Search

Background: Percutaneous coronary intervention (PCI) might improve outcome at severe stages of cardiac allograft vasculopathy (CAV) among patients after heart transplantation (HTx). Yet, risk stratification of HTx patients after PCI remains challenging., Aims: To assess whether the International Society for Heart and Lung Transplantation (ISHLT) CAV classification remains prognostic after PCI and whether risk-stratification models of non-transplanted patients extend to HTx patients with CAV., Methods: At 2 European academic centers, 203 patients were stratified in cohort 1 (ISHLT CAV1, without PCI, n = 126) or cohort 2 (ISHLT CAV2 and 3, with PCI). At first diagnosis of CAV or first PCI, respectively, ISHLT CAV grades, SYNTAX scores I and II (SXS-I, SXS-II) were used to quantify baseline and residual CAV (rISHLT, rSXS-I, rSXS-II). RSXS-I > 0 defined incomplete revascularization (IR)., Results: SXS-II predicted mortality in cohort 1 (P = 0.004), whereas SXS-I (P = 0.009) and SXS-II (P = 0.002) predicted mortality in cohort 2. Post-PCI, IR (P = 0.004), high rISHLT (P = 0.02) and highest tertile of rSXS-II (P = 0.006) were associated with higher 5-year mortality. In bivariable Cox analysis, baseline SXS-II, IR and rSXS-II remained predictors of 5-year mortality post-PCI. There was a strong inverse relationship between baseline and rSXS-I (r = -0.55; P < 0.001 and r = -0.50; P = 0.003, respectively) regarding the interval to first reintervention., Conclusion: People with ISHLT CAV classification could apply for risk stratification after PCI. SYNTAX scores could be complemental for risk stratification and individualization of invasive follow-up of HTx patients with CAV., Competing Interests: Disclosures DB reports speaker honoraria from Abbott Vascular outside the submitted work. JH reports grants and personal fees from Abbott Vascular and Edwards Lifescience outside the submitted work. A-CM reports grants and consulting fees from Bristol Myers Squibb, Bayer outside the submitted work. SU reports grants from Novartis and Astellas Pharma outside the submitted work. JM reports lecture fees from Daiichi Sankyo, SIS Medical, Biotronik, Astra Zeneca, and Bristol Myers Squibb outside the submitted work. SM reports grants from German Federal Ministry of Education and Research/German Centre for Cardiovascular Research, grants from German Research Foundation, grants from Boston Scientific and Foundation Leducq Transatlantic Network of Excellence outside the submitted work. All other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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 <0.01), however, the blood volume fraction that endured significant shear stresses was always inferior to 0.03% of the volume for both ventricles in all regimens tested. An inverse association between cardiac output, beat rate, and high-molecular weight multimers ratio was found., 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., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Despite regularly updated guidelines, there is still a delay in referral of advanced heart failure patients to mechanical circulatory support and transplant centres. We aimed to analyse characteristics and outcome of non-inotrope-dependent patients implanted with a left ventricular assist device (LVAD)., Methods and Results: The ASSIST-ICD registry collected LVAD data in 19 centres in France between February 2006 and December 2016. We used data of patients in Interagency Registry for Mechanically Assisted Circulatory Support Classes 4-7. The primary endpoint was survival analysis. Predictors of mortality were searched with multivariable analyses. A total of 303 patients (mean age 61.0 ± 9.9 years, male sex 86.8%) were included in the present analysis. Ischaemic cardiomyopathy was the leading heart failure aetiology (64%), and bridge to transplantation was the main implantation strategy (56.1%). The overall likelihood of being alive while on LVAD support or having a transplant at 1, 2, 3, and 5 years was 66%, 61.7%, 58.7%, and 55.1%, respectively. Age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.00-1.05; P = 0.02], a concomitant procedure (HR 2.32, 95% CI 1.52-3.53; P < 0.0001), and temporary mechanical right ventricular support during LVAD implantation (HR 2.94, 95% CI 1.49-5.77; P = 0.002) were the only independent variables associated with mortality. Heart failure medications before or after LVAD implantation were not associated with survival., Conclusion: Ambulatory heart failure patients displayed unsatisfactory survival rates after LVAD implantation. A better selection of patients who can benefit from LVAD may help improving outcomes., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Atrioventricular regurgitation is frequent in the setting of heart failure. It is due to atrial and ventricular remodelling, as well as rhythmic disturbances and loss of synchrony. Once atrioventricular regurgitation develops, it can aggravate the underlying heart failure, and further participate and aggravate its own severity. Its presence is therefore concomitantly a surrogate of advance disease and a predictor of mortality. Heart failure management, including medical therapy, cardiac resynchronization therapy, and restoration of sinus rhythm, are the initial steps to reduce atrioventricular regurgitation. In the current review, we analyse the current data assessing the epidemiology, pathophysiology, and impact of non-valvular intervention on atrioventricular regurgitation including medical treatment, cardiac resynchronization and atrial fibrillation ablation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Martin, Bories, Tence, Baudinaud, Pechmajou, Puscas, Marijon, Achouh and Karam.)

Background: Sensitized patients, i.e. recipients with preformed donor-specific HLA antibodies (pfDSA), are at high-risk of developing antibody-mediated rejections (AMR) and dying after heart transplantation (HTx). Perioperative desensitization procedures are associated with better outcomes but can cause sensitization, which may influence their efficacy., Methods: In sensitized patients (pfDSA>1000 mean immunofluorescence (MFI) units), we assessed the effect of perioperative desensitization by comparing treated patients to a historical control cohort. Multivariable survival analyses were performed on the time to main outcome, a composite of death and biopsy-proven AMR with 5-year follow-up., Results: The study included 68 patients: 31 control and 37 treated patients. There was no difference in preoperative variables between the two groups, including cumulative pfDSA [4026 (1788;8725) vs 4560 (3162;13392) MFI units, p =0.28]. The cause of sensitization was pregnancy in 24/68, 35.3%, transfusion in 61/68, 89.7%, and previous HTx in 4/68, 5.9% patients. Multivariable analysis yielded significant protective association between desensitization and events (adjusted (adj.) hazard ratio (HR)=0.44 (95% confidence interval (95CI)=0.25-0.79), p =0.006) and deleterious association between cumulative pfDSA and events [per 1000-MFI increase, adj.HR=1.028 (1.002-1.053), p=0.031]. There was a sex-difference in the efficacy of desensitization: in men (n=35), the benefit was significant [unadj.HR=0.33 (95CI=0.14-0.78); p=0.01], but not in women (n=33) [unadj.HR=0.52 (0.23-1.17), p=0.11]. In terms of the number of patients treated, in men, 2.1 of patients that were treated prevented 1 event, while in women, 3.1 required treatment to prevent 1 event., Conclusion: Perioperative desensitization was associated with fewer AMR and deaths after HTx, and efficacy was more pronounced in men than women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nguyen, Salem, Bories, Coutance, Amour, Bougle, Suberbielle, Kheav, Carmagnat, Rouvier, Kirsch, Varnous, Leprince and Saheb.)

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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Competing Interests: Les auteurs déclarent n'avoir aucun lien d'intérêts.

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., (Published on behalf of the European Society of Cardiology. © The Author(s) 2020.)

Background: 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., Aim: We aimed to describe the characteristics and outcomes of elderly patients (i.e. aged≥70 years) receiving an LVAD., Methods: This observational study was conducted in 19 centres between 2006 and 2016. Patients were divided into two groups-younger (aged<70 years) and elderly (aged≥70 years), based on age at time of LVAD implantation., Results: 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., Conclusion: This work strongly suggests that selected elderly adults can be scheduled for LVAD implantation., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Medsounds™ software allows to create an auscultation learning platform, by providing real pre-recorded cardiopulmonary sounds on virtual chests. The study aimed at comparing the skills in cardiopulmonary auscultation between students who benefited from this platform and students who did not have access to it., Methods: A controlled trial was conducted with 2nd year medical students randomised into three groups. Groups A, B and C received 10 h of cardiopulmonary clinical training. In addition, group B benefited from an online access to the educative platform, and group C had a demonstration of the platform during their clinical training, then an online access. The main outcome was a 3-point multiple-choice questionnaire based on 2 original case vignettes about the description of cardiopulmonary sounds. The secondary outcome was the faculty exam on high-fidelity cardiopulmonary simulator., Results: Groups A and B included 127 students, and group C 117. Students in group C had a significantly higher score than those in group A (1.72/3 versus 1.48/3; p = 0.02), without difference between the groups B and C. Students who actually had a demonstration of the platform and used it at home had a higher score than those who did not use it (1.87 versus 1.51; p = 0.01). Students who had a demonstration of the platform before using it performed a better pulmonary examination on high-fidelity simulators., Conclusion: The supervised use of an online auscultation simulation software in addition to the traditional clinical training seems to improve the auscultation performances of undergraduated medical students., (Copyright © 2020. Published by Elsevier Masson SAS.)

Objectives: Our goal was to provide a picture of left ventricular assist device (LVAD) activity in France between 2007 and 2016 based on the multicentric ASSIST-ICD registry., Methods: We retrospectively collected 136 variables including in-hospital data, follow-up survival rates and adverse events from 671 LVAD recipients at 20 out of 24 LVAD implant centres in France. The average follow-up time was 1.2 years (standard deviation: 1.4); the total follow-up time was 807.5 patient-years., Results: The included devices were the HeartMate II®, HeartWare LVAS® or Jarvik 2000®. The overall likelihood of being alive while on LVAD support or having a transplant (primary end point) at 1, 2, 3 and 5 years postimplantation was 65.2%, 59.7%, 55.9% and 47.7%, respectively, given a cumulative incidence of 29.2% of receiving a transplant at year 5. At implantation, 21.5% of patients were on extracorporeal life support. The overall rate of cardiogenic shock at implantation was 53%. The major complications were driveline infection (26.1%), pump pocket or cannula infection (12.6%), LVAD thrombosis (12.2%), ischaemic (12.8%) or haemorrhagic stroke (5.4%; all strokes 18.2%), non-cerebral haemorrhage (9.1%) and LVAD exchange (5.2%). The primary end point (survival) was stratified by age at surgery and by the type of device used, with inference from baseline profiles. The primary end point combined with an absence of complications (secondary end point) was also stratified by device type., Conclusions: The ASSIST-ICD registry provides a real-life picture of LVAD use in 20 of the 24 implant centres in France. Despite older average age and a higher proportion of patients chosen for destination therapy, survival rates improved compared to those in previous national registry results. This LVAD registry contrasts with other international registries because patients with implants have more severe disease, and the national policy for graft attribution is distinct. We recommend referring patients for LVAD earlier and suggest a discussion of the optimal timing of a transplant for bridged patients (more dismal results after the second year of support?)., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

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 <0.001), donor male sex ( P <0.001), donor tobacco consumption ( 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 <0.001)., 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.

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., (Copyright © 2019. Published by Elsevier Inc.)

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 <30 days post-LVAD implantation and requiring appropriate implantable cardioverter-defibrillator therapy, external electrical shock, or medical therapy., Results: A total of 652 patients (median age: 59.8 years; left ventricular ejection fraction: 20.7 ± 7.4%; HeartMate 2: 72.8%; HeartWare: 19.5%; Jarvik 2000: 7.7%) were included in the analysis. Early VAs occurred in 162 patients (24.8%), most frequently during the first week after LVAD implantation. Multivariable analysis identified history of VAs prior to LVAD and any combined surgery with LVAD as 2 predictors of early VAs. The occurrence of early VAs with electrical storm was the strongest predictor of 30-day post-operative mortality, associated with a 7-fold increase of 30-day mortality. However, in patients discharged alive from hospital, occurrence of early VAs did not influence long-term survival., Conclusions: Early VAs are common after LVAD implantation and increase 30-day post-operative mortality, without affecting long-term survival. Further studies will be needed to analyze whether pre- or pre-operative ablation of VAs may improve post-operative outcomes. (Determination of Risk Factors of Ventricular Arrhythmias After Implantation of Continuous Flow Left Ventricular Assist Device With Continuous Flow Left Ventricular Assist Device [ASSIST-ICD]; NCT02873169)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2019. Published by Elsevier B.V.)

Background: 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., Aims: 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., Methods: 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., Results: 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 fraction<25% (hazard ratio [HR]: 3.43, 95% CI: 2.34-5.04; P<0.0001), younger age (HR: 0.95, 95% CI: 0.93-0.96; P<0.0001), New York Heart Association (NYHA) class III-IV (HR: 2.67, 95% CI: 1.79-4.00; P<0.0001) 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)., Conclusions: 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., (Copyright © 2018. Published by Elsevier Masson SAS.)

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. Stem Cells Translational Medicine 2018;7:705-708., (© 2018 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

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 (<30 days post-LVAD), and no angiotensin-converting enzyme inhibitors during follow-up. The "VT-LVAD score" was created, identifying 4 risk groups: low (score 0 to 1), intermediate (score 2 to 4), high (score 5 to 6), and very high (score 7 to 10). The rates of VAs at 1 year were 0.0%, 8.0%, 31.0% and 55.0%, respectively., Conclusions: Late VAs are common after LVAD implantation. The VT-LVAD score may help to identify patients at risk of late VAs and guide ICD indications in previously nonimplanted patients. (Determination of Risk Factors of Ventricular Arrhythmias [VAs] after implantation of continuous flow left ventricular assist device with continuous flow left ventricular assist device [CF-LVAD] [ASSIST-ICD]; NCT02873169)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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 <0.0001 for all comparisons). These 4 gene sets showed increased expression with increasing pathological AMR (pAMR) International Society for Heart and Lung Transplantation grade ( P <0.001) and association with donor-specific antibody levels. The unsupervised principal components analysis demonstrated a high proportion of molecularly inactive pAMR1(I+), and there was significant molecular overlap between pAMR1(H + ) 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., (© 2017 American Heart Association, Inc.)

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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

We aimed to assess if the outcome of primary prevention implantable cardioverter defibrillators (ICDs) without cardiac resynchronization therapy is dependent on New York Heart Association (NYHA) class. Among the participants of Défibrillateur Automatique Implantable-Prévention Primaire (DAI-PP; NCT01992458) multicenter cohort study, 155 patients in NYHA class I, 504 in NYHA class II, and 188 in NYHA class III had a QRS width <120 ms and were implanted with an ICD without cardiac resynchronization therapy and, thus, were eligible for the purpose of this analysis. Total and specific mortalities and the incidence of appropriate therapies were assessed for every NYHA. During 2,606 patient-years (3.1 ± 2.1 years), 104 (12.3%) subjects died and 188 (22.2%) experienced appropriate therapies. After adjustment, overall mortality increased with NYHA class (adjusted hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.11 to 2.41, p = 0.014), driven by an increase in cardiovascular death. Conversely, incidence of appropriate ICD intervention was comparable among the 3 NYHA groups (NYHA class I 7.43, NYHA class II 7.91, and NYHA class III 12.10 per 100 patient-years; HR 1.19, 95% CI 0.89 to 1.59, p = 0.231). Incidence of ICD-unresponsive sudden death was very low and also comparable (NYHA class I 0.22, NYHA class II 0.36, and NYHA class III 0.83 per 100 patient-years (HR 6.34, 95% CI 0.32 to 124.49, p = 0.224). No significant differences were observed in the other specific modes of death. In conclusion, although patients in NYHA class III have higher overall mortality, they experience a comparable incidence of appropriate ICD therapies. The low incidence of ICD-unresponsive sudden death in all assessed NYHA classes also supports the efficacy of ICDs, irrespective of NYHA class., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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 < 0.0001, respectively). Antibody-mediated injury was observed in 62.1% of failing allografts with pure coronary arteriosclerosis and mixed (arteriosclerosis and atherosclerosis) pattern, while it was not observed in patients with pure coronary atherosclerosis (p = 0.0076). We demonstrate that antibody-mediated rejection is operating in a substantial fraction of failing heart allografts and is associated with severe coronary arteriosclerosis. Unrecognized subclinical antibody-mediated rejection episodes may be observed years before allograft failure., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Anti-HLA donor-specific antibodies (DSAs) cause acute and chronic antibody-mediated rejection (AMR). However, the clinical relevance of anti-HLA-C antibodies remains unclear. We evaluated the clinical relevance of the presence of anti-HLA-C DSA at day 0 in renal transplant recipients. In this retrospective, case-controlled study, 608 patients who underwent kidney transplantation between August 2008 and March 2012 were screened for the presence of isolated anti-HLA-C DSA at day 0. A total of 22 renal transplant recipients were selected and followed for a period of 1 year. AMR was classified according to the Banff classification. The 22 patients were compared with 88 immunized patients. Acute AMR was diagnosed in six patients (27.3%). The median level of DSA at day 0 was 1179 (530-17,941). The mean fluorescence intensity in the anti-C group was 4966 (978-17,941) in the AMR group and 981 (530-8012) in the group of patients without AMR. Acute AMR was diagnosed less frequently in the 88 immunized individuals (9.1%) than in the DSA anti-C group (p = 0.033). The level of DSA at day 0 was predictive for AMR (p = 0.017). Patients with a high level of pretransplant anti-HLA-C DSAs are likely to develop acute AMR during the first year after transplantation., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The association of acute chest pain, elevation of the cardiac enzymes and biological markers of inflammation suggests the diagnosis of myocarditis. The aim of the present study is to evaluate the diagnostic value of the multidetectors cardiac tomodensitometry (MDCT) for the confirmation of this diagnosis., Patients and Methods: From October 2005 to April 2011, 39 patients aged 15.4 to 75.7years (mean 43.3±15.1) underwent a MDCT for suspected acute myocarditis (chest pain, elevation of troponin I, systemic inflammation). The electrocardiogram highlighted repolarization disorders in 27 (69%) patients (negative T waves, elevation of ST segment). The MDCT consisted in a first acquisition phase (imaging of coronary arteries) followed 7minutes later by a late acquisition, with thicker slices (imaging of the myocardium). When the MDCT was performed after a coronary angiography, only the late acquisition was performed. Sixteen patients then underwent a cardiac MRI., Results: No significant coronary stenoses were found in all patients. The MDCT showed homogeneous myocardial enhancement on the early acquisition. A subepicardial late enhancement was found in 30 (76.9%) patients. The subepicardial enhancement was mainly found in the lateral myocardium. In patients who underwent cardiac MRI and MDCT (n=16), there was a good correlation between the enhanced segments. MDCT found differential diagnosis in 11 patients (myocardial infarction, Tako-Tsubo)., Conclusion: The ECG-gated MDCT is a non-invasive and reliable diagnostic tool in patient with suspected myocarditis. It allows at the same time to rule out a significant coronary disease, when no coronary angiography was performed, and to show subepicardial enhancement confirming the diagnosis of myocarditis. While cardiac MRI remains the gold standard, MDCT could prove useful when there is no access to or contraindication for an MRI, studying both the coronary arteries and the myocardium., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)