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  • Bonnet, G  (6)
  • 1
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    Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation and association with mortality: a population-based study
    Oxford University Press (OUP) ; 2020
    In:  European Heart Journal Vol. 41, No. Supplement_2 ( 2020-11-01)
    Details
    In: European Heart Journal, Oxford University Press (OUP), Vol. 41, No. Supplement_2 ( 2020-11-01)
    Abstract: Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. However, the associations between CAV trajectories and mortality remains poorly described. Purpose We aimed to identify the different evolutive profiles of CAV and to determine the respective association with all-cause mortality. Methods Heart transplant recipients receiving care at 4 academic centers were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The mainoutcome was a prediction for CAV trajectories using unsupervised latent class mixed models. We then identified their association with all-cause mortality (NCT04117152). Results Overall, 1,301 patients were included (815 and 486 in the development and validation cohorts, respectively). The median follow-up post-transplant was 6.6 years (IQR=4.7) with 4,710 coronary angiographies analyzed (3.6±1.6 CAV assessments per patient). We identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i)Patients without CAV at baseline and non-progression (n=823, 63.3%), ii) patients without CAV at baseline and late onset CAV progression (n=79, 6.1%), iii) patients with mild baseline CAV and mild progression (n=261, 20.1), iv) patients with mild baseline CAV and accelerated CAV progression (n=138, 10.6%, discrimination 0.95). The 4 CAV trajectories showed gradient for all-cause mortality (p & lt;0.001). Trajectories #3 and #4 were associated with higher mortality rates (10-year patient survival of 73.43% [95% CI 65.18–80.02] and 51.89% [95% CI 38.76–63.51] , respectively) as compared with trajectories #1, and #2 that were characterized by 10-year patient survival of 80.01 [95% CI 76.38–84.82] and 83.49% [95% CI 71.34–90.80], respectively (p & lt;0.001). Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 robust CAV trajectories. These different profiles were associated with distinct prognosis. Our results provide the basis for a trajectory-based assessment of heart transplant patients for early patient risk stratification and patient monitoring. Figure 1. Overall 10-year survival probability according to the CAV trajectory in the overall cohort (n=1,301). The left part represents the main profiles CAV grades identified with latent class mixed models. Thick lines represent latent class trajectory; thin lines represent CAV individual patient trajectory. The right part represent the Kaplan Meier curves of the different trajectories. Funding Acknowledgement Type of funding source: None
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    URL: Article
    DOI: 10.1093/ehjci/ehaa946.1105
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 2
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    Feasibility and prognostic value of vasodilator stress perfusion CMR in patients with atrial fibrillation
    Oxford University Press (OUP) ; 2020
    In:  European Heart Journal Vol. 41, No. Supplement_2 ( 2020-11-01)
    Details
    In: European Heart Journal, Oxford University Press (OUP), Vol. 41, No. Supplement_2 ( 2020-11-01)
    Abstract: Several studies have demonstrated the consistently high diagnostic and prognostic value of stress perfusion imaging with cardiovascular magnetic resonance (CMR). The feasibility and the prognostic value of vasodilator stress perfusion CMR in patients with atrial fibrillation (AF) is unknown, because most studies have excluded arrhythmic patients from analysis. Purpose The aim of our study was to assess the technical feasibility and the prognostic value of vasodilator stress perfusion CMR in patients with AF. Material Between 2008 and 2018, we prospectively included consecutive patients with AF referred for vasodilator stress perfusion CMR with dipyridamole. They were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or non-fatal myocardial infarction (MI). The secondary outcome was all-cause mortality. The diagnosis of AF was confirmed on 12-lead ECG before and after CMR, and patients with sinus rhythm during CMR were excluded. In the CMR protocol, to limit AF-related artifacts on cine images, an arrhythmia rejection algorithm, or real-time sequences were used. Univariable and multivariable Cox regressions for MACE were performed to determine the prognostic value of inducible ischemia or late gadolinium enhancement (LGE) by CMR. Results Of 639 patients with AF and suspected or stable chronic CAD (72±9 years, 77% men), 602 (94%) completed the CMR protocol, and among those 538 (89%) completed the follow-up (median follow-up 5.1 (3.3–7.1) years). Reasons for failure to complete CMR included AF-related ECG-gating problems (n=17), intolerance to stress agent (n=7), renal failure (n=6), declining participation (n=4) and claustrophobia (n=3). Stress CMR was well tolerated without occurrence of death or severe disabling adverse event. Patients without inducible ischemia or LGE experienced a substantially lower annual event rate of MACE (1.2%) than those with ischemia and without LGE (8.9%), or those with both ischemia and LGE (9.8%; p & lt;0.001 for all). Using Kaplan-Meier analysis, the presence of myocardial ischemia identified the occurrence of MACE (hazard ratio HR 7.56; 95% confidence interval CI: 4.86–11.80; p & lt;0.001) (Figure). In a multivariable stepwise Cox regression including clinical characteristics and CMR indexes, the presence of inducible ischemia was an independent predictor of a higher incidence of MACE (HR 5.88; 95% CI: 3.70–10.07; p & lt;0.001) and all-cause mortality (HR 2.51; 95% CI: 1.47–4.17; p & lt;0.001). Conclusion Stress CMR is technically feasible and has a good discriminative prognostic value to predict the occurrence of MACE and all-cause mortality in patients with AF. Kaplan-Meier curves for MACE Funding Acknowledgement Type of funding source: None
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    URL: Article
    DOI: 10.1093/ehjci/ehaa946.0251
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 3
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    Incidence of sudden cardiac death after heart transplantation
    Oxford University Press (OUP) ; 2020
    In:  European Heart Journal Vol. 41, No. Supplement_2 ( 2020-11-01)
    Details
    In: European Heart Journal, Oxford University Press (OUP), Vol. 41, No. Supplement_2 ( 2020-11-01)
    Abstract: Sudden cardiac death (SCD) is a major contributor to the rate of mortality after heart transplantation. However, little is known about the incidence of SCD in heart recipients. Objective To assess the incidence of SCD after heart transplantation. Methods We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centers. We defined 7 main groups of causes of deaths: SCD, cardiovascular (including Cardiac allograft vasculopathy), infection, primary graft dysfunction, graft failure (including late graft dysfunction, rejection), malignancy and others. Causes of deaths were independently adjudicated by two senior cardiologists based on the analysis of death certificates and medical records. Discrepancies were resolved by discussion until a consensus was made. SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms. Results A total of 1,363 patients were included. The median follow-up post-transplant was 3.99 years (IQR=0.49–7.49). 450 patients (33%) deceased during the first year. The leading cumulative causes of death in the first year after transplantation were infection, primary graft failure, multiple organ failure during the period in intensiv car unit. Beyond the post-operativ high-risk period of the first year, the leading cumulative cause of death was SCD: among the 213 deaths that occurred beyond the first year, 44 patients (21%) died from SCD. In this period, the incidence rate of SCD reached 0,82 per 100 person-year (95% CI: 0.51–2.05). Conclusion In a large multicentric and highly phenotyped cohort of heart transplant recipients, the leading cumulative cause of death beyond the first-year post transplant was sudden cardiac death. Our results open discussion on management of heart recipient, such as the implementation of cardioverter-defibrillators. Figure 1. Cumulative incidence of causes of death in heart transplant recipients beyond the first year (n=913). Funding Acknowledgement Type of funding source: None
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    URL: Article
    DOI: 10.1093/ehjci/ehaa946.0726
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2001908-7
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  • 4
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    Determinants of sudden cardiac death after heart transplantation
    Oxford University Press (OUP) ; 2020
    In:  European Heart Journal Vol. 41, No. Supplement_2 ( 2020-11-01)
    Details
    In: European Heart Journal, Oxford University Press (OUP), Vol. 41, No. Supplement_2 ( 2020-11-01)
    Abstract: Heart transplant recipients are at high-risk of sudden cardiac death (SCD). However, risk factors of SCD in heart recipients remained poorly described. Objective To assess the predictors of SCD beyond the first-year post-transplant. Methods We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centers. We excluded patients deceased during the first year. Patients underwent an evaluation at the day of transplantation and during the first year, comprising clinical, biological, histological, immunological (circulating anti-HLA DSA) and interventional (cardiac allograft vasculopathy assessment) parameters. Echocardiographies were routinely performed in all included patients according to a prespecified protocol. According to the last consensus, SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms. Cox model analysis was used to determine the parameters associated with sudden death risk. Results A total of 913 patients were included. The median follow-up post-HT was 5.9 years (IQR=2.9–8.5). Among the 213 deaths after one year, 44 patients (21%) died from SCD. In this population, the incidence rate of SCD was 0,82 per 100 person-year (95% CI: 0,51–2,05). Among the 60 parameters tested in univariate analysis, we identified 2 independent factors of sudden death after 1 year post-HT: left ventricular ejection fraction (LVEF) ≤55% any time after transplantation ( HR 4.07, 95% CI 1.94–8.53, p & lt;0.001) and the presence of circulating anti-HLA DSA at the time of transplantation (HR 2.79, 95% CI 1.37–5.68, p=0.005). The incidence rate of SCD was 2.17 per 100 person-year (95% CI: 1.42; 4.60) and 1.21 per 100 person-year (95% CI: 0.80; 2.58) in patients with FEVG & lt;55% (n=73) and in patients with pre-formed DSA (n=260), respectively. Conclusion In a large multicentric and highly phenotyped cohort of heart transplant recipients, we identified two independent factors associated with SCD beyond the first year. This study provides fresh evidence of SCD assessment for improving risk stratification of HT recipients. Funding Acknowledgement Type of funding source: None
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    URL: Article
    DOI: 10.1093/ehjci/ehaa946.1110
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2001908-7
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  • 5
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    Determinants of trajectories of cardiac allograft vasculopathy after heart transplantation: a population based study
    Oxford University Press (OUP) ; 2020
    In:  European Heart Journal Vol. 41, No. Supplement_2 ( 2020-11-01)
    Details
    In: European Heart Journal, Oxford University Press (OUP), Vol. 41, No. Supplement_2 ( 2020-11-01)
    Abstract: Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. Little is known about determinants of CAV trajectories at a population level. Purpose We aimed to identify the respective contribution of immune and non-immune factors in the different evolutive profiles of CAV. Methods Heart transplant recipients receiving care at 2 academic centers (2004 to 2016) were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The outcome was CAV trajectories, identified with unsupervised latent class mixed models. The independent, predictive factors of CAV trajectories were investigated with multinomial regressions (NCT04117152). Results Overall, 815 patients were included. The median follow-up post-transplant was 7.7 years (IQR=5.14) with 2,742 coronary angiographies analyzed. We identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i) Patients without CAV at baseline and non-progression (n=459, 56.3%), ii) patients without CAV at baseline and late onset CAV progression (n=62, 7.6%), iii) patients with mild baseline CAV and mild progression (n=188 23.1%), iv) patients with mild baseline CAV and accelerated CAV progression (n=106, 13.0%, discrimination 0.92). Six early independent predictors of CAV trajectories were identified: donor age (p & lt;0.001), donor male gender (p & lt;0.001), donor tobacco consumption (p=0.001), recipient post-transplant dyslipidemia (p=0.009), preexisting or de novo class II anti-HLA donor-specific antibodies (p=0.004) and episode of acute cellular rejection ≥2R during the first year post transplantation (p=0.028). Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 robust CAV trajectories and their respective immune and non-immune determinants. Our results provide the basis for a trajectory-based assessment of heart transplant patients for early patient risk stratification and patient monitoring. Factors associated CAV trajectories in multivariate analyses in the derivation cohort. This table shows the association of clinical, immunological, functional and structural parameters associated with CAV trajectories in multivariate multinomial regression analysis. The trajectory of reference was trajectory #1, including patients with no CAV at baseline and stable CAV grade over time. Funding Acknowledgement Type of funding source: None
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    URL: Article
    DOI: 10.1093/ehjci/ehaa946.1288
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2001908-7
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  • 6
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    Identification of trajectories of cardiac allograft vasculopathy after heart transplantation: a nationwide comparison
    Oxford University Press (OUP) ; 2020
    In:  European Heart Journal Vol. 41, No. Supplement_2 ( 2020-11-01)
    Details
    In: European Heart Journal, Oxford University Press (OUP), Vol. 41, No. Supplement_2 ( 2020-11-01)
    Abstract: Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient's mortality. However, little is known about CAV trajectories at a population level. Purpose We aimed to identify the different profiles of CAV trajectories. Methods Heart transplant recipients receiving care at 4 academic centers (2004 to 2016) were included. Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessment of clinical, functional, histological and immunological parameters. The mainoutcome was the CAV trajectories, identified with unsupervised latent class mixed models. Results Overall, 1,301 patients were included (609 in France, 206 in Belgium and 486 in the US). The median follow-up post-transplant was 6.6 years (IQR=4.7) with 4,710 coronary angiographies analyzed (3.6±1.6 CAV assessments per patient). In the French development cohort, we identified 4 distinct profiles of CAV trajectories over 10 years that were characterized by i) Patients without CAV at baseline and non-progression (n=317, 52.1%), ii) patients without CAV at baseline and late onset CAV progression (n=52, 8.5%), iii) patients with mild baseline CAV and mild progression (n=151, 24.8%), iv) patients with mild baseline CAV and accelerated CAV progression (n=89, 14.6%, discrimination 0.92). The 4 CAV trajectories were independently validated in the external validation cohorts from Belgium (discrimination=0.92) and the US (discrimination=0.97). Conclusion In a large multicentric and highly phenotyped prospective cohort of heart transplant recipients, we identified and validated 4 distinct CAV trajectories corresponding to specific initial CAV grades and subsequent evolutions. Our results provide the basis for a trajectory-based assessment for risk stratification at early-stage post heart transplantation. Figure 1. Cardiac allograft vasculopathy trajectories in France (n=609), in Belgium (n=206), in USA (n=486). Thick lines represent latent class trajectory; thin lines represent CAV individual patient trajectory. Funding Acknowledgement Type of funding source: None
    Type of Medium: Online Resource
    ISSN: 0195-668X , 1522-9645
    URL: Article
    DOI: 10.1093/ehjci/ehaa946.2696
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2001908-7
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