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Aims The epidemiology of sudden cardiac death (SCD) after heart transplantation (HTx) remains imprecisely described. We aimed to assess the incidence and determinants of SCD in a large cohort of HTx recipients, compared with the general population. Methods and results Consecutive HTx recipients (n = 1246, 2 centres) transplanted between 2004 and 2016 were included. We prospectively assessed clinical, biological, pathologic, and functional parameters. SCD was centrally adjudicated. We compared the SCD incidence beyond the first year post-transplant in this cohort with that observed in the general population of the same geographic area (registry carried out by the same group of investigators; n = 19 706 SCD). We performed a competing risk multivariate Cox model to identify variables associated with SCD. The annual incidence of SCD was 12.5 per 1,000 person-years [95% confidence interval (CI), 9.7–15.9] in the HTx recipients cohort compared with 0.54 per 1,000 person-years (95% CI, 0.53–0.55) in the general population (P < 0.001). The risk of SCD was markedly elevated among the youngest HTx recipients with standardized mortality ratios for SCD up to 837 for recipients ≤30 years. Beyond the first year, SCD was the leading cause of death. Five variables were independently associated with SCD: older donor age (P = 0.003), younger recipient age (P = 0.001) and ethnicity (P = 0.034), pre-existing donor-specific antibodies (P = 0.009), and last left ventricular ejection fraction (P = 0.048). Conclusion HTx recipients, particularly the youngest, were at very high risk of SCD compared with the general population. The consideration of specific risk factors may help identify high-risk subgroups.

Background: Carmat bioprosthetic total artificial heart (Aeson; A-TAH) is a pulsatile and autoregulated device. The aim of this study is to evaluate level of hemolysis potential acquired von Willebrand syndrome after A-TAH implantation. Methods: We examined the presence of hemolysis and acquired von Willebrand syndrome in adult patients receiving A-TAH support (n=10) during their whole clinical follow-up in comparison with control subjects and adult patients receiving Heartmate II or Heartmate III support. We also performed a fluid structure interaction model coupled with computational fluid dynamics simulation to evaluate the A-TAH resulting shear stress and its distribution in the blood volume. Results: The cumulative duration of A-TAH support was 2087 days. A-TAH implantation did not affect plasma free hemoglobin over time, and there was no association between plasma free hemoglobin and cardiac output or beat rate. For VWF (von Willebrand factor) evaluation, A-TAH implantation did not modify multimers profile of VWF in contrast to Heartmate II and Heartmate III. Furthermore, fluid structure interaction coupled with computational fluid dynamics showed a gradually increase of blood damage according to increase of cardiac output ( P Conclusions: We demonstrated that A-TAH does not cause hemolysis or AWVS. However, relationship between HMWM and cardiac output depending flow confirms relevance of VWF as a biological sensor of blood flow, even in normal range.

Aims Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various causes that may influence prognosis. Methods and results We extracted the electronic medical records for 2180 consecutive patients hospitalized between 2016 and 2019 for decompensated heart failure. Using a text mining algorithm looking for a left ventricular ejection fraction ≥50% and plasma brain natriuretic peptide level >100 pg/mL, we identified 928 HFpEF patients. We screened for a prevailing cause of HFpEF according to European guidelines and found that 418 (45.0%) patients had secondary HFpEF due to either myocardial (n = 125, 13.5%) or loading condition abnormalities (n = 293, 31.5%), while the remaining 510 (55.0%) patients had idiopathic HFpEF. We assessed the association between the causes of HFpEF and survival collected up to 31 December 2020 using Cox proportional hazards analysis. Even though patients with idiopathic HFpEF were older, frequently female, and had frequent co‐morbidities and a higher crude mortality rate compared with secondary HFpEF patients, their prognosis was similar after adjustment for age and sex. Unsupervised clustering analysis revealed three main phenogroups with different distribution of idiopathic vs. secondary HFpEF. The phenogroup with the highest proportion of idiopathic HFpEF (69%) had (i) an excess rate of non‐cardiac co‐morbidities including chronic obstructive pulmonary disease (31%) or obesity (41%) and (ii) a better prognosis compared with the two other phenogroups enriched with secondary HFpEF. Conclusions Aetiological classification provides clinical and prognostic information and may be useful to better decipher the clinical heterogeneity of HFpEF., Condensed abstract The identification of specific aetiologies was possible in almost half of patients with heart failure with preserved ejection fraction (HFpEF). Compared with patients with secondary HFpEF, patients with idiopathic HFpEF were older, frequently female, and had a higher proportion of co‐morbidities and high crude mortality rates, but their prognosis was similar after adjustment for age and sex. Unsupervised cluster analysis, however, indicated that idiopathic HFpEF patients were mostly grouped into separate cluster with a better prognosis. Aetiological classification provides clinical and prognostic information and may be useful to better decipher the clinical heterogeneity of HFpEF.

Resume L’hydroxychloroquine (HCQ) est consideree comme un traitement efficace et sur du lupus systemique. Nous presentons un cas de cardiomyopathie toxique fatale, complication sous-estimee du traitement par HCQ. Une femme de 72 ans presentant un lupus systemique et traitee par HCQ pendant 24 ans a ete transplantee avec un greffon renal. Un an apres elle a developpe une cardiomyopathie avec des troubles de la conduction. Une biopsie endomyocardique a mis en evidence une fibrose myocardique severe non specifique et une hypertrophie myocytaire avec des myocytes vacuolises. L’analyse en microscopie electronique a transmission a montre des inclusions curvilineaires et des figures pseudomyeliniques compatibles avec une cardiomyopathie toxique a l’HCQ. L’immunohistochimie a revele une accumulation de LC3b, p62 et becline-1 dans les vacuoles des myocytes cardiaques suggerant une alteration des processus d’autophagie. La survenue d’une cardiopathie non expliquee chez des patients traites au long cours par HCQ doit faire rechercher une cardiomyopathie toxique et indiquer une biopsie endomyocardique.

Left ventricular assist device (LVAD) implantation may be an attractive alternative therapeutic option for elderly patients with heart failure who are ineligible for heart transplantation.We aimed to describe the characteristics and outcomes of elderly patients (i.e. aged≥70 years) receiving an LVAD.This observational study was conducted in 19 centres between 2006 and 2016. Patients were divided into two groups-younger (aged70 years) and elderly (aged≥70 years), based on age at time of LVAD implantation.A total of 652 patients were included in the final analysis, and 74 patients (11.3%) were aged≥70 years at the time of LVAD implantation (maximal age 77.6 years). The proportion of elderly patients receiving an LVAD each year was constant, with a median of 10.6% (interquartile range 8.0-15.4%) per year, and all were implanted as destination therapy. Elderly and younger patients had similar durations of hospitalization in intensive care units and total lengths of hospital stays. Both age groups experienced similar rates of LVAD-related complications (i.e. stroke, bleeding, driveline infection and LVAD exchange), and the occurrence of LVAD complications did not impact survival in the elderly group compared with the younger group. Lastly, when compared with younger patients implanted as destination therapy, the elderly group also exhibited similar mid-term survival.This work strongly suggests that selected elderly adults can be scheduled for LVAD implantation.

Background: Cardiac allograft vasculopathy (CAV) is a major contributor of heart transplant recipient mortality. Little is known about the prototypes of CAV trajectories at the population level. We aimed to identify the different evolutionary profiles of CAV and to determine the respective contribution of immune and nonimmune factors in CAV development. Methods: Heart transplant recipients were from 4 academic centers (Pitié-Salpêtrière and Georges Pompidou Hospital, Paris, Katholieke Universiteit Leuven, and Cedars-Sinai, Los Angeles; 2004–2016). Patients underwent prospective, protocol-based monitoring consisting of repeated coronary angiographies together with systematic assessments of clinical, histological, and immunologic parameters. The main outcome was a prediction for CAV trajectory. We identified CAV trajectories by using unsupervised latent class mixed models. We then identified the independent predictive variables of the CAV trajectories and their association with mortality. Results: A total of 1301 patients were included (815 and 486 in the European and US cohorts, respectively). The median follow-up after transplantation was 6.6 (interquartile range, 4–9.1) years with 4710 coronary angiographies analyzed. We identified 4 distinct profiles of CAV trajectories over 10 years. The 4 trajectories were characterized by (1) patients without CAV at 1 year and nonprogression over time (56.3%), (2) patients without CAV at 1 year and late-onset slow CAV progression (7.6%), (3) patients with mild CAV at 1 year and mild progression over time (23.1%), and (4) patients with mild CAV at 1 year and accelerated progression (13.0%). This model showed good discrimination (0.92). Among candidate predictors assessed, 6 early independent predictors of these trajectories were identified: donor age ( P P P =0.001), recipient dyslipidemia ( P =0.009), class II anti–human leukocyte antigen donor-specific antibodies ( P =0.004), and acute cellular rejection ≥2R ( P =0.028). The 4 CAV trajectories manifested consistently in the US independent cohort with similar discrimination (0.97) and in different clinical scenarios, and showed gradients for overall-cause mortality ( P Conclusions: In a large multicenter and highly phenotyped prospective cohort of heart transplant recipients, we identified 4 CAV trajectories and their respective independent predictive variables. Our results provide the basis for a trajectory-based assessment of patients undergoing heart transplantation for early risk stratification, patient monitoring, and clinical trials. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04117152.

International audience; LVAD implantation in patients with a recently diagnosed cardiomyopathy has been poorly investigated. This work aims at describing the characteristics and outcomes of patients receiving a LVAD within 30 days following the diagnosis of cardiomyopathy. Patients from the ASSIST-ICD study was divided into recently and remotely diagnosed cardiomyopathy based on the time from initial diagnosis of cardiomyopathy to LVAD implantation using the cut point of 30 days. The primary end point of the study was all-cause mortality at 30-day and during follow-up. A total of 652 patients were included and followed during a median time of 9.1 (2.5 to 22.1) months. In this population, 117 (17.9%) had a recently diagnosed cardiomyopathy and had LVAD implantation after a median time of 15.0 (9.0 to 24.0) days following the diagnosis. This group of patients was significantly younger, with more ischemic cardiomyopathy, more sudden cardiac arrest (SCA) events at the time of the diagnosis and were more likely to receive temporary mechanical support before LVAD compared with the remotely diagnosed group. Postoperative in-hospital survival was similar in groups, but recently diagnosed patients had a better long-term survival after hospital discharge. SCA before LVAD and any cardiac surgery combined with LVAD implantation were identified as 2 independent predictors of postoperative mortality in recently diagnosed patients. In conclusion, rescue LVAD implantation for recently diagnosed severe cardiomyopathy is common in clinical practice. Such patients experience a relatively low postoperative mortality and have a better long-term survival compared with remotely diagnosed patients.

OBJECTIVES Right ventricular failure after left ventricular assist device (LVAD) insertion is associated with significant mortality and morbidity. Mechanical support options include right ventricular assist devices, venoarterial extracorporeal membrane oxygenation (ECMO) and venopulmonary artery ECMO, the latter often involving central cannulation. We sought to evaluate the feasibility and early outcomes of a truly percutaneous venopulmonary artery (pVPA) ECMO strategy, with the potential advantage of bedside removal once weaned. METHODS Data from a single tertiary centre were reviewed retrospectively from January 2014 to January 2019. During this time, 54 patients underwent LVAD insertion, with 19 requiring mechanical support for right ventricular failure. Among them, 10 patients received pVPA ECMO. Implantation of the pVPA ECMO was performed under transoesophageal echocardiography and fluoroscopy guidance, with an inflow cannula placed in the right atrium via the right femoral vein and an outflow cannula placed in the left pulmonary artery (PA) via the right internal jugular vein. RESULTS Cannula insertion was 100% successful with no need for repositioning. Eight patients (80%) were able to be successfully weaned (at the bedside); 6 were discharged from the hospital and there were no cases of early sepsis, mediastinitis or thromboembolism. At follow-up, 5 patients had received transplants (50%), with 1 on LVAD support as destination therapy (10%). Survival was 60 ± 15% and 50 ± 16% at 6 and 12 months, respectively. CONCLUSIONS pVPA ECMO is 100% technically feasible and is an efficient method for temporary right ventricular support after LVAD insertion with the advantage of simple bedside removal and avoidance of a PA graft remnant in the chest cavity.

Since the earliest cases of coronavirus disease 2019 (COVID-19) infection were reported, our care delivery systems have been reorganized and challenged in unprecedent ways, specifically the cardiovascular community. COVID-19 poses a challenge for heart transplantation, affecting donor selection, immunosuppression, and posttransplant management. Left Ventricular Assist Device (LVAD) therapy is currently a viable option for patients with end-stage heart failure as a bridge to heart transplantation or destination therapy. Here, we present a therapeutic strategy for the management of acute HF with Intermacs profiles from 1 to 4, with or without Covid-19 infection, exemplified by serie of patients presenting with severe HF and successfully treated by LVAD therapy during the spread of the Covid-19 pandemic and the French national lockdown. This experience has shown that we still have the capacity to provide the right therapy for the right disease to the right patient. LVAD implantation seems to be the treatment of choice for advanced HF due to the lack of healthy donor hearts for cardiac transplantation. Covid or non-Covid context, we have to take care of our patients with end-stage HF the best we can.

Background 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

Background 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

Background 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 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

Background 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 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

International audience; We aimed at characterizing the impact of low and high body mass index (BMI) on outcomes after left-ventricular assist device (LVAD) surgery and define the predictors of mortality in patients with abnormal BMI (low/high). This study was conducted in 19 centers from 2006 to 2016. Patients were divided based on their baseline BMI into 3 groups of BMI: low (BMI ≤18.5 kg/m²); normal (BMI = 18.5 to 24.99 kg/m²) and high (BMI ≥25 kg/m²) (including overweight (BMI = 25 to 29.99 kg/m²), and obesity (BMI ≥30 Kg/m²)). Among 652 patients, 29 (4.4%), 279 (42.8%) and 344 (52.8%) had a low-, normal-, and high BMI, respectively. Patients with high BMI were significantly more likely men, with more co-morbidities and more history of ventricular/supra-ventricular arrhythmias before LVAD implantation. Patients with abnormal BMI had significantly lower survival than those with normal BMI. Notably, those with low BMI experienced the worst survival whereas overweight or obese patients had similar survival. Four predictors of mortality for LVAD candidates with abnormal BMI were defined: total bilirubin ≥16 µmol/L before LVAD, hypertension, destination therapy, and cardiac surgery with LVAD. Depending on the number of predictor per patients, those with abnormal BMI may be divided in 3 groups of 1-year mortality risk, i.e., low (0 to 1 predictor: 29% and 31%), intermediate (2 to 3 predictors, 51% and 52%, respectively), and high (4 predictors: 83%). In conclusion, LVAD recipients with abnormal BMI experience lower survival, especially underweight patients. Four predictors of mortality have been identified for LVAD population with abnormal BMI, differentiating those a low-, intermediate-, and high risks of death.

Hydroxychloroquine (HCQ) is considered as efficient and safe to treat systemic lupus. We report a case of fatal toxic cardiomyopathy, an underrecognized adverse effect of HCQ. A 72-year-old woman with systemic lupus erythematosus treated for 24 years by HCQ received a kidney allograft. One year later she developed a cardiomyopathy with conductive disorders. An endomyocardial biopsy showed severe non-specific myocardial fibrosis and hypertrophic vacuolated myocytes. Transmission electron microscopy showed curvilinear bodies and pseudomyelin figures consistent with HCQ-induced cardiomyopathy. At immunohistochemistry LC3b, p62 and beclin-1 accumulated in vacuolated cardiac myocytes suggesting impaired cell autophagy. When unexplained cardiac disease develops in patients receiving long-term HCQ treatment, toxic cardiomyopathy should be considered leading to a diagnostic endomyocardial biopsy.

Background 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 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

Background The benefits of available automatic external defibrillators (AEDs) for out-of-hospital cardiac arrests (OHCAs) are well known, but strategies for their deployment outdoors remain somewhat arbitrary. Our study sought to assess different strategies for AED deployment. Methods All OHCAs in Paris between 2000 and 2010 were prospectively recorded and geocoded. A guidelines-based strategy of placing an AED in locations where more than one OHCA had occurred within the past five years was compared to two novel strategies: a grid-based strategy with a regular distance between AEDs and a landmark-based strategy. The expected number of AEDs necessary and their median (IQR) distance to the nearest OHCA were assessed for each strategy. Results Of 4176 OHCAs, 1372 (33%) occurred in public settings. The first strategy would result in the placement of 170 AEDs, with a distance to OHCA of 416 (180–614) m and a continuous increase in the number of AEDS. In the second strategy, the number of AEDs and their distance to the closest OHCA would change with the grid size, with a number of AEDs between 200 and 400 seeming optimal. In the third strategy, median distances between OHCAs and AEDs would be 324m if placed at post offices (n=195), 239 at subway stations (n=302), 137 at bike-sharing stations (n=957), and 142 at pharmacies (n=1466). Conclusion This study presents an original evidence-based approach to strategies of AED deployment to optimize their number and location. This rational approach can estimate the optimal number of AEDs for any city.

International audience; Objectives - This study aimed to evaluate incidence, clinical significance, and predictors of early ventricular arrhythmias (VAs) in left ventricular assist device (LVAD) recipients. Background - LVAD implantation is increasingly used in patients with end-stage heart failure. Early VAs may occur during the 30-day post-operative period, but many questions remain unanswered regarding their incidence and clinical impact. Methods - This observational study was conducted in 19 centers between 2006 and 2016. Early VAs were defined as sustained ventricular tachycardia and/or ventricular fibrillation occurring

International audience; Background - Ventricular arrhythmias (VAs) can occur after continuous flow left ventricular assist device (LVAD) implantation as a single arrhythmic event or as electrical storm (ES) with multiple repetitive VA episodes. Objective - We aimed at analyzing the incidence, predictors, and clinical impact of ES in LVAD recipients. Methods - Patients analyzed were those included in the multicenter ASSIST-ICD observational study. ES was consensually defined as occurrence of ≥3 separate episodes of sustained VAs within a 24-hour interval. Results - Of 652 patients with an LVAD, 61 (9%) presented ES during a median follow-up period of 9.1 (interquartile range [IQR] 2.5-22.1) months. The first ES occurred after 17 (IQR 4.0-56.2) days post LVAD implantation, most of them during the first month after the device implantation (63%). The incidence then tended to decrease during the initial years of follow-up and increased again after the third year post LVAD implantation. History of VAs before LVAD implantation and heart failure duration > 84 months were independent predictors of ES. The occurrence of ES was associated with an increased early mortality since 20 patients (33%) died within the first 2 weeks of ES. Twenty-two patients (36.1%) presented at least 1 recurrence of ES, occurring 43.0 (IQR 8.0-69.0) days after the initial ES. Patients experiencing ES had a significantly lower 1-year survival rate than did those free from ES (log-rank, P = .039). Conclusion - There is a significant incidence of ES in patients with an LVAD. The short-term mortality after ES is high, and one-third of patients will die within 15 days. Whether radiofrequency ablation of arrhythmias improves outcomes would require further studies.

The frequency, characteristics and outcomes of primary prevention implantable cardioverter defibrillator (ICD) recipients who eventually undergo heart transplantation (HT) during follow-up have not been well described.In a cohort of patients with heart failure implanted with an ICD for primary prevention of sudden cardiac death, to identify those at high risk of subsequent HT and evaluate ICD usefulness.Between 2002 and 2012, 5539 patients received a primary prevention ICD across 12 centers, and were enrolled in the DAI-PP programme, including 5427 with full HT information available.During a median follow-up of 1024 days (interquartile range 484-1702 days), 176 (3.2%) patients underwent HT. Median duration between ICD implantation and HT was 484 days (IQR 169-1117 days). Among those aged≤65 years (theoretical age limit for HT registration in France), the overall incidence per 1000 person-years was 18.03 (95% confidence interval [CI]: 15.32-20.74). Left ventricular ejection fraction25% (hazard ratio [HR]: 3.43, 95% CI: 2.34-5.04; P0.0001), younger age (HR: 0.95, 95% CI: 0.93-0.96; P0.0001), New York Heart Association (NYHA) class III-IV (HR: 2.67, 95% CI: 1.79-4.00; P0.0001) and no cardiac resynchronization therapy (HR: 2.09, 95% CI: 1.39-3.14; P=0.0004) were independently associated with HT. Patients with these three characteristics (excluding age) had a 1-year HT rate of 15.2%. Incidence of appropriate ICD therapies was 92.7 per 1000 person-years for patients who underwent HT versus 76.1 for those who did not (P=0.64).The overall incidence of HT in this primary prevention population was relatively high, especially among young patients with a very low ejection fraction, an advanced NYHA class and were unsuitable for cardiac resynchronization therapy (up to 15% annually). Patients awaiting HT experienced a significant rate of appropriate ICD therapies, reinforcing the importance of specific cardiac rhythm management in these patients.

Background 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). A total of 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 intensive car unit. Beyond the post-operative 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) ( Fig. 1 ). 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.

In heart transplantation, there is a lack of robust evidence of the specific causes of late allograft failure. We hypothesized that a substantial fraction of failing heart allografts may be associated with antibody-mediated injury and immune-mediated coronary arteriosclerosis. We included all patients undergoing a retransplantation for late terminal heart allograft failure in three referral centers. We performed an integrative strategy of heart allograft phenotyping by assessing the heart vascular tree including histopathology and immunohistochemistry together with circulating donor-specific antibodies. The main analysis included 40 explanted heart allografts patients and 402 endomyocardial biopsies performed before allograft loss. Overall, antibody-mediated rejection was observed in 19 (47.5%) failing heart allografts including 16 patients (40%) in whom unrecognized previous episodes of subclinical antibody-mediated rejection occurred 4.5 ± 3.5 years before allograft loss. Explanted allografts with evidence of antibody-mediated rejection demonstrated higher endothelitis and microvascular inflammation scores (0.89 ± 0.26 and 2.25 ± 0.28, respectively) compared with explanted allografts without antibody-mediated rejection (0.42 ± 0.11 and 0.36 ± 0.09, p = 0.046 and p

International audience; Objectives - This study aimed to evaluate the incidence, clinical impact, and predictors of late ventricular arrhythmias (VAs) in left ventricular assist device (LVAD) recipients aiming to clarify implantable cardioverter-defibrillator (ICD) indications. Background - The arrhythmic risk and need for ICD in patients implanted with an LVAD are not very well known. Methods - This observational study was conducted in 19 centers between 2006 and 2016. Late VAs were defined as sustained ventricular tachycardia or fibrillation occurring >30 days post-LVAD implantation, without acute reversible cause and requiring appropriate ICD therapy, external electrical shock, or medical therapy. Results - Among 659 LVAD recipients, 494 (median 58.9 years of age; mean left ventricular ejection fraction 20.7 ± 7.4%; 73.1% HeartMate II, 18.6% HeartWare, 8.3% Jarvik 2000) were discharged alive from hospital and included in the final analysis. Late VAs occurred in 133 (26.9%) patients. Multivariable analysis identified 6 independent predictors of late VAs: VAs before LVAD implantation, atrial fibrillation before LVAD implantation, idiopathic etiology of the cardiomyopathy, heart failure duration >12 months, early VAs (

We report the case of a patient who had undergone injections of myoblasts in an infarct area 16 years before being referred for heart transplantation. The pathological examination of the explanted heart found persisting myotubes embedded in fibrosis. This finding supports the ability of myoblasts to survive in harsh environments, which can make them appealing candidates for transplantation in diseases requiring supply of new myogenic cells.

Purpose To identify distinct profiles of cardiac allograft vasculopathy (CAV) trajectory and their determinants. Methods We performed a multicenter study (Pitie & HEGP, Paris). We included all patients transplanted between 2004 and 2011 who had at least 2 coronary angiograms during follow-up (n = 436). We performed an comprehensive evaluation of potential risk factors that might be associated with CAV including in-depth characterization of donor-specific antibodies (DSA) and retrospective endomyocardial biopsies reviewing. A semi parametric mixture model was used to identify distinct trajectories of CAV progression from year 1 to year 10 post-transplantation among the 1407 coronary angiograms (3.4±1.4 angiograms per patient). Multivariable logistic regression model was used to determine risk factors associated with each trajectory. Results Median follow-up post-transplant was 7 years. Four latent classes of CAV trajectories were identified: #1-non-progressors (n=240, 55%), #2- late progressors (n=35, 8%), #3- early progressors (n=99, 22.7%) and #4- severe progressors (n = 62, 14.3%, figure). Taking latent class #1 as reference, 5 parameters were associated with CAV progression: donor age (HR = 1.06 and 1.08 per 1-yr increment for latent classes #3 and #4, respectively, p Conclusion In a large and highly phenotyped cohort of heart transplant recipients, we identified 4 distinct prototypes of CAV trajectories. Donor-derived cardiovascular risk factors, 1-year post-transplant cardiovascular profile (dyslipidemia) and immunological parameters (pre-formed DSA) were independent risk factors for CAV severity and progression.

Background: Antibody-mediated rejection (AMR) contributes to heart allograft loss. However, an important knowledge gap remains in terms of the pathophysiology of AMR and how detection of immune activity, injury degree, and stage could be improved by intragraft gene expression profiling. Methods: We prospectively monitored 617 heart transplant recipients referred from 4 French transplant centers (January 1, 2006–January 1, 2011) for AMR. We compared patients with AMR (n=55) with a matched control group of 55 patients without AMR. We characterized all patients using histopathology (ISHLT [International Society for Heart and Lung Transplantation] 2013 grades), immunostaining, and circulating anti-HLA donor-specific antibodies at the time of biopsy, together with systematic gene expression assessments of the allograft tissue, using microarrays. Effector cells were evaluated with in vitro human cell cultures. We studied a validation cohort of 98 heart recipients transplanted in Edmonton, AB, Canada, including 27 cases of AMR and 71 controls. Results: A total of 240 heart transplant endomyocardial biopsies were assessed. AMR showed a distinct pattern of injury characterized by endothelial activation with microcirculatory inflammation by monocytes/macrophages and natural killer (NK) cells. We also observed selective changes in endothelial/angiogenesis and NK cell transcripts, including CD16A signaling and interferon-γ–inducible genes. The AMR-selective gene sets accurately discriminated patients with AMR from those without and included NK transcripts (area under the curve=0.87), endothelial activation transcripts (area under the curve=0.80), macrophage transcripts (area under the curve=0.86), and interferon-γ transcripts (area under the curve=0.84; P P + ) and full-blown pAMR2/3 cases. Endothelial activation transcripts, interferon-γ, and NK transcripts showed association with chronic allograft vasculopathy. The molecular architecture and selective AMR transcripts, together with gene set discrimination capacity for AMR identified in the discovery set, were reproduced in the validation cohort. Conclusions: Tissue-based measurements of specific pathogenesis-based transcripts reflecting NK burden, endothelial activation, macrophage burden, and interferon-γ effects accurately classify AMR and correlate with degree of injury and disease activity. This study illustrates the clinical potential of a tissue-based analysis of gene transcripts to refine diagnosis of heart transplant rejection.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Authors. This abstract has been published due to a miscommunication in the ANZSCTS ASM conference supplement. It needs to be retracted as we the authors wish to submit a full length paper with updated material.