1-month and 1-year follow-up.

Results: We included 150 patients: mean age 76.8 ± 6.2 years, 68.7% male and mean EuroSCORE II 3.4 ± 3.7%. Implantation was successful in all: 103 (68.7%) had isolated aortic valve replacement (AVR) and 47 (31.3%) had concomitant procedures. For isolated AVR, mean cross-clamp and cardiopulmonary bypass times were 37.6 ± 13.3 and 59.9 ± 20.4 min, respectively. Overall, the 1-year Kaplan-Meier survival rate was 97.1% (95% confidence interval 92.4-98.9%). At 1 year, stroke occurred in 5 patients (3.34%), myocardial infarction in 1 (0.69%), endocarditis in 1 (0.69%), early explantation in 1 (0.67%), pacemaker implantation in 8 (5.6%) and Grade 2 periprosthetic regurgitation in 4 (3.2%; no grade 3 of 4). There were significant decreases from baseline ( P  < 0.001) in the proportion at New York Heart Association Class III/V (35.3-4.1%), mean gradient (54.9 ± 17.3 mmHg to 11.3 ± 4.8 mmHg) and mean left ventricular mass index (160.3 ± 44.8 g/m 2 to 118.5 ± 39.4 g/m 2 ). Mean indexed effective orifice area at 1 year was 1.02 ± 0.37 cm 2 /m 2 . Ten patients (6.6%) had severe patient-prosthesis mismatch.

Conclusions: RDAVR for severe AS provided favourable outcomes over 1 year.
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http://dx.doi.org/10.1093/icvts/ivx050DOI Listing
July 2017

Patient-prosthesis mismatch in new generation trans-catheter heart valves: a propensity score analysis.

Eur Heart J Cardiovasc Imaging 2018 02;19(2):225-233

Department of Cardiac Surgery, La Timone Hospital, La Timone Hospital 264, rue saint Pierre 13005 Marseille, France.

Aims: When compared with the former Sapien XT (XT-THV), the Sapien 3 trans-catheter heart valve (S3-THV) embeds an outer annular sealing cuff to prevent para-valvular regurgitation (PVR). The consequences of this new feature on valve haemodynamics have never been evaluated. We aimed to compare both types of prostheses regarding patient-prosthesis mismatch (PPM).

Methods And Results: Patients who underwent a TAVR for aortic stenosis were retrospectively included. Regression adjustment for the propensity score was used to compare 50 XT-THV patients with 71 S3-THV. At the 1-month follow-up, the mean indexed effective orifice area (iEOA) was 1.12 ± 0.34 cm2/m2 with XT-THV and 0.96 ± 0.27 cm2/m2 with S3-THV. The mean gradient was 11 ± 5 mmHg and 13 ± 5 mmHg, respectively. Nine patients had moderate PPM, and two exhibited severe PPM with XT-THV. Nineteen patients had moderate PPM, and seven demonstrated severe PPM with S3-THV. There was a five-fold increased risk of PPM with S3-THV (OR = 4.98; [1.38-20.94], P = 0.019). S3-THV decreased the iEOA by 0.21 cm2/m2 [-0.21; (-0.38 to - 0.05); P = 0.012] and increased the mean gradient by 4.95 mmHg [4.95; (2.27-7.64); P < 0.001]. The risk of PPM was increased 15.24-fold with 23 mm S3-THV [15.24; (2.92-101.52); P = 0.002] in comparison with the 23 mm XT-THV. PVR were reduced by 98% with S3-THV.

Conclusion: There is an increased risk of PPM with 23mm S3-THV in comparison with 23 mm XT-THV. This may be attributable to the additional sub-annular cuff that avoids the risk of PVR. Regarding the increased vulnerability of younger patients to PPM, we provide essential information on the extension of TAVR indication to the younger population.
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http://dx.doi.org/10.1093/ehjci/jex019DOI Listing
February 2018

Severe right ventricular dysfunction is an independent predictor of pre- and post-transplant mortality among candidates for heart transplantation.

Arch Cardiovasc Dis 2017 Mar 20;110(3):139-148. Epub 2017 Jan 20.

Department of Cardiac Surgery, La Timone Hospital, 13005 Marseille, France.

Background: Heart transplantation is the gold-standard treatment for end-stage heart failure. However, the shortage of grafts has led to longer waiting times and increased mortality for candidates without priority.

Aims: To study waiting-list and post-transplant mortality, and their risk factors among patients registered for heart transplantation without initial high emergency procedure.

Methods: All patients registered on the heart transplantation waiting list (2004-2015) without initial high emergency procedure were included. Clinical, biological, echocardiographic and haemodynamic data were collected. Waiting list and 1-year post-transplant survival were analysed with a Kaplan-Meier model.

Results: Of 221 patients enrolled, 168 (76.0%) were men. Mean age was 50.0±12.0 years. Forty-seven patients died on the waiting list, resulting in mortality rates of 11.2±2.7% at 1 year, 31.9±5.4% at 2 years and 49.4±7.1% at 3 years. Median survival was 36.0±4.6 months. In the multivariable analysis, left ventricular ejection fraction<30% (hazard ratio [HR]: 3.76, 95% confidence interval [CI]: 1.38-10.24; P=0.010) and severe right ventricular systolic dysfunction (HR: 2.89, 95% CI: 1.41-5.92; P=0.004) were associated with increased waiting-list mortality. The post-transplant survival rate was 73.1±4.4% at 1 year. Pretransplant severe right ventricular dysfunction and age>50 years were strong predictors of death after transplantation (HR: 5.38, 95% CI: 1.38-10.24 [P=0.020] and HR: 6.16, 95% CI: 1.62-9.32 [P=0.0130], respectively).

Conclusions: Mortality among candidates for heart transplantation remains high. Patients at highest risk of waiting-list mortality have to be promoted, but without compromising post-transplant outcomes. For this reason, candidates with severe right ventricular dysfunction are of concern, because, for them, transplantation is hazardous.
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http://dx.doi.org/10.1016/j.acvd.2016.06.002DOI Listing
March 2017

Cross-Reactivity Between Heparin and Danaparoid Antibodies in Cardiac Surgery.

Ann Thorac Surg 2017 Jan;103(1):e9-e10

Aix-Marseille Université, URMITE, UM63, CNRS 7278, Inserm U1095, Faculté de Médecine, Marseille, France; Laboratoire d'Hématologie, C.H.U. La Timone, APHM, Marseille, France. Electronic address:

Management of heparin-induced thrombocytopenia (HIT) entails cessation of heparin and initiation of a nonheparin parenteral anticoagulant such as danaparoid. Danaparoid cross-reactivity with HIT antibodies is an uncommon complication of treatment of HIT. We report the case of confirmed HIT and in vivo cross-reactivity with danaparoid, complicating severe sepsis due to an infectious endocarditis treated by cardiac surgery.
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http://dx.doi.org/10.1016/j.athoracsur.2016.06.068DOI Listing
January 2017

Evaluation of empirical treatment for blood culture-negative endocarditis.

J Antimicrob Chemother 2017 01 27;72(1):290-298. Epub 2016 Sep 27.

Department of Infectious Diseases, Hôpital de la Timone, AP-HM, Aix-Marseille University, Marseille, France

Objectives: Much progress has been made in understanding the main causes of blood culture-negative endocarditis (BCNE). Few studies concerning BCNE treatment (due to previous antibiotics used or fastidious pathogens) are available. We performed this study to evaluate the effectiveness of our therapeutic protocol in BCNE, based on compliance with the protocol, outcome and 1 year mortality.

Patients And Methods: We collected prospectively and analysed retrospectively cases of BCNE between 2002 and 2014, using a simplified and standardized protocol developed by our multidisciplinary team. We apply two kinds of protocols to treat BCNE, which include only four intravenous antimicrobial agents: amoxicillin, vancomycin, gentamicin and amphotericin B.

Results: We had 177 patients with definite BCNE. There were 154 (87.0%) patients treated with both appropriate antimicrobial agents and appropriate duration of treatment. We analysed the causes of inappropriate treatment in 13 (7.3%) cases and inappropriate duration in 10 (5.6%) cases. The treatment changes were justified in all cases except one of discharge against medical advice. The fatality rate was 5.1% (nine cases) and all deaths occurred in the group of patients who were treated with appropriate treatment; however, four deaths were not attributable to empirical treatment failure. Concerning the other deaths, the lack of surgical management, in association with empirical treatment, could explain our protocol's failure, such as poorly tolerated surgery.

Conclusions: Our protocol is efficient and our mortality rate was low, compared with the literature review. This may result from a strategy that uses a sampling procedure and a standardized protocol at the same time.
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http://dx.doi.org/10.1093/jac/dkw362DOI Listing
January 2017

Krox20 heterozygous mice: A model of aortic regurgitation associated with decreased expression of fibrillar collagen genes.

Arch Cardiovasc Dis 2016 Mar 23;109(3):188-98. Epub 2015 Dec 23.

Aix Marseille Université, GMGF UMR_S910, Faculté de Médecine, 27, boulevard Jean-Moulin, 13385 Marseille, France; Inserm, U910, Faculté de Médecine, 13385 Marseille, France. Electronic address:

Background: The mechanism involved in the onset of aortic valve (AoV) disease remains unclear despite its poor prognosis and frequency. Recently, we reported that Krox20 (EGR2 in humans) is involved in AoV development and dysfunction.

Aim: Analyze Krox20 heterozygous mice (Krox20(+/-)) to discover whether incomplete expression of Krox20 can cause valvular diseases.

Methods: Transcriptional levels of Col1a2/COL1A2 and Krox20/EGR2 in AoVs from Krox20(+/-) mice and human patients operated on for severe aortic regurgitation were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Human control valves were obtained from three transplanted patients without AoV disease. Twenty-one heterozygous Krox20(+/-) mice were compared with 35 controls at different ages. Three independent measurements of valve thickness were performed on magnified tissue sections using Image J software. In vivo valve structure and function were evaluated using the high-frequency Vevo(®) 2100 echocardiogram.

Results: qRT-PCR analysis using AoVs from patients with severe aortic regurgitation showed a decrease in EGR2 expression associated with significant downregulation of COL1A2 expression (P<0.05). Similar results were observed in the AoVs of Krox20(+/-) mice. Anatomical examination revealed that incomplete invalidation of Krox20 caused significant thickening of the aortic leaflet compared with controls (145±22 vs. 75±24μm; P=0.01). Within the mutant group, this thickening worsened significantly over time (Krox20(+/-) mice aged>7 vs.<7months: 136±48 vs. 102±41μm; P<0.001). Moreover, the aortic leaflets of embryonic day 18.5 Krox20(+/-) embryos were significantly more thickened than those from controls, suggesting that this disease begins during embryonic development. Echo-Doppler analysis showed a significant increase in AoV dysfunction in heterozygous versus control mice (53% vs. 17%; P<0.001), suggesting a tight relationship between valve architecture and function. Morphometric analysis revealed that the most severe AoV dysfunction was always associated with the most thickened valves. Classic histological analysis revealed that mutant AoVs had extracellular matrix disorganization, with features of human myxomatous degeneration, including excess of proteoglycan deposition in spongiosa and reduction of collagen fibre in fibrosa, but no calcification.

Conclusion: Decreased expression of Krox20 in mice causes degeneration of the aortic leaflets and disorganization of the extracellular matrix, causing valvular dysfunction.
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http://dx.doi.org/10.1016/j.acvd.2015.10.002DOI Listing
March 2016

An uncommon cause of tricuspid regurgitation: three-dimensional echocardiographic incremental value, surgical and genetic insights.

Eur J Cardiothorac Surg 2016 Jul 15;50(1):180-2. Epub 2015 Dec 15.

Aix Marseille Université, GMGF 13385, Marseille, France Inserm, UMR_S910, 13385 Marseille, France

Congenital tricuspid valve disease is a rare defect that includes regurgitation, stenosis and Ebstein's anomaly. We report a case of severe tricuspid regurgitation associated with functional mitral regurgitation in a 47-year-old man with congestive heart failure. Transthoracic echocardiography (TTE) ruled out any Ebstein's anomaly. Three-dimensional TTE revealed a 'tricuspid hole' into the anterior leaflet that was only attached to the tricuspid annulus next to both anteroseptal and anteroposterior commissures. There was no sign of leaflet tear or perforation. The surgical repair of the tricuspid and mitral valves was performed with an optimal result. No sign of endocarditis or rheumatic disease was observed during the intervention. Sequence analysis of GATA4, HEY2 and ZFPM2 genes was performed, but no causative mutation was identified.
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http://dx.doi.org/10.1093/ejcts/ezv423DOI Listing
July 2016

Rapid Deployment of Aortic Bioprosthesis in Elderly Patients With Small Aortic Annulus.

Ann Thorac Surg 2016 Apr 18;101(4):1434-41. Epub 2015 Nov 18.

Department of Cardiac Surgery, La Timone Hospital, Marseille, France.

Background: Aortic valve replacement in elderly patients with a small aortic annulus remains challenging. Patient-prosthesis mismatch (PPM) should be prevented without impacting operative mortality. Hemodynamic benefits resulting from rapid-deployment aortic valve replacement with the Edwards Intuity bioprosthesis for this indication were evaluated.

Methods: Elective patients with severe aortic stenosis who required an Edwards Intuity bioprosthesis, size 19 mm and 21 mm, were prospectively included between July 2012 and July 2014. Transthoracic echocardiography was performed preoperatively and at 1-month follow-up.

Results: Sixty-six consecutive patients (mean age, 78 ± 6.4 years; 54.5% women) were included. The Intuity 19 mm was inserted in 29 patients, and the Intuity 21 mm was inserted in 37 patients. No deaths or aortic annulus ruptures occurred. Mean aortic cross-clamp time was 42.7 ± 18.2 minutes. At the 1-month follow-up, mean New York Heart Association classification was 1.6 ± 0.5 versus 2.2 ± 0.8 (p < 0.001). The mean gradient decreased from 59 ± 17.6 mm Hg to 13.7 ± 4.4 mm Hg (p < 0.001). Mean indexed effective orifice area was 0.77 ± 0.17 cm(2)/m(2) for the Intuity 19 mm and 1.01 ± 0.32 cm(2)/m(2) for the Intuity 21 mm. Twenty-one patients (32%) had a moderate PPM (indexed effective orifice area < 0.85 cm(2)/m(2)), and 10 patients (15%) had a severe PPM (indexed effective orifice area < 0.65 cm(2)/m(2)). The mean gradient was 15.1 ± 3.5 mm Hg and 16.9 ± 4.9 mm Hg in the moderate PPM group and severe PPM group, respectively (p = 0.3). The left ventricular mass index dramatically decreased from 153.2 ± 32.7 g/m(2) to 118.4 ± 20.2 g/m(2) (p < 0.001), and only 1 patient (1.5%) had a periprosthetic regurgitation greater than 1.

Conclusions: Regarding the low rate of severe PPM and the early regression of left ventricular mass, these preliminary studies indicate the potential benefit of the Intuity bioprosthesis in patients with a small aortic annulus. Midterm results should be evaluated.
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http://dx.doi.org/10.1016/j.athoracsur.2015.09.024DOI Listing
April 2016