Publications by authors named "Dominique Babuty"

170 Publications

Ischemic Stroke in Patients With Hypertrophic Cardiomyopathy According to Presence or Absence of Atrial Fibrillation.

Stroke 2021 Oct 4:STROKEAHA121034213. Epub 2021 Oct 4.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L.).

Background And Purpose: Patients with hypertrophic cardiomyopathy (HCM) have high risk of ischemic stroke (IS), especially if atrial fibrillation (AF) is present. Improvements in risk stratification are needed to help identify those patients with HCM at higher risk of stroke, whether AF is present or not.

Methods: This French longitudinal cohort study from the database covering hospital care from 2010 to 2019 analyzed adults hospitalized with isolated HCM. A logistic regression model was used to construct a French HCM score, which was compared with the HCM Risk-CVA and CHADS-VASc scores using c-indexes and calibration analysis.

Results: In 32 206 patients with isolated HCM, 12 498 (38.8%) had AF, and 2489 (7.7%) sustained an IS during follow-up. AF in patients with HCM was independently associated with a higher risk for death (hazard ratio, 1.129 [95% CI, 1.088-1.172]), cardiovascular death (hazard ratio, 1.254 [95% CI, 1.177-1.337]), IS (hazard ratio, 1.210 [95% CI, 1.111-1.317]), and other major cardiovascular events. Independent predictors of IS in HCM were older age, heart failure, AF, prior IS, smoking and poor nutrition (all <0.05). For the HCM Risk-CVA score, CHADS-VASc score and a French HCM score, all c-indexes were 0.65 to 0.70, with good calibration. Among patients with AF, the CHADS-VASc score had marginal improvement over the HCM Risk-CVA score but was less predictive compared with the French HCM score (=0.001). In patients without AF, both HCM Risk-CVA score and the French HCM score had significantly better prediction compared with CHADS-VASc (both <0.0001). Decision curve analysis demonstrated that the French HCM score had the best clinical usefulness of the 3 tested risk scores.

Conclusions: Patients with HCM have a high prevalence of AF and a significant risk of IS, and the presence of AF in patients with HCM was independently associated with worse outcomes. A simple French HCM score shows good prediction of IS in patients with HCM and clinical usefulness, with good calibration.
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http://dx.doi.org/10.1161/STROKEAHA.121.034213DOI Listing
October 2021

Leadless pacemakers in critically ill patients requiring prolonged cardiac pacing: A multicenter international study.

J Cardiovasc Electrophysiol 2021 09 22;32(9):2522-2527. Epub 2021 Jul 22.

Department of Cardiology, University Hospital of Tours, Tours, France.

Background: Temporary transvenous pacing in critically ill patients requiring prolonged cardiac pacing is associated with a high risk of complications. We sought to evaluate the safety and efficacy of self-contained intracardiac leadless pacemaker (LPM) implantation in this population.

Methods And Results: Consecutive patients implanted with a Micra LPM during the hospitalization in an intensive care unit were retrospectively included. Inclusion criteria were: more than or equal to 1 supracaval central venous line, or a ventilation tube, or intravenous antibiotic therapy for ongoing sepsis or bacteremia. Patients with a history of the previous implantation of a pacemaker were excluded. Out of 1016 patients implanted with an LPM, 99 met the inclusion criteria. Mean age was 75 years and Charlson comorbidity index 7. LPM implantation was successfully performed in 98% of cases, with a perioperative complication rate of 5%, mainly cardiac injuries. In-hospital mortality rate was 6%. No late (>30 days) device-related complication occurred, especially no infection.

Conclusions: LPM appears as an acceptable alternative to conventional temporary transvenous pacing in selected critically ill patients requiring prolonged cardiac pacing, especially regarding the risk of infection.
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http://dx.doi.org/10.1111/jce.15175DOI Listing
September 2021

Outcomes associated with pacemaker implantation following transcatheter aortic valve replacement: A nationwide cohort study.

Heart Rhythm 2021 Jun 17. Epub 2021 Jun 17.

Service de Cardiologie, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Université de Tours, Tours, France.

Background: Conduction abnormalities following transcatheter aortic valve replacement (TAVR) often may require permanent pacemaker implantation (PPM).

Objective: The purpose of this study was to evaluate outcomes associated with PPM after a TAVR procedure in a large, nationwide-level population.

Methods: Based on the administrative hospital discharge database, the incidence of all-cause death, cardiovascular death, and hospitalization for heart failure (HF) were retrospectively collected, based on the presence or absence of PPM, in the first 30 days following all TAVRs in France from 2010 to 2019.

Results: Among 520,662 patients hospitalized for aortic stenosis, 49,201 were treated with TAVR. A total of 29,422 patients had follow-up ≥6 months (median 1.7 years), 22% already had PPM at baseline, and 22% underwent PPM within the first 30 days post-TAVR. Adjusted hazard ratios for the combined risk of all-cause death and hospitalization for HF, during the whole follow-up, were higher in both patients with a previous PPM and in those implanted within 30 days (hazard ratio [95% confidence interval] 1.12 [1.07-1.17] and 1.11 [1.06-1.16], respectively).

Conclusion: PPM at baseline and within 30 days post-TAVR are independently associated with higher mortality and HF hospitalization during follow-up.
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http://dx.doi.org/10.1016/j.hrthm.2021.06.1175DOI Listing
June 2021

The Defibrillation Conundrum: New Insights into the Mechanisms of Shock-Related Myocardial Injury Sustained from a Life-Saving Therapy.

Int J Mol Sci 2021 May 8;22(9). Epub 2021 May 8.

Service de Cardiologie, Hôpital Trousseau, Université de Tours, 37044 Tours, France.

Implantable cardiac defibrillators (ICDs) are recommended to prevent the risk of sudden cardiac death. However, shocks are associated with an increased mortality with a dose response effect, and a strategy of reducing electrical therapy burden improves the prognosis of implanted patients. We review the mechanisms of defibrillation and its consequences, including cell damage, metabolic remodeling, calcium metabolism anomalies, and inflammatory and pro-fibrotic remodeling. Electrical shocks do save lives, but also promote myocardial stunning, heart failure, and pro-arrhythmic effects as seen in electrical storms. Limiting unnecessary implantations and therapies and proposing new methods of defibrillation in the future are recommended.
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http://dx.doi.org/10.3390/ijms22095003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125879PMC
May 2021

Left bundle area pacing, an elegant alternative in failed cardiac resynchronization therapy implantation: A case report.

J Electrocardiol 2021 Jul-Aug;67:31-32. Epub 2021 May 13.

Service de Cardiologie, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Université François Rabelais, Tours, France.

Left ventricular lead placement for cardiac resynchronization therapy may be challenging or even impossible. Left bundle area pacing has emerged as an interesting alternative method in case of failed implantation.
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http://dx.doi.org/10.1016/j.jelectrocard.2021.05.003DOI Listing
October 2021

Leadless cardiac pacemaker implantation in patient with active tricuspid endocarditis.

Europace 2021 May 7. Epub 2021 May 7.

Department of Cardiology, Trousseau Hospital, University of Tours, 37044 Tours, France.

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http://dx.doi.org/10.1093/europace/euab081DOI Listing
May 2021

The IC-D score for predicting prophylactic cardioverter-defibrillator implantation following acute myocardial infarction.

Pacing Clin Electrophysiol 2021 Jun 24;44(6):973-979. Epub 2021 Apr 24.

Cardiology Department, Trousseau Hospital, University of Tours, Tours, France.

Background: A reduced left ventricular ejection fraction (LVEF) ≤35% ≥6 weeks following an acute myocardial infarction (MI) may indicate prophylactic implantation of a cardioverter-defibrillator (ICD). We sought to find predictors of absence of significant left ventricular (LV) remodeling post-MI.

Methods: All consecutive patients hospitalized for acute MI with an LVEF ≤35% at discharge in our institution from 2010 were retrospectively included. Patients were assigned to two groups according to the persistence of an LVEF ≤35% (ICD+) or a recovery >35% (ICD-). Logistic regression was performed to build a predictive score, which was then externally validated.

Results: Among a total of 1533 consecutive MI patients, 150 met inclusion criteria, 53 (35%) in the ICD+ group and 97 in the ICD group. After multivariable analyses, an LVEF ≤25% at discharge (adjusted OR 6.23 [2.47 to 17.0], p < .0001) and a CPK peak at the MI acute phase >4600 UI/L (adjusted OR 9.99 [4.27 to 25.3], p < .0001) both independently predicted non-recovery at 6 weeks. The IC-D (Increased Cpk-LV Dysfunction) score predicted persistent LVEF ≤35% with areas under curve of 0.83 and 0.73, in the study population and in a multicenter validation cohort of 150 patients, respectively (p < .0001).

Conclusions: The association of a severely reduced LVEF and a major release of myocardial necrosis biomarkers at the acute phase of MI predict unfavorable remodeling, and prophylactic ICD implantation.
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http://dx.doi.org/10.1111/pace.14244DOI Listing
June 2021

Acute pathophysiological myocardial changes following intra-cardiac electrical shocks using a proteomic approach in a sheep model.

Sci Rep 2020 11 20;10(1):20252. Epub 2020 Nov 20.

Service de Cardiologie, Centre Hospitalier Universitaire Trousseau Et EA7505, Faculté de Médecine, Université François Rabelais, Tours, France.

Implantable cardioverter-defibrillators (ICD) are meant to fight life-threatening ventricular arrhythmias and reduce overall mortality. Ironically, life-saving shocks themselves have been shown to be independently associated with an increased mortality. We sought to identify myocardial changes at the protein level immediately after ICD electrical shocks using a proteomic approach. ICD were surgically implanted in 10 individuals of a healthy male sheep model: a control group (N = 5) without any shock delivery and a shock group (N = 5) with the delivery of 5 consecutive shocks at 41 J. Myocardial tissue samples were collected at the right-ventricle apex near to the lead coil and at the right ventricle basal free wall region. Global quantitative proteomics experiments on myocardial tissue samples were performed using mass spectrometry techniques. Proteome was significantly modified after electrical shock and several mechanisms were associated: protein, DNA and membrane damages due to extreme physical conditions induced by ICD-shock but also due to regulated cell death; metabolic remodeling; oxidative stress; calcium dysregulation; inflammation and fibrosis. These proteome modifications were seen in myocardium both "near" and "far" from electrical shock region. N-term acetylated troponin C was an interesting tissular biomarker, significantly decreased after electrical shock in the "far" region (AUC: 0.93). Our data support an acute shock-induced myocardial tissue injury which might be involved in acute paradoxical deleterious effects such as heart failure and ventricular arrhythmias.
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http://dx.doi.org/10.1038/s41598-020-77346-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679418PMC
November 2020

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

Genet Med 2021 01 7;23(1):47-58. Epub 2020 Sep 7.

Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.

Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.

Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.

Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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http://dx.doi.org/10.1038/s41436-020-00946-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790744PMC
January 2021

Futility Risk Model for Predicting Outcome After Transcatheter Aortic Valve Implantation.

Am J Cardiol 2020 09 7;130:100-107. Epub 2020 Jun 7.

Service de Cardiologie, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Université de Tours, France.

Risk-benefit assessment for transcatheter aortic valve implantation (TAVI) is still a matter of debate. We aimed to identify patients with a bad outcome within 1 year after TAVI, and to develop a Futile TAVI Simple score (FTS). Based on the administrative hospital-discharge database, all consecutive patients treated with percutaneous TAVI in France between 2010 and 2018 were included. A prediction model was derived and validated for 1-year all-cause death after TAVI (considered as futility) by using split-sample validation: 20,443 patients were included in the analysis (mean age 83 ± 7 years). 7,039 deaths were recorded (yearly incidence rate 15.5%), among which 3,702 (53%) occurred in first year after TAVI procedure. In the derivation cohort (n = 10,221), the final logistic regression model included male sex, history of hospital stay with heart failure, history of pulmonary oedema, atrial fibrillation, previous stroke, vascular disease, renal disease, liver disease, pulmonary disease, anaemia, history of cancer, metastasis, depression and denutrition. The area under the curve (AUC) for the FTS was 0.674 (95%CI 0.660 to 0.687) in the derivation cohort and 0.651 (95%CI 0.637 to 0.665) in the validation cohort (n = 10,222). The Hosmer-Lemeshow test had a p-value of 0.87 suggesting an accurate calibration. The FTS score outperformed EuroSCORE II, Charlson comorbidity index and frailty index for identifying futility. Based on FTS score, 7% of these patients were categorized at high risk with a 1-year mortality at 43%. In conclusion, the FTS score, established from a large nationwide cohort of patients treated with TAVI, may provide a relevant tool for optimizing healthcare decision.
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http://dx.doi.org/10.1016/j.amjcard.2020.05.043DOI Listing
September 2020

Mortality and cardiac resynchronization therapy with or without defibrillation in primary prevention.

Europace 2020 08;22(8):1224-1233

Service de Cardiologie, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Université de Tours, EA7505 Tours, France.

Aims: Cardiac resynchronization therapy with (CRTD) or without (CRTP) defibrillator is recommended in selected patient with systolic chronic heart failure and wide QRS. There is no guideline firmly indicating choice between CRTP and CRTD in primary prevention, particularly in older patients.

Methods And Results: Based on the French administrative hospital-discharge database, information was collected from 2010 to 2017 for all patients implanted with CRTP or CRTD in primary prevention. Outcome analyses were undertaken in the total study population and in propensity-matched samples. During follow-up (913 days, SD 841, median 701, IQR 151-1493), 45 697 patients were analysed (CRTP 19 266 and CRTD 26 431). Incidence rate (%patient/year) of all-cause mortality was higher in CRTP patients (11.6%) than in CRTD patients (6.8%) [hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.63-1.76, P < 0.001]. After propensity-matched analyses, mortality of patients over 75 years old with non-ischaemic cardiomyopathy (NICM) was not different with CRTP and CRTD (HR 0.93, 95% CI 0.80-1.09, P = 0.39). The CRTP patients under 75 years old with NICM had a higher mortality than CRTD patients (HR 1.22, 95% CI 1.03-1.45, P = 0.02). Mortality rate was also higher with CRTP than with CRTD irrespectively of age in patients with ischaemic cardiomyopathy (ICM) (<75 years old: HR 1.22, 95% CI 1.08-1.37, P = 0.01; ≥75 years old: HR 1.13, 95% CI 1.04-1.22, P = 0.003).

Conclusion: In this real-life study, CRTD was associated with a significantly lower all-cause mortality than CRTP in patients with ICM and in patients with NICM under 75 years old. Patients over 75 years old with NICM did not have lower mortality with primary prevention CRTD implantation.
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http://dx.doi.org/10.1093/europace/euaa096DOI Listing
August 2020

Hypercontractile esophagus resolved after radiofrequency catheter ablation for atrial fibrillation: About a case.

Neurogastroenterol Motil 2020 11 1;32(11):e13886. Epub 2020 Jun 1.

Department of Gastroenterology, Hôpital Trousseau, CHRU de Tours, Tours, France.

The pathophysiology of jackhammer esophagus is complex and remains unclear. Radiofrequency catheter ablation is indicated for highly symptomatic and drug-refractory atrial fibrillation. This technique can induce esophageal and nerve lesions, due to thermal injury. In this report, we describe a case of hypercontractile esophagus diagnosed by HRM (high-resolution manometry). Esophageal symptoms and HRM normalized immediately after RFCA, and we discuss the pathophysiology of hypercontractile esophagus.
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http://dx.doi.org/10.1111/nmo.13886DOI Listing
November 2020

Ischemic Stroke in Patients With Sinus Node Disease, Atrial Fibrillation, and Other Cardiac Conditions.

Stroke 2020 06 11;51(6):1674-1681. Epub 2020 May 11.

From the Service de Cardiologie, Centre Hospitalier Universitaire Trousseau, Faculté de Médecine (A.B., A.B., J.H., N.C., D.B., L.F.), Université François Rabelais, Tours, France.

Background and Purpose- Atrial fibrillation (AF) is known to increase risk of ischemic stroke (IS), but the risk of IS in isolated sinus node disease (SND) is unclear. We compared the incidence of IS in patients with SND, patients with AF, and in a control population with other cardiac diseases (disease of the circulatory system using the ). Methods- This French longitudinal cohort study was based on the national database covering hospital care for the entire population from 2008 to 2015. Results- Of 1 692 157 patients included in the cohort, 100 366 had isolated SND, 1 564 270 had isolated AF, and 27 521 had AF associated with SND. Incidence of IS during follow-up was higher in isolated patients with AF than in AF associated with SND (yearly rate 2.22% versus 2.06%) and in isolated patients with AF than in isolated patients with SND (yearly rate 2.22% versus 1.59%). The incidence of IS was lower in a control population with other cardiac conditions (n=479 108) compared with SND and patients with AF (0.96%/y, 1.59%/y, and 2.22%/y, respectively). After 1:1 propensity score matching, SND was associated with lower incidence of IS compared to AF (hazard ratio, 0.77 [95% CI, 0.73-0.82]) but higher incidence of IS compared to control population (hazard ratio, 1.27 [95%CI, 1.19-1.35]). Conclusions- Patients with SND had a lower risk of thromboembolic events than patients with AF but a higher risk than a control population with other cardiac diseases. Randomized clinical trial in a selected SND population, with, for example, a high CHADS-VASc score, would be required to determine the value of IS prevention by anticoagulation.
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http://dx.doi.org/10.1161/STROKEAHA.120.029048DOI Listing
June 2020

Pacemaker Implantation After Balloon- or Self-Expandable Transcatheter Aortic Valve Replacement in Patients With Aortic Stenosis.

J Am Heart Assoc 2020 05 2;9(9):e015896. Epub 2020 May 2.

Service de Cardiologie Centre Hospitalier Universitaire Trousseau et Faculté de Médecine EA7505 Université de Tours France.

Background The incidence of conduction abnormalities requiring permanent pacemaker implantation (PPI) after transcatheter aortic valve replacement (TAVR) with early and later generation prostheses remains debated. Methods and Results Based on the administrative hospital-discharge database, we collected information for all patients treated with TAVR between 2010 and 2019 in France. We compared the incidence of PPI after TAVR according to the type and generation of valve implanted. A total of 49 201 patients with aortic stenosis treated with TAVR using the balloon-expandable (BE) Edwards SAPIEN valve (early Sapien XT and latest Sapien 3) or the self-expanding (SE) Medtronic CoreValve (early CoreValve and latest Evolut R) were found in the database. Mean (SD) follow-up was 1.2 (1.5 years) (median [interquartile range] 0.6 [0.1-2.0] years). PPI after the procedure was reported in 13 289 patients, among whom 11 010 (22.4%) had implantation during the first 30 days. In multivariable analysis, using early BE TAVR as reference, adjusted odds ratio (95% CI) for PPI during the first 30 days was 0.88 (0.81-0.95) for latest BE TAVR, 1.40 (1.27-1.55) for early SE TAVR, and 1.17 (1.07-1.27) for latest SE TAVR. Compared with early BE TAVR, the adjusted hazard ratio for PPI during the whole follow-up was 1.01 (0.95-1.08) for latest BE TAVR, 1.30 (1.21-1.40) for early SE TAVR, and 1.25 (1.18-1.34) for latest SE TAVR. Conclusions In patients with aortic stenosis treated with TAVR, our systematic analysis at a nationwide level found higher rates of PPI than previously reported. BE technology was independently associated with lower incidence rates of PPI both at the acute and chronic phases than SE technology. Recent generations of TAVR were not independently associated with different rates of PPI than early generations during the overall follow-up.
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http://dx.doi.org/10.1161/JAHA.120.015896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428568PMC
May 2020

Incident Comorbidities, Aging and the Risk of Stroke in 608,108 Patients with Atrial Fibrillation: A Nationwide Analysis.

J Clin Med 2020 Apr 24;9(4). Epub 2020 Apr 24.

Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool L7 8TX, UK.

Background: We hypothesized that the change in stroke risk profile between baseline and follow-up may be a better predictor of ischemic stroke than the baseline stroke risk determination using the CHADS-VASc score ((congestive heart failure, hypertension, age ≥75 years (doubled), diabetes, stroke/transient ischemic attack/thromboembolism (doubled), vascular disease (prior myocardial infarction, peripheral artery disease, or aortic plaque), age 65-75 years, sex category (female))).

Methods: We collected information for all patients treated with atrial fibrillation (AF) in French hospitals between 2010 and 2019. We studied 608,108 patients with AF who did not have risk factors of the CHADS-VASc score (except for age and sex). The predictive accuracies of baseline and follow-up CHADS-VASc scores, as well as the 'Delta CHADS-VASc' (i.e., change/difference between the baseline and follow-up CHADS-VASc scores) for prediction of ischemic stroke were studied.

Results: The mean CHADS-VASc score at baseline was 1.7, and increased to 2.4 during follow-up of 2.2 ± 2.4 years, (median (interquartile range: IQR) 1.2 (0.1-3.8) years), resulting in a mean Delta CHADS-VASc score of 0.7. Among 20,082 patients suffering ischemic stroke during follow-up, 67.1% had a Delta CHADS-VASc score ≥1 while they were only 40.4% in patients without ischemic stroke. The follow-up CHADS-VASc score and Delta CHADS-VASc score were predictors of ischemic stroke (C-index 0.670, 95% confidence interval (CI) 0.666-0.673 and 0.637, 95%CI 0.633-0.640) and they performed better than baseline CHADS-VASc score (C-index 0.612, 95%CI 0.608-0.615, < 0.0001).

Conclusions: Stroke risk was non-static, and many AF patients had ≥1 new stroke risk factor(s) before ischemic stroke occurred. The follow-up CHADS-VASc score and its change (i.e., 'Delta CHADS-VASc') were better predictors of ischemic stroke than relying on the baseline CHADS-VASc score.
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http://dx.doi.org/10.3390/jcm9041234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230460PMC
April 2020

Prognosis of Type 2 Myocardial Infarction Patients Implanted With a Prophylactic Defibrillator (from the Very-High-Rate Registry).

Am J Cardiol 2020 04 7;125(7):1001-1005. Epub 2020 Jan 7.

Cardiology Department, Trousseau Hospital, University of Tours, Tours, France. Electronic address:

An implantable cardioverter defibrillator (ICD) is recommended in primary prevention patients with a coronary artery disease (CAD) and reduced left ventricular ejection fraction. Benefits of ICD in CAD unrelated to coronary thrombosis are unknown. We sought to compare the prognosis of patients with CAD implanted with a prophylactic ICD according to the type of myocardial infarction (MI). Patients from the Very-High-Rate registry implanted with a prophylactic ICD for CAD between 2006 and 2016 were retrospectively included. Cardiac resynchronization therapy patients were excluded. Patients with type 2 MI were matched (1:4) with patients with type 1 MI using propensity score. The following events were collected: death, hospitalization for heart failure, cardiac transplantation, and appropriated therapies on ventricular arrhythmia (≥220 beats/min). Among 571 consecutive ischemic patients, 65 type 2 MI patients were matched to 260 type 1. After a mean follow up of 55 ± 36 months, 63 patients (24%) died in type 1 group, 18 (28%) in type 2 group (p = 0.19). Survival rate from appropriate therapies on high-rate ventricular arrhythmias was significantly lower in type 2 group (p = 0.04). In conclusion, patients implanted with a prophylactic ICD for severe CAD, whether type 1 or type 2 MI, have similar outcomes.
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http://dx.doi.org/10.1016/j.amjcard.2019.12.053DOI Listing
April 2020

Number of electrocardiogram leads in the diagnosis of spontaneous Brugada syndrome.

Arch Cardiovasc Dis 2020 Mar 29;113(3):152-158. Epub 2019 Nov 29.

L'Institut du thorax, Inserm, CNRS, université de Nantes, CHU de Nantes, 44093 Nantes, France. Electronic address:

Background: The recently recommended single lead-based criterion for the diagnosis of Brugada syndrome may lead to overdiagnosis of this disorder and overestimation of the risk of sudden cardiac death.

Aim: To investigate the value of a single-lead diagnosis in patients with Brugada syndrome and a spontaneous type 1 electrocardiogram.

Methods: Consecutive patients with Brugada syndrome were included in a multicentre prospective registry; only those with a spontaneous type 1 electrocardiogram were enrolled. Clinical and electrocardiogram data were reviewed by two physicians blinded to the patients' clinical and genetic status.

Results: Among 1613 patients, 505 (31%) were enrolled (79% male; mean age 46±15 years). A spontaneous type 1 electrocardiogram pattern was found in one lead in 250 patients (group 1), in two leads in 227 patients (group 2) and in three leads in 27 patients (group 3). Groups were similar except for individuals in group 3, who presented more frequently a fragmented QRS complex, an early repolarization pattern and a prolonged T-T interval. After a mean follow-up of 6.4±4.7 years, ventricular arrhythmia, sudden cardiac death or implantable cardiac defibrillator shock occurred in 46 (9%) patients, without differences between groups.

Conclusion: The prognosis of Brugada syndrome with a spontaneous type 1 electrocardiogram pattern does not appear to be affected by the number of leads required for the diagnosis.
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http://dx.doi.org/10.1016/j.acvd.2019.10.007DOI Listing
March 2020

Early mortality after implantable cardioverter defibrillator: Incidence and associated factors.

Int J Cardiol 2020 02 30;301:114-118. Epub 2019 Oct 30.

AP-HP, CHU Bichat Claude Bernard and Université Paris Diderot, 75018, Paris, France. Electronic address:

Background: According to guidelines, implantable cardioverter defibrillator (ICD) candidates must have a "reasonable expectation of survival with a good functional status >1 year". Identifying risk for early mortality in ICD candidates could be challenging. We aimed to identify factors associated with a ≤1-year survival among patients implanted with ICDs.

Methods: The DAI-PP program was a multicenter, observational French study that included all patients who received a primary prevention ICD in the 2002-2012 period. Characteristics of patients who survived ≤1 year following the implantation were compared with those who survived >1 year, and predictors of early death determined.

Results: Out of the 5539 enrolled patients, survival status at 1 year was known for a total of 5,457, and overall 230 (4.2%) survived ≤1 year. Causes of death were similar in the two groups. Patients with ≤1-year survival had lower rates of appropriate (14 vs. 23%; P = 0.004) and inappropriate ICD therapies (2 vs. 7%; P = 0.009) than patients who lived >1 year after ICD implantation. In multivariate analysis, older age, higher NYHA class (≥III), and atrial fibrillation were significantly associated with ≤1-year survival. Presence of all 3 risk factors was associated with a cumulative 22.63% risk of death within 1 year after implantation.

Conclusions: This is the largest study determining the factors predicting early mortality after ICD implantation. Patients dying within the first year had low ICD therapy rates. A combination of clinical factors could potentially identify patients at risk for early mortality to help improve selection of ICD candidates.
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http://dx.doi.org/10.1016/j.ijcard.2019.09.033DOI Listing
February 2020

How to upgrade a leadless pacemaker to cardiac resynchronization therapy.

J Cardiovasc Electrophysiol 2019 11 25;30(11):2578-2581. Epub 2019 Sep 25.

Cardiology Department, Trousseau Hospital, University of Tours, Tours, France.

Introduction: We sought to develop an efficient method to upgrade pacing-induced cardiomyopathy (PICM) patients from a leadless pacemaker (LPM) to cardiac resynchronization therapy.

Methods And Results: Three consecutive patients with chronic atrial fibrillation, implanted with an LPM, with permanent right ventricular pacing, and who developed left ventricular systolic dysfunction due to PICM, were included. A conventional biventricular pacemaker with two different coronary sinus leads, one used for left lateral ventricular pacing, one for early right ventricular sensing, was implanted. It was then synchronized with the LPM working as the right ventricular pacing lead to provide biventricular pacing. The upgrading technique was feasible in all cases, without any perioperative complication. All patients had an improved clinical status during follow-up.

Conclusion: This new upgrading technique allows efficient cardiac resynchronization therapy in LPM patients while preventing tricuspid valve crossing and providing an increased battery longevity.
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http://dx.doi.org/10.1111/jce.14169DOI Listing
November 2019

Implantable cardioverter defibrillator therapy for primary prevention of sudden cardiac death in the real world: Main findings from the French multicentre DAI-PP programme (pilot phase).

Arch Cardiovasc Dis 2019 Aug - Sep;112(8-9):523-531. Epub 2019 Aug 27.

Clinique Pasteur, 31076 Toulouse, France; CHU de Poitiers, 86021 Poitiers, France; Université de Poitiers, 86073 Poitiers, France; CHU de Grenoble, 38700 La Tronche, France; Centre cardiologique du Nord, 93200 Saint-Denis, France; Paris Cardiovascular Research Centre (Inserm U970), 75015 Paris, France; Maxcure Hospitals, 500081 Hyderabad, Telangana, India; Royal Papworth Hospital NHS Foundation Trust, Cambridge University Health Partners, CB2 0AY Cambridge, UK; Hospital da Luz Arrabida, 4400-346 Vila Nova de Gaia, Portugal; Hopital privé du Confluent, 44000 Nantes, France; Barts Heart Centre, Barts Health NHS Trust, EC1A 7BE London, UK; Hôpital Bichat-Claude-Bernard, 75018 Paris, France; IRSN, 92260 Fontenay aux Roses, France; CHU Haut Lévêque, 33600 Pessac, France; CHU Trousseau, 37170 Chambray-lès-Tours, France; CHRU de Lille, 59000 Lille, France; CHU Pontchaillou, 35033 Rennes, France; CHU Brabois, 54500 Vandœuvre-lès-Nancy, France; Hôpital de La Timone, 13005 Marseille, France; Unité de Rythmologie, Hôpital européen Georges Pompidou, 20-40, rue Leblanc, 75908 Paris cedex 15, France; Paris Descartes University, 75006 Paris, France.

This review summarizes the main findings of the French multicentre DAI-PP pilot programme, and discusses the related clinical and research perspectives. This project included retrospectively (2002-2012 period) more than 5000 subjects with structural heart disease who received an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death, and were followed for a mean period of 3 years. The pilot phase of the DAI-PP programme has provided valuable information on several practical and clinically relevant aspects of primary prevention ICD implantation in the real-world population, which are summarized in this review. This pilot has led to a prospective evaluation that started in May 2018, assessing ICD therapy in primary and secondary prevention in patients with structural and electrical heart diseases, with remote monitoring follow-up using a dedicated platform. This should further enhance our understanding of sudden cardiac death, to eventually optimize the field of preventative actions.
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http://dx.doi.org/10.1016/j.acvd.2019.05.005DOI Listing
November 2019

Stimulation of P2Y11 receptor protects human cardiomyocytes against Hypoxia/Reoxygenation injury and involves PKCε signaling pathway.

Sci Rep 2019 08 12;9(1):11613. Epub 2019 Aug 12.

EA4245 Transplantation, Immunologie et Inflammation, Loire Valley Cardiovascular Collaboration & Université de Tours, Tours, France.

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 HO-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.
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http://dx.doi.org/10.1038/s41598-019-48006-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6690895PMC
August 2019

Multisite pacing via a quadripolar lead for cardiac resynchronization therapy.

J Interv Card Electrophysiol 2019 Oct 18;56(1):117-125. Epub 2019 Jul 18.

Service de Cardiologie, Centre Hospitalier Universitaire Trousseau et EA7505, Faculté de Médecine, Université François Rabelais, Tours, France.

Cardiac resynchronization therapy is challenging. Up to 40% of patients are non-responder. Multisite pacing via a quadripolar lead, also called multipoint/multipole pacing (MPP), is a debated alternative. In this review, we summarize evidence in the literature, tips and pitfalls related to MPP programming, and the different algorithms of MPP in different manufacturers.
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http://dx.doi.org/10.1007/s10840-019-00592-1DOI Listing
October 2019

Development and Validation of a New Risk Prediction Score for Life-Threatening Ventricular Tachyarrhythmias in Laminopathies.

Circulation 2019 07 3;140(4):293-302. Epub 2019 Jun 3.

APHM, Centre de référence des maladies neuromusculaires PACA-Réunion-Rhône Alpes, Hôpital Timone; Aix Marseille Université, Inserm UMR_S 910, GMGF, France (E.S.).

Background: An accurate estimation of the risk of life-threatening (LT) ventricular tachyarrhythmia (VTA) in patients with LMNA mutations is crucial to select candidates for implantable cardioverter-defibrillator implantation.

Methods: We included 839 adult patients with LMNA mutations, including 660 from a French nationwide registry in the development sample, and 179 from other countries, referred to 5 tertiary centers for cardiomyopathies, in the validation sample. LTVTA was defined as (1) sudden cardiac death or (2) implantable cardioverter defibrillator-treated or hemodynamically unstable VTA. The prognostic model was derived using the Fine-Gray regression model. The net reclassification was compared with current clinical practice guidelines. The results are presented as means (SD) or medians [interquartile range].

Results: We included 444 patients, 40.6 (14.1) years of age, in the derivation sample and 145 patients, 38.2 (15.0) years, in the validation sample, of whom 86 (19.3%) and 34 (23.4%) experienced LTVTA over 3.6 [1.0-7.2] and 5.1 [2.0-9.3] years of follow-up, respectively. Predictors of LTVTA in the derivation sample were: male sex, nonmissense LMNA mutation, first degree and higher atrioventricular block, nonsustained ventricular tachycardia, and left ventricular ejection fraction (https://lmna-risk-vta.fr). In the derivation sample, C-index (95% CI) of the model was 0.776 (0.711-0.842), and the calibration slope 0.827. In the external validation sample, the C-index was 0.800 (0.642-0.959), and the calibration slope was 1.082 (95% CI, 0.643-1.522). A 5-year estimated risk threshold ≥7% predicted 96.2% of LTVTA and net reclassified 28.8% of patients with LTVTA in comparison with the guidelines-based approach.

Conclusions: In comparison with the current standard of care, this risk prediction model for LTVTA in laminopathies significantly facilitated the choice of candidates for implantable cardioverter defibrillators.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03058185.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.039410DOI Listing
July 2019

End-of-service management of leadless cardiac pacemakers: a case report.

Europace 2019 Aug;21(8):1245

Department of Cardiology, Trousseau Hospital, University of Tours, Tours, France.

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http://dx.doi.org/10.1093/europace/euz054DOI Listing
August 2019

Prophylactic implantable cardioverter-defibrillator in the very elderly.

Europace 2019 Jul;21(7):1063-1069

Paris Cardiovascular Research Center, Paris, France.

Aims: Current guidelines do not propose any age cut-off for the primary prevention implantable cardioverter-defibrillator (ICD). However, the risk/benefit balance in the very elderly population has not been well studied.

Methods And Results: In a multicentre French study assessing patients implanted with an ICD for primary prevention, outcomes among patients aged ≥80 years were compared with <80 years old controls matched for sex and underlying heart disease (ischaemic and dilated cardiomyopathy). A total of 300 ICD recipients were enrolled in this specific analysis, including 150 patients ≥80 years (mean age 81.9 ± 2.0 years; 86.7% males) and 150 controls (mean age 61.8 ± 10.8 years). Among older patients, 92 (75.6%) had no more than one associated comorbidity. Most subjects in the elderly group got an ICD as part of a cardiac resynchronization therapy procedure (74% vs. 46%, P < 0.0001). After a mean follow-up of 3.0 ± 2 years, 53 patients (35%) in the elderly group died, including 38.2% from non cardiovascular causes of death. Similar proportion of patients received ≥1 appropriate therapy (19.4% vs. 21.6%; P = 0.65) in the elderly group and controls, respectively. There was a trend towards more early perioperative events (P = 0.10) in the elderly, with no significant increase in late complications (P = 0.73).

Conclusion: Primary prevention ICD recipients ≥80 years in the real world had relatively low associated comorbidity. Rates of appropriate therapies and device-related complications were similar, compared with younger subjects. Nevertheless, the inherent limitations in interpreting observational data on this particular competing risk situation call for randomized controlled trials to provide definitive answers. Meanwhile, a careful multidisciplinary evaluation is needed to guide patient selection for ICD implantation in the elderly population.
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http://dx.doi.org/10.1093/europace/euz041DOI Listing
July 2019

Stroke and Thromboembolism in Patients With Atrial Fibrillation and Mitral Regurgitation.

Circ Arrhythm Electrophysiol 2019 03;12(3):e006990

Department of Cardiology, Centre Hospitalier Universitaire Trousseau et Faculté de Médecine, Tours, France (A. Bisson, A. Bernard, A. Bodin, N.C., D.B., L.F.).

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http://dx.doi.org/10.1161/CIRCEP.118.006990DOI Listing
March 2019

Role of medical reaction in management of inappropriate ventricular arrhythmia diagnosis: the inappropriate Therapy and HOme monitoRiNg (THORN) registry.

Europace 2019 Apr;21(4):607-615

Department of Cardiology, Centre Hospitalier Universitaire La Timone, Marseille, France.

Aims: Implantable cardioverter-defibrillators (ICDs) reduce sudden cardiac death in selected patients but inappropriate ICD shocks have been associated with increased mortality. The THORN registry aims to describe the rate of inappropriate ventricular arrhythmia diagnoses and therapies in patients followed by remote monitoring, as well as the following delay to next patient contact (DNPC).

Methods And Results: One thousand eight hundred and eighty-two patients issued from a large remote monitoring database first implanted with an ICD for primary or secondary prevention in 110 French hospitals from 2007 to 2014 constitute the THORN population. Among them, 504 patients were additionally followed prospectively for evaluation of the DNPC. Eight hundred and ninety-five out of 1551 (58%) patients had ischaemic heart disease and 358/771 (46%) were implanted for secondary prevention. During 13.7 ± 3.4 months of follow-up, the prevalence of first inappropriate diagnosis in a ventricular arrhythmia zone with enabled therapy was 162/1882 (9%). Among those patients, 122/162 (75%) suffered at least one inappropriate therapy and 58/162 (36%) at least one inappropriate shock. Eighty-three out of 162 (51%) of first inappropriate diagnosis occurred during the first 4 months following implantation. The median DNPC was 8 days (interquartile range 1-26). At least one other day with recording of an inappropriate diagnosis of the same cause occurred in 13/43 (30%) of available DNPC periods, with an inappropriate therapy in 7/13 (54%).

Conclusion: Inappropriate diagnoses occurred in 9% of patients implanted with an ICD during the first 14 months. The DNPC after inadequate ventricular arrhythmia diagnoses remains long in daily practice and should be optimized.

Clinicaltrials.gov Identifier: NCT01594112.
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http://dx.doi.org/10.1093/europace/euy284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6452297PMC
April 2019

Distal-to-proximal delay for ablation of premature ventricular contractions.

J Cardiovasc Electrophysiol 2019 02 27;30(2):205-211. Epub 2018 Dec 27.

Cardiology Department, University of Tours, Tours, France.

Introduction: Ablation of premature ventricular contractions (PVCs) has emerged as a safe and effective treatment in patients experiencing a high PVCs burden. Mapping of PVCs origin may sometimes be challenging. We sought to evaluate the accuracy of a new electrophysiological criterion, the distal-to-proximal (DP) delay, at localizing the optimal site for ablation of ventricular ectopic foci.

Methods And Results: Consecutive patients with ablation attempts of symptomatic PVCs were included. Prematurity and DP delay-that is, the time duration between the onset of ablation catheter distal bipolar electrogram and the onset of proximal bipolar electrogram-were measured at successful and unsuccessful ablation sites by three blinded experienced electrophysiologists. Mean DP delay at effective ablation sites (N = 30) was significantly higher than at ineffective sites ( N = 55) (23 ± 9 vs 11 ± 8 milliseconds; P < 0.0001). DP delay had good-to-excellent interrater reliability. A DP delay greater than or equal to 15 milliseconds had the highest accuracy at predicting a successful ablation site (sensitivity 0.97, the area under receiver operating characteristic curve 0.87; P < 0.0001).

Conclusion: DP delay is an additional, simple, and effective electrophysiological parameter to accurately localize PVCs foci.
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http://dx.doi.org/10.1111/jce.13807DOI Listing
February 2019

Galectin-3 predicts response and outcomes after cardiac resynchronization therapy.

J Transl Med 2018 11 3;16(1):299. Epub 2018 Nov 3.

Cardiology Department, Trousseau Hospital, University of Tours, 37044, Tours, France.

Background: Cardiac resynchronization therapy (CRT) reduces symptoms, morbidity and mortality in chronic heart failure patients with wide QRS complexes. However, approximately one third of CRT patients are non-responders. Myocardial fibrosis is known to be associated with absence of response. We sought to see whether galectin-3, a promising biomarker involved in fibrosis processes, could predict response and outcomes after CRT.

Methods: Consecutive patients eligible for implantation of a CRT device with a typical left bundle branch block ≥ 120 ms were prospectively included. Serum Gal-3 level, Selvester ECG scoring, and cardiac magnetic resonance with analysis of late gadolinium enhancement (LGE) were ascertained. Response to CRT was defined by a composite endpoint at 6 months: no death, nor hospitalization for major cardiovascular event, and a significant decrease in left ventricular end-systolic volume of 15% or more.

Results: Sixty-one patients were included (age 61 ± 5 years, ejection fraction 27 ± 5%), 59% with non-ischemic cardiomyopathy. At 6 months, 49 patients (80%) were considered responders. Responders had a lower percentage of LGE (8 ± 13% vs 22 ± 16%, p = 0.006), and a trend towards lower rates of galectin-3 (16 ± 6 ng/mL vs 19 ± 8 ng/mL, p = 0.13). LGE ≥ 14% and Gal-3 ≥ 22 ng/mL independently predicted response to CRT (OR = 0.17 [0.03-0.62], p = 0.007, and OR = 0.11 [0.02-0.04], p < 0.001, respectively). At 48 months of follow-up, 12 patients had been hospitalized for a major cardiovascular event or had died. Galectin-3 level predicted long-term outcomes (HR = 3.31 [1.00-11.34], p = 0.05).

Conclusions: Gal-3 serum level predicts the response to CRT at 6 months and long-term outcomes in chronic heart failure patients.
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http://dx.doi.org/10.1186/s12967-018-1675-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6215623PMC
November 2018
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