Background Bleeding complications are frequent under left ventricular assist device (LVAD) support. LVAD-associated high shear stress induces increased proteolysis of circulating von Willebrand factor (VWF), which may contribute to this high bleeding rate. Objectives To assess if a prophylactic administration of a VWF concentrate could reduce bleeding rate in LVAD patients Methods In this multicenter open-label randomized controlled study, we investigated the efficacy, safety, and pharmacokinetic of a plasma-derived VWF concentrate (WILFACTIN, LFB), administered prophylactically twice-weekly at 50 IU.kg-1 for 3 months after LVAD implantation, compared with standard of care. The efficacy end points were the difference in the incidence rate of any, clinically significant or major bleeding postrandomization. Bleeding and thrombotic events were reviewed at weeks 1 and 2 and then every 2 weeks. The study ended prematurely due to deficient recruitment and drug supply constraints, leading to prioritization of prescriptions for von Willebrand disease patients. We present the available data. Results Twenty-nine adult patients (166 planned) were randomized and analyzed. VWF prophylaxis resulted in a nonsignificant 55% reduction in bleeding incidence rate compared with standard of care (risk ratio, 0.45; 95% CI, 0.18-1.04; P = .06). Accordingly, there was a similar reduction of clinically relevant and major bleeding in VWF arm. Severe adverse events were similar postrandomization between VWF arm and control arm including deaths (2 and 4, respectively) and thrombotic events (2 in each arm). In pharmacokinetic analysis, a rapid degradation of WILFACTIN occurred within 24 hours. Conclusion The lack of observed therapeutic efficacy of VWF prophylaxis in LVAD setting is likely due to a short-lived prohemostatic effect due to rapid degradation of VWF concentrate.

AbstractAimsRight ventricular failure after left ventricular assist device (LVAD) implantation is a major concern that remains challenging to predict. We sought to investigate the relationship between preoperative pulmonary artery pulsatility index (PAPi) and mortality after LVAD implantation.Methods and resultsA retrospective analysis of the ASSIST‐ICD multicentre registry allowed the assessment of PAPi before LVAD according to the formula [(systolic pulmonary artery pressure − diastolic pulmonary artery pressure)/central venous pressure]. The primary endpoint was survival at 3 months, according to the threshold value of PAPi determined by the receiver operating characteristic (ROC) curve. A multivariate analysis including demographic, echographic, haemodynamic, and biological variables was performed to identify predictive factors for 2 year mortality. One hundred seventeen patients were included from 2007 to 2021. The mean age was 58.45 years (±13.16), with 15.4% of women (sex ratio 5.5). A total of 53.4% were implanted as bridge to transplant and 43.1% as destination therapy. Post‐operative right ventricular failure was observed in 57 patients (48.7%), with no significant difference between survivors and non‐survivors at 1 month (odds ratio 1.59, P = 0.30). The median PAPi for the whole study population was 2.83 [interquartile range 1.63–4.69]. The threshold value of PAPi determined by the ROC curve was 2.84. Patients with PAPi ≥ 2.84 had a higher survival rate at 3 months [PAPi < 2.84: 58.1% [46.3–72.8%] vs. PAPi ≥ 2.84: 89.1% [81.1–97.7%], hazard ratio (HR) 0.08 [0.02–0.28], P < 0.01], with no significant difference after 3 months (HR 0.67 [0.17–2.67], P = 0.57). Other predictors of 2 year mortality were systemic hypertension (HR 4.22 [1.49–11.97], P < 0.01) and diabetes mellitus (HR 4.90 [1.83–13.14], P < 0.01). LVAD implantation as bridge to transplant (HR 0.18 [0.04–0.74], P = 0.02) and heart transplantation (HR 0.02 [0.00–0.18], P < 0.01) were associated with a higher survival rate at 2 years.ConclusionsPreoperative PAPi < 2.84 was associated with a higher risk of early mortality after LVAD implantation without impacting 2 year outcomes among survivors.

Acute type A aortic dissection is one of the most hazardous acute vascular pathology. To investigate trends in the management of acute type A aortic dissections on the last 15 years. All consecutive patients who were operated on for an acute type A aortic dissection at the CHU of Toulouse, France, between 2005 and 2019 were retrospectively included. We compared demographics, diagnostic methods and surgical techniques between 3 periods: 2005–2009, 2010–2014 and 2015–2019 (Table 1). A total of 507 patients were included, mean age was 63 ± 12 years, 354 (70%) were male and 299 (59%) had hypertension. Demographics were similar across periods. About clinical presentation, the proportion of patients admitted to the operating room with cardiac arrest has increased between the 3 periods (12% vs 5% vs7%; P < 0.01). Regarding diagnostic, CT was the cornerstone (90%) and the use of TEE has increased (26% vs 10% vs 10%, P < 0.01). Regarding surgical management, we observed a decrease of the use of mechanical prosthesis (6% vs 17% vs 12%; P < 0.01), an increase of the use of hybrid prosthesis (10% vs 2% vs 0%; P < 0.01), of valve sparing (6% vs 0% vs 0%; P < 0.01) and of Bentall (29% vs 25% vs 13%; P < 0.01) (Fig. 1). Over a 15-years period, the demographics of patients operated on for type A aortic dissection has not significantly changed. However, there is a trend towards the management of patients in a more life-threatening condition. Most of the shifts relate to surgical techniques, with a more proactive approach to the treatment of associated aortic regurgitation.

AIM:Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF.METHODS AND RESULTS:The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA-R) will collect data from ACHD evaluated or listed for heart or heart-combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989-2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All-cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment.CONCLUSION:The ARTORIA-R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.

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.

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 impact of uncommon etiology cardiomyopathies on Left-ventricular assist device (LVAD)-recipient outcomes is not very well known. This study aimed to characterize patients with uncommon cardiomyopathy etiologies and examine the outcomes between uncommon and ischemic/idiopathic dilated cardiomyopathy. This observational study was conducted in 19 centers between 2006 and 2016. Baseline characteristics and outcomes of patients with uncommon etiology were compared to patients with idiopathic dilated/ischemic cardiomyopathies. Among 652 LVAD-recipients included, a total of 590 (90.5%) patients were classified as ischemic/idiopathic and 62 (9.5%) patients were classified in the "uncommon etiologies" group. Main uncommon etiologies were: hypertrophic (n = 12 (19%)); cancer therapeutics-related cardiac dysfunction (CTRCD) (n = 12(19% )); myocarditis (n = 11(18%)); valvulopathy (n = 9(15 %)) and others (n = 18(29%)). Patients with uncommon etiologies were significantly younger with more female and presented less comorbidities. Additionally, patients with uncommon cardiomyopathies were less implanted as destination therapy compared with ischemic/idiopathic group (29% vs 38.8%). During a follow-up period of 9.1 months, both groups experienced similar survival. However, subgroup of hypertrophic/valvular cardiomyopathies and CTRCD had significantly higher mortality compared to the ischemic/idiopathic or myocarditis/others cardiomyopathies. Conversely, patients with myocarditis/others etiologies experienced a better survival. Indeed, the 12-months survival in the myocarditis/others; ischemic/idiopathic and hypertrophic/CTRCD/valvulopathy group were 77%; 65%, and 46% respectively. In conclusion, LVAD-recipients with hypertrophic cardiomyopathy, valvular heart disease and CTRCD experienced the higher mortality rate. (C) 2020 Elsevier Inc. All rights reserved.

Objective: Residual False Lumen (FL) patency after chronic type A or type B Aortic Dissection (AD) treatment is an independent factor of poor longterm outcome. The aim of this study was to evaluate ancillary endovascular procedures in progressive AD, to improve false lumen thrombosis and aortic remodeling. Methods: Between August 2005 and December 2017, 59 ancillary endovascular procedures were performed in 35 consecutive patients for aneurysmal expansion, aortic rupture or malperfusion syndrome. Sixteen patients (45.7%) presented an initial type A AD treated by open aortic surgery, and 19 (54.3%) presented a type B AD, previously treated by TEVAR. Aortic remodeling was evaluated on the preprocedural and on the most recent computed tomography angiography followup for each patient. Results: At a median follow-up time of 60.7 months [44.4-76.8], 59 ancillary endovascular procedures were performed. At the end of the follow-up, positive remodeling was obtained in 85.7% of cases with a complete false lumen thrombosis in 9 patients (25.7%), and a diameter reduction or stability (<5 mm increase) in 21 patients (60.0%). The mean total false lumen thrombosis score before the first ancillary procedure was 0.97 (± 0.90) vs. 2.54 (± 0.98) at the end of the follow-up, p<0.0001. One patient died of a retrograde dissection, 2 days after a proximal aortic stent graft extension. Conclusion: Ancillary endovascular procedures are effective and safe to promote aortic remodeling in progressive chronic AD.

Background: The soluble form of the IL-33 receptor (sST2) and Galectin-3 (Gal-3) are fibrosis biomarkers with prognostic value in heart failure (HF). We investigated the prognostic capacity of sST2 when combined with Gal-3, and determined if the prognostic utility of sST2 is affected by mineralocorticoid receptor antagonist (MRA) therapy. Methods: sST-2 and Gal-3 were measured in 101 stable chronic HF (CHF) patients receiving MRA therapy and compared to 97 BNP and cardiovascular risk factor matched patients not treated with MRA. sST2 and Gal-3 levels were measured to determine the relationship with all-cause mortality at 6-year follow-up. Results: ROC curve cut-off points were defined as sST2 = 36.3 ng/mL, Gal-3 = 17.8 ng/mL, and BNP = 500 pg/mL, and had 6-year mortality hazard ratios (HR) of 7.3, 6.6 and 5.4, respectively. The combination of an elevated sST2 and Gal-3 had a HR = 4.4 [95% CI 1.9-8.9]. Combining sST2 and Gal-3 to a clinical model relevant for CHF prognosis allowed a significant reclassification of 1-year adverse outcome risk, even when BNP was included. Finally, prognostic prediction by sST2 was unaffected by MRA treatment. Conclusion: Simultaneous sST2 and Gal-3 elevation is associated with poorer prognosis compared to either alone, regardless of BNP levels, and the prognostic capacity of sST2 is independent of MRA therapy.

HomeCirculationVol. 141, No. 11Suicide Attempts Among LVAD Recipients Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplementary MaterialsFree AccessLetterPDF/EPUBSuicide Attempts Among LVAD RecipientsReal-Life Data From the ASSIST-ICD Study Marion Charton, MD, Erwan Flécher, MD, PhD, Christophe Leclercq, MD, PhD, Clément Delmas, MD, Camille Dambrin, MD, PhD, Céline Goeminne, MD, André Vincentelli, MD, PhD, Magali Michel, MD, Laurence Lehelias, MD, Constance Verdonk, MD, Marylou Para, MD, Matteo Pozzi, MD, Jean-François Obadia, MD, PhD, Aude Boignard, MD, Olivier Chavanon, MD, PhD, Laurent Barandon, MD, PhD, Karine Nubret, MD, Michel Kindo, MD, PhD, Tam Hoang Minh, MD, Philippe Gaudard, MD, Edeline Pelcé, MD, Vlad Gariboldi, MD, PhD, Pierre-Yves Litzler, MD, PhD, Frédéric Anselme, MD, Gerard Babatasi, MD, PhD, Annette Belin, MD, Fabien Garnier, MD, Marie Bielefeld, MD, David Hamon, MD, Nicolas Lellouche, MD, PhD, Thierry Bourguignon, MD, Thibaud Genet, MD, Romain Eschalier, MD, PhD, Nicolas D'Ostrevy, MD, Marie-Cécile Bories, MD, Jérôme Jouan, MD, Fabrice Vanhuyse, MD, Hugues Blangy, MD, Julie Doucerain, MD, Raphael P. Martins, MD, PhD and Vincent Galand, MD Marion ChartonMarion Charton INSERM, LTSI-UMR 1099, Univ Rennes (M.C., E.F., C.L., R.P.M., V. Galand), CHU Rennes, France. , Erwan FlécherErwan Flécher INSERM, LTSI-UMR 1099, Univ Rennes (M.C., E.F., C.L., R.P.M., V. Galand), CHU Rennes, France. Department of Cardiac Surgery and Heart Transplantation Unit (E.F.), CHU Rennes, France. , Christophe LeclercqChristophe Leclercq INSERM, LTSI-UMR 1099, Univ Rennes (M.C., E.F., C.L., R.P.M., V. Galand), CHU Rennes, France. , Clément DelmasClément Delmas Centre Hospitalier Universitaire de Toulouse, France (C. Delmas, C. Dambrin). , Camille DambrinCamille Dambrin Centre Hospitalier Universitaire de Toulouse, France (C. Delmas, C. Dambrin). , Céline GoeminneCéline Goeminne Department of Cardiac Surgery, Cardiology, Cardiac Intensive Care Unit, Institut Coeur-Poumons, CHU Lille, France (C.G., A.V.). , André VincentelliAndré Vincentelli Department of Cardiac Surgery, Cardiology, Cardiac Intensive Care Unit, Institut Coeur-Poumons, CHU Lille, France (C.G., A.V.). , Magali MichelMagali Michel Department of Cardiology and Heart Transplantation Unit, CHU Nantes, France (M.M., L.L.). , Laurence LeheliasLaurence Lehelias Department of Cardiology and Heart Transplantation Unit, CHU Nantes, France (M.M., L.L.). , Constance VerdonkConstance Verdonk Department of Cardiology and Cardiac Surgery, Bichat-Hospital, Paris, France (C.V., M. Para). , Marylou ParaMarylou Para Department of Cardiology and Cardiac Surgery, Bichat-Hospital, Paris, France (C.V., M. Para). , Matteo PozziMatteo Pozzi Department of Cardiac Surgery, Louis Pradel Cardiologic Hospital, Lyon, France (M. Pozzi, J.-F.O.). , Jean-François ObadiaJean-François Obadia Department of Cardiac Surgery, Louis Pradel Cardiologic Hospital, Lyon, France (M. Pozzi, J.-F.O.). , Aude BoignardAude Boignard Department of Cardiology and Cardiovascular Surgery, CHU Michallon, Grenoble, France (A.B., O.C.). , Olivier ChavanonOlivier Chavanon Department of Cardiology and Cardiovascular Surgery, CHU Michallon, Grenoble, France (A.B., O.C.). , Laurent BarandonLaurent Barandon Hôpital Cardiologique du Haut-Lévêque, Université Bordeaux II, France (L.B., K.N.). , Karine NubretKarine Nubret Hôpital Cardiologique du Haut-Lévêque, Université Bordeaux II, France (L.B., K.N.). , Michel KindoMichel Kindo Département de Chirurgie Cardiovasculaire, Hôpitaux Universitaires de Strasbourg, France (M.K., T.H.M.). , Tam Hoang MinhTam Hoang Minh Département de Chirurgie Cardiovasculaire, Hôpitaux Universitaires de Strasbourg, France (M.K., T.H.M.). , Philippe GaudardPhilippe Gaudard PhyMedExp, Université de Montpellier, INSERM, CNRS, Arnaud De Villeneuve Department of Anesthesiology and Critical Care Medicine, CHU Montpellier, France (P.G.). , Edeline PelcéEdeline Pelcé Department of Cardiac Surgery, La Timone Hospital, Marseille, France (E.P., V. Gariboldi). , Vlad GariboldiVlad Gariboldi Department of Cardiac Surgery, La Timone Hospital, Marseille, France (E.P., V. Gariboldi). , Pierre-Yves LitzlerPierre-Yves Litzler Department of Cardiology and Cardiovascular Surgery, Hospital Charles Nicolle, Rouen, France (P.-Y.L., F.A.). , Frédéric AnselmeFrédéric Anselme Department of Cardiology and Cardiovascular Surgery, Hospital Charles Nicolle, Rouen, France (P.-Y.L., F.A.). , Gerard BabatasiGerard Babatasi Department of Cardiology and Cardiac Surgery, University of Caen and University Hospital of Caen, France (G.B., A.B.). , Annette BelinAnnette Belin Department of Cardiology and Cardiac Surgery, University of Caen and University Hospital of Caen, France (G.B., A.B.). , Fabien GarnierFabien Garnier Department of Cardiology and Cardiac Surgery, University Hospital, Dijon, France (F.G., M.B.). , Marie BielefeldMarie Bielefeld Department of Cardiology and Cardiac Surgery, University Hospital, Dijon, France (F.G., M.B.). , David HamonDavid Hamon Department of Cardiology and Cardiac Surgery, AP-HP CHU Henri Mondor, Créteil, France (D.H., N.L.). , Nicolas LelloucheNicolas Lellouche Department of Cardiology and Cardiac Surgery, AP-HP CHU Henri Mondor, Créteil, France (D.H., N.L.). , Thierry BourguignonThierry Bourguignon Department of Cardiology and Cardiac Surgery, Tours University Hospital, France (T.B., T.G.). , Thibaud GenetThibaud Genet Department of Cardiology and Cardiac Surgery, Tours University Hospital, France (T.B., T.G.). , Romain EschalierRomain Eschalier CHU Clermont-Ferrand, Cardiology Department, Clermont-Ferrand, France (R.E., N.D.). , Nicolas D'OstrevyNicolas D'Ostrevy CHU Clermont-Ferrand, Cardiology Department, Clermont-Ferrand, France (R.E., N.D.). , Marie-Cécile BoriesMarie-Cécile Bories European Georges Pompidou Hospital, Cardiology Department, Paris, France (M.-C.B., J.J.). , Jérôme JouanJérôme Jouan European Georges Pompidou Hospital, Cardiology Department, Paris, France (M.-C.B., J.J.). , Fabrice VanhuyseFabrice Vanhuyse Department of Cardiology and Cardiac Surgery, CHU de Nancy, Hopital de Brabois, Nancy, France (F.V., H.B.). , Hugues BlangyHugues Blangy Department of Cardiology and Cardiac Surgery, CHU de Nancy, Hopital de Brabois, Nancy, France (F.V., H.B.). , Julie DoucerainJulie Doucerain Service de Psychiatrie (J.D.), CHU Rennes, France. , Raphael P. MartinsRaphael P. Martins INSERM, LTSI-UMR 1099, Univ Rennes (M.C., E.F., C.L., R.P.M., V. Galand), CHU Rennes, France. and Vincent GalandVincent Galand Vincent Galand, MD, CHU Rennes, Rue Henri Le Guilloux, F-35000 Rennes, France. Email E-mail Address: [email protected] INSERM, LTSI-UMR 1099, Univ Rennes (M.C., E.F., C.L., R.P.M., V. Galand), CHU Rennes, France. Originally published10 Mar 2020https://doi.org/10.1161/CIRCULATIONAHA.119.041910Circulation. 2020;141:934–936Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: March 10, 2020: Ahead of Print Left ventricular assist device (LVAD) implantation is an alternative therapy for end-stage heart failure. Numerous complications are associated with LVADs, including psychiatric disorders such as anxiety and depression. Data regarding the suicide risk in this population are lacking. We aimed at describing the incidence of suicide in LVAD recipients included in the multicenter ASSIST-ICD observational study (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 (https://www.clinicaltrials.gov; unique identifier: NCT02873169) is a study of LVAD implanted in 19 French centers. Detailed methods have been published.1 Among the 659 LVAD recipients included, 494 (87% men; mean age, 58.9 years [range, 50.3 to 65.8]) were discharged from the hospital and included in this study. History of suicide attempts was reviewed. Clinical data, psychiatric history, and characteristics of suicide or suicide attempts were collected for each patient. The study was approved by an institutional review committee, and the participants gave informed consent.Among the 494 patients, 10 (2.0%) attempted or completed suicide over 18.8 months of follow-up. Eight completed suicide, either by unplugging or sectioning their LVAD cable or drug intoxication; 1 attempted suicide by drug intoxication; and 1 attempted suicide by driveline section. Their characteristics are summarized in the Table. Nine were men, and 2 had a history of a psychiatric disorder. Of note, 8 of 10 (80%) patients were implanted as destination therapy compared with 162 of 484 (33.5%) patients without suicide (P=0.006). Of the 10 patients who attempted or completed suicide, 4 did not have a psychiatric evaluation before LVAD surgery. The median duration of hospital stay after LVAD surgery was 46.5 days (range, 36.0 to 70.0) and suicide attempt occurred on average 12.5 months after the LVAD implantation. Six patients experienced ≤1 hospitalization after initial hospital discharge. A majority of patients (8 of 10) expressed psychiatric symptoms, such as sadness, solitude, or hopelessness. Of 10 patients who attempted or completed suicide, 2 (20%) were followed in a center with an LVAD coordinator compared with 293 of 484 (60.5%) patients without suicide attempt (P=0.02).In France, the suicide attempt rate is ~0.03% per year (200,000 events/year). This frequency increases among patients with chronic diseases such as chronic heart failure (0.06%/year). In our series, the incidence of suicide in LVAD recipients (2% after 18.8 months of follow-up) appears even higher than in those with other chronic diseases. In the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support), psychiatric episodes were estimated around 1%, but the prevalence of suicide was not specified.2The reasons for the apparently increased incidence of attempted or completed suicide in LVAD recipients are speculative. Our data identified 2 variables that were associated with attempted or completed suicide: implantation for destination therapy and follow-up at a center without an LVAD coordinator. If confirmed by others, the latter is a potentially modifiable practice that could be tested as a means to lower the frequency of suicide. There is plausibility to this finding given that LVAD coordinators are in a unique position, serving as a link between patients' families and medical teams, and could identify early symptoms of psychiatric disorders. Similarly, staff at cardiac rehabilitation centers may have this opportunity, although our data did not address this possibility. We found a high frequency of psychiatric symptoms (80%) among those who attempted or completed suicide, highlighting the role for psychiatrists as part of a multidisciplinary LVAD team.A number of potential factors, such as alteration of body image, lack of return to full-time employment, feeling burdensome to caregivers, or increased dependence on the medical team, could contribute to the development of psychiatric symptoms in LVAD recipients. Ensuring that patients have rigorous motivation for the treatment, social support, and extensive preoperative education about life after LVAD implantation may mitigate the development of such symptoms. Assessing patients' satisfaction or decision regret after LVAD implantation could identify those requiring psychological support and detect emerging signs of psychological distress, especially in patients implanted as destination therapy.3In conclusion, we found a 2.0% risk of attempted or completed suicide in LVAD recipients, which is higher than in the general population or those with other chronic diseases in France. These data emphasize the need to develop strategies to minimize the risk of this event in LVAD recipients, especially among those implanted as destination therapy.Table. Patient Characteristics and Follow-UpPatient No.SexAge at LVAD Surgery, y/Duration of Heart Failure, yComorbiditiesHistory of Psychiatric DiseaseSocial SituationPsychiatric Evaluation Before LVADINTERMACSLVADDays in Hospital After LVAD, nNew York Heart Association Classification After LVADSix-Meter Walk Test, mCardiac Events/Symptoms After LVADHospitalization After LVAD, nPsychiatric Symptoms ExpressedMethod of Suicide or Attempted SuicideTime From LVAD to Suicide or Attempt, mo1Male71/17DyslipidemiaNoMarried, 2 childrenNo1DT84IVNAAsthenia0Sadness, solitudeDriveline section3.72Male71/<1Active smokingNoWidower, alone on an island, girlfriend far awayYes2DT28INASevere right ventricular heart failure4Aggressive, sadness, far from homeBattery disconnection153Male59/9Arterial vascular disease, active smoking, alcohol abuseNoMarriedYes≥4DT170II415Numerous LVAD infections1NoDriveline section8.34Female49/10Arterial vascular disease, weaned smoking, obesityDepression, suicide attemptMarried, marital disputeYes≥4DT13I450Asymptomatic1Malaise, marital disputeBattery disconnection25.95Male58/18Arterial vascular disease, ischemic stroke, renal insufficiencyNoMarried, children and grandsonNo2DT70INAAsymptomatic0Hopeless, ruined his lifeDriveline section24.56Male70/<1Active smokingNoMarriedNo1DT48III350Bleeding, pulmonary complication0Failure to thriveDrug intoxication1.27Male50/2Active smokingNoDutch living in France for 14 years, divorced, 2 children, financial difficulties, did not speak FrenchYes≥4Bridge to transplant36II435Asthenia1Sadness, solitudeTwo drug intoxications (suicide attempt)10 and 128Male64/8Obesity, chronic obstructive pulmonary diseaseNoMarried, 3 childrenYes≥4DT45III400Aortic insufficiency, bleeding8Strong care opposition, refused psychiatric careDriveline section589Male56/1ObesityStable schizophreniaIn relationshipYes≥4Bridge to transplant61III300Several LVAD infections4NoDriveline section (suicide attempt)4810Male71/1Chronic obstructive pulmonary disease, strokeNoMarried, marital disputeNo2DT41III410Severe chronic obstructive pulmonary disease2Sadness, no support from his wife, belittled by his wifeBattery disconnection10DT indicates destination therapy; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support; LVAD, left ventricular assist device; and NA, not available.AcknowledgmentsEditorial support was provided by Dr William J. Hucker.Sources of FundingThis research was supported by the French Federation of Cardiology.DisclosuresNone.FootnotesThe full author list is available on page 935.https://www.ahajournals.org/journal/circThe data, analytic methods, and study materials are not available to other researchers.Vincent Galand, MD, CHU Rennes, Rue Henri Le Guilloux, F-35000 Rennes, France. Email vincent.[email protected]comReferences1. Galand V, Flécher E, Auffret V, Boulé S, Vincentelli A, Dambrin C, Mondoly P, Sacher F, Nubret K, Kindo M, et al; ASSIST-ICD Investigators. Predictors and clinical impact of late ventricular arrhythmias in patients with continuous-flow left ventricular assist devices.JACC Clin Electrophysiol. 2018; 4:1166–1175. doi: 10.1016/j.jacep.2018.05.006CrossrefMedlineGoogle Scholar2. Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Stevenson LW, Blume ED, Myers SL, Miller MA, Baldwin JT, Young JB. Seventh INTERMACS annual report: 15,000 patients and counting.J Heart Lung Transplant. 2015; 34:1495–1504. doi: 10.1016/j.healun.2015.10.003CrossrefMedlineGoogle Scholar3. Allen LA, McIlvennan CK, Thompson JS, Dunlay SM, LaRue SJ, Lewis EF, Patel CB, Blue L, Fairclough DL, Leister EC, et al. Effectiveness of an intervention supporting shared decision making for destination therapy left ventricular assist device: the DECIDE-LVAD randomized clinical trial.JAMA Intern Med. 2018; 178:520–529. doi: 10.1001/jamainternmed.2017.8713CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Rossi Ferrario S, Panzeri A and Pistono M (2021) Psychological difficulties of LVAD patients and caregivers: A follow up over one year from discharge, Artificial Organs, 10.1111/aor.14071, 46:3, (479-490), Online publication date: 1-Mar-2022. Sladen R, Shulman M, Javaid A, Hodgson C, Myles P, Mcgiffin D, Nakagawa S, Amlani A, Hupf J, Takeda K, Naka Y, Takayama H, Bergin P, Buckland M, Yozefpolskaya M and Colombo P (2022) Postdischarge Functional Capacity, Health-Related Quality of Life, Depression, Anxiety, and Post-traumatic Stress Disorder in Patients Receiving a Long-term Left Ventricular Assist Device, Journal of Cardiac Failure, 10.1016/j.cardfail.2021.07.019, 28:1, (83-92), Online publication date: 1-Jan-2022. Chi J, Chen F, Liu Y and Jin L (2022) Suicide risk in patients with heart failure: A systematic review and meta-analysis, Asian Journal of Psychiatry, 10.1016/j.ajp.2021.102980, 68, (102980), Online publication date: 1-Feb-2022. Jiménez-Blanco Bravo M, Zamorano Gómez J, del Prado Díaz S, Alonso Salinas G, Cameli M, Mapelli M, Mango F, Bernstein B and Vervaat F (2021) A suicide attempt on a left ventricular assist device patient during COVID-19 pandemic: can we only blame the virus? A case report, European Heart Journal - Case Reports, 10.1093/ehjcr/ytab144, 5:5, Online publication date: 3-May-2021. Edwards J, Edelson J, Katcoff H, Mondal A, Lefkowitz D, Reza N, Hanff T, Griffis H, Mazurek J, Wald J, Owens A, Wittlieb-Weber C, Burstein D, Atluri P, O'Connor M, Goldberg L, Zamani P, Groeneveld P, Rossano J, Lin K and Birati E (2021) Mental health disorders and emergency resource use and outcomes in ventricular assist device supported patients, American Heart Journal, 10.1016/j.ahj.2021.05.018, 240, (11-15), Online publication date: 1-Oct-2021. Nakagawa S, Uriel N and Prager K (2020) Should It Be Called "Suicide" or "Withdrawal of LVAD Support"?, Journal of Pain and Symptom Management, 10.1016/j.jpainsymman.2020.08.021, 60:5, (e1-e3), Online publication date: 1-Nov-2020. Mariani S, Napp L and Schmitto J (2020) Mens sana in corpore sano: Challenges beyond LVAD implantation, Artificial Organs, 10.1111/aor.13774, 44:12, (1310-1311), Online publication date: 1-Dec-2020. Galand V, Flécher E, Chabanne C, Lelong B, Goéminne C, Vincentelli A, Delmas C, Dambrin C, Nubret K, Pernot M, Kindo M, Hoang Minh T, Gaudard P, Frapier J, Michel M, Sénage T, Boignard A, Chavanon O, Verdonk C, Para M, Pelcé E, Gariboldi V, Pozzi M, Obadia J, Litlzer P, Anselme F, Babatasi G, Plane A, Garnier F, Bielefeld M, Hamon D, Radu C, Bourguignon T, Genet T, Eschalier R, D'Ostrevy N, Bories M, Marijon E, Vanhuyse F, Blangy H, Leclercq C and Martins R (2020) Septuagenarian population has similar survival and outcomes to younger patients after left ventricular assist device implantation, Archives of Cardiovascular Diseases, 10.1016/j.acvd.2020.05.018, 113:11, (701-709), Online publication date: 1-Nov-2020. Choi J, Peters C and Nickels M (2022) Arranging Inpatient Psychiatric Treatment for a Patient with a Left Ventricular Assist Device, Progress in Transplantation, 10.1177/15269248221107033, (152692482211070) March 17, 2020Vol 141, Issue 11 Advertisement Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.119.041910PMID: 32153210 Originally publishedMarch 10, 2020 KeywordsLVADsuicide attemptPDF download Advertisement SubjectsCardiovascular SurgeryHeart FailureMental Health

Aims This study explored the lateral crest structures of adult cardiomyocytes (CMs) within healthy and diseased cardiac tissue. Methods and results Using high-resolution electron and atomic force microscopy, we performed an exhaustive quantitative analysis of the three-dimensional (3D) structure of the CM lateral surface in different cardiac compartments from various mammalian species (mouse, rat, cow, and human) and determined the technical pitfalls that limit its observation. Although crests were observed in nearly all CMs from all heart compartments in all species, we showed that their heights, dictated by the subsarcolemmal mitochondria number, substantially differ between compartments from one species to another and tightly correlate with the sarcomere length. Differences in crest heights also exist between species; for example, the similar cardiac compartments in cows and humans exhibit higher crests than rodents. Unexpectedly, we found that lateral surface crests establish tight junctional contacts with crests from neighbouring CMs. Consistently, super-resolution SIM or STED-based immunofluorescence imaging of the cardiac tissue revealed intermittent claudin-5-claudin-5 interactions in trans via their extracellular part and crossing the basement membrane. Finally, we found a loss of crest structures and crest-crest contacts in diseased human CMs and in an experimental mouse model of left ventricle barometric overload. Conclusion Overall, these results provide the first evidence for the existence of differential CM surface crests in the cardiac tissue as well as the existence of CM-CM direct physical contacts at their lateral face through crest-crest interactions. We propose a model in which this specific 3D organization of the CM lateral membrane ensures the myofibril/myofiber alignment and the overall cardiac tissue cohesion. A potential role in the control of sarcomere relaxation and of diastolic ventricular dysfunction is also discussed. Whether the loss of CM surface crests constitutes an initial and common event leading to the CM degeneration and the setting of heart failure will need further investigation.

OBJECTIVES:To characterize the clinical presentation and outcomes of invasive mold infections (IMI) in solid organ transplant (SOT) recipients.METHODS:Inclusion of all SOT recipients with IMI diagnosed between 2008 and 2016 at a referral center for SOT. Univariable analyses identified factors associated with death at one year, and logistic regression models retained independent predictors.RESULTS:Of the 1739 patients that received a SOT during this period, 68 developed IMI (invasive aspergillosis [IA] in 58). Cumulative incidence of IMI at 1 year ranged from 1.2% to 18.8% (kidney and heart transplantation, respectively). At baseline, compared with other IMI, the need for vasoactive drugs was more frequent in patients with IA. During follow-up, 35 patients (51%) were admitted to the ICU and required mechanical ventilation (n = 27), vasoactive drugs (n = 31), or renal replacement therapy (n = 31). The need for vasoactive drugs (OR 7.34; P = .003) and a positive direct examination (OR 10.1; P = .004) were independently associated with the risk of death at 1 year in patients with IA (n = 33; 57%) CONCLUSIONS: Characteristics of IMI at presentation varied according to the underlying transplanted organ and the mold species. Following IA, one-year mortality may be predicted by the need for hemodynamic support and initial fungal load.

Background Left ventricular assist device (LVAD)-associated infections may be life-threatening and impact patients' outcome. We aimed to identify the characteristics, risk factors, and prognosis of LVAD-associated infections. Methods Patients included in the ASSIST-ICD study (19 centers) were enrolled. The main outcome was the occurrence of LVAD-associated infection (driveline infection, pocket infection, or pump/cannula infection) during follow-up. Results Of the 652 patients enrolled, 201 (30.1%) presented a total of 248 LVAD infections diagnosed 6.5 months after implantation, including 171 (26.2%), 51 (7.8%), and 26 (4.0%) percutaneous driveline infection, pocket infection, or pump/cannula infection, respectively. Patients with infections were aged 58.7 years, and most receivedHeartMate II (82.1%) orHeartWare (13.4%). Most patients (62%) had implantable cardioverter-defibrillators (ICDs) before LVAD, and 104 (16.0%) had ICD implantation, extraction, or replacement after the LVAD surgery. Main pathogens found among the 248 infections were Staphylococcus aureus (n = 113' 45.4%), Enterobacteriaceae (n = 61; 24.6%), Pseudomonas aeruginosa (n = 34; 13.7%), coagulase-negative staphylococci (n = 13; 5.2%), and Candida species (n = 13; 5.2%). In multivariable analysis, HeartMate II (subhazard ratio, 1.56; 95% CI, 1.03 to 2.36; P =.031) and ICD-related procedures post-LVAD (subhazard ratio, 1.43; 95% CI, 1.03-1.98; P =.031) were significantly associated with LVAD infections. Infections had no detrimental impact on survival. Conclusions Left ventricular assist device-associated infections affect one-third of LVAD recipients, mostly related to skin pathogens and gram-negative bacilli, with increased risk with HeartMate II as compared with HeartWare, and in patients who required ICD-related procedures post-LVAD. This is a plea to better select patients needing ICD implantation/replacement after LVAD implantation.

Background: Insulin-like Growth Factor Binding Protein 2 (IGFBP2) showed greater heart failure (HF) diagnostic accuracy than the "grey zone" B-type natriuretic peptides, and may have prognostic utility as well. Objectives: To determine if IGFBP2 provides independent information on cardiovascular mortality in HF. Methods: A retrospective study of 870 HF patients from 3 independent international cohorts. Presentation IGFBP2 plasma levels were measured by EUSA, and patients were followed from 1 year (Maastricht. Netherlands) to 6 years (Atlanta, GA, USA and Toulouse, France). Multivariate analysis, Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) were performed in the 3 cohorts. The primary outcome was cardiovascular mortality. Results: In multivariate Cox proportional hazards analysis, the highest quartile of IGFBP2 was associated with mortality in the Maastricht cohort (adjusted hazard ratio 1.69 (95% CI 1.18-2.41), p = 0.004) and in the combined Atlanta and Toulouse cohorts (adjusted hazard ratio 2.04 (95%CI, 13-3.3), p = 0.003). Adding IGFBP2 to a clinical model allowed a reclassification of adverse outcome risk in the Maastricht cohort (NRI - 18.7% p = 0.03; IDI - 3.9% p = 0.02) and with the Atlanta/Toulouse patients (NRI of 40.4% p = 0.01, 31,2% p = 0.04, 315% p = 0,02 and IDI of 2,9% p = 0,0005, 3.1% p = 0,0005 and 4,2%, p = 0.0005, fora follow-up of 1, 2 and 3 years, respectively). Conclusion: In 3 international cohorts, IGFBP2 level is a strong prognostic factor for cardiovascular mortality in HF, adding information to natriuretic monitoring and usual clinical markers, that should be further prospectively evaluated for patients optimized care. (C) 2019 Elsevier B.V. All rights reserved.

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 multi-center 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 dur-ing 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.

Aging is a major risk factor in the development of chronic diseases, especially cardiovascular diseases. Age‐related organ dysfunction is strongly associated with the accumulation of senescent cells. Cardiac mesenchymal stromal cells (cMSCs), deemed part of the microenvironment, modulate cardiac homeostasis through their vascular differentiation potential and paracrine activity. Transcriptomic analysis of cMSCs identified age‐dependent biological pathways regulating immune responses and angiogenesis. Aged cMSCs displayed a senescence program characterized by Cdkn2a expression, decreased proliferation and clonogenicity, and acquisition of a senescence‐associated secretory phenotype (SASP). Increased CCR2‐dependent monocyte recruitment by aged cMSCs was associated with increased IL‐1ß production by inflammatory macrophages in the aging heart. In turn, IL‐1ß induced senescence in cMSCs and mimicked age‐related phenotypic changes such as decreased CD90 expression. The CD90+ and CD90‐ cMSC subsets had biased vascular differentiation potentials, and CD90+ cMSCs were more prone to acquire markers of the endothelial lineage with aging. These features were related to the emergence of a new cMSC subset in the aging heart, expressing CD31 and endothelial genes. These results demonstrate that cMSC senescence and SASP production are supported by the installation of an inflammatory amplification loop, which could sustain cMSC senescence and interfere with their vascular differentiation potentials.

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 (C) 2018 by the American College of Cardiology Foundation.

Background: Extracorporeal life support (ECLS) holds the promise of significant improvement of the survival of patient in refractory cardiogenic shock (CS) or cardiac arrest (CA). Nevertheless, it remains to be shown to which extent these highly invasive supportive techniques could improve long-term patient's outcome. Methods: The outcomes of 82 adult ECLS patients at our institution between January 2012 and December 2013 were retrospectively analyzed. Results: Patients were essentially men (64.7%) and are 54 years old. Preexisting ischemic (53.7%) and dilated cardiomyopathy (14.6%) were frequent. ECLS indications were shared equally between CA and CS. ECLS-specific adverse effects as hemorrhage (30%) and infection (50%) were frequent. ECLS was effective for 43 patients (54%) with recovery for 35 (43%), 5 (6%) heart transplant, and 3 (4%) left ventricular assist device support. Mortality rate at 30 days was 59.8%, but long-term and 3-month survival rates were similar of 31.7%. Initial plasma lactate levels 5.3 mmol/L and glomerular filtration rate <43 ml/min/1.73 m(2) were significantly associated with 3-month mortality (risk ratio [RR] 2.58 [1.21u5.48]; P = 0.014; RR 2.10 [1.1u4]; P = 0.024, respectively). Long-term follow-up had shown patients paucisymptomatic (64% New York Heart Association 1u2) and autonomic (activities of daily living [ADL] score 6 1.5). Conclusion: In case of refractory CA or CS, lactates and renal function at ECLS initiation could serve as outcome predictor for risk stratification and ECLS indication.