Cardiogenic Shock in Idiopathic Dilated Cardiomyopathy Patients: Red Flag for Myocardial Decline.

Idiopathic dilated cardiomyopathy (IDCM) is one of the most common forms of nonischemic cardiomyopathy worldwide, possibly leading to cardiogenic shock (CS). Despite this heavy burden, the outcomes of CS in IDCM are poorly reported. Based on a large registry of unselected CS, our aim was to shed light on the 1-year outcomes after CS in patients with and without IDCM. FRENSHOCK was a prospective registry including 772 patients with CS from 49 centers. The 1-year outcomes (rehospitalizations, mortality, heart transplantation [HTx], ventricular assist devices [VAD]) were analyzed and adjusted on independent predictive factors. Within 772 CS included, 78 occurred in IDCM (10.1%). Patients with IDCM had more frequent history of chronic kidney failure and implantable cardioverter-defibrillator implantation. No difference was found in 1-month all-cause mortality between groups (28.2 vs 25.8%for IDCM and others, respectively; adjusted hazard ratio 1.14 [0.73 to 1.77], p = 0.57). Patients without IDCM were more frequently treated with noninvasive ventilation and intra-aortic balloon pump. At 1 year, IDCM led to higher rates of death or cardiovascular rehospitalizations (adjusted odds ratio 4.77 [95% confidence interval 1.13 to 20.1], p = 0.03) and higher rates of HTx or VAD for patients aged <65 years (adjusted odds ratio 2.68 [1.21 to 5.91], p = 0.02). In conclusion, CS in IDCM is a very common scenario and is associated with a higher rate of 1-year death or cardiovascular rehospitalizations and a more frequent recourse to HTx or VAD for patients aged <65 years, encouraging the consideration of it as a red flag for myocardial decline and urging for a closer follow-up and earlier evaluation for advanced heart failure therapies.

Myocardial Revascularization Strategies in ST Elevation Myocardial Infarction Without Urgent Revascularization: Insight From a Nationwide Study.

OBJECTIVE: To analyze the outcomes of patients presenting with ST-segment elevation myocardial infarction (STEMI) without early (<48 hours) revascularization, according to percutaneous versus surgical revascularization. PATIENTS AND METHODS: Based on the French administrative hospital discharge database, the study collected information for all consecutive patients seen for a STEMI in France between January 1, 2010, to June 31, 2019, who underwent either a first percutaneous coronary intervention (PCI) or a first coronary artery bypass graft between 48 hours and 90 days after the index hospitalization. Propensity score matching was used for the analysis of outcomes. RESULTS: Of 71,365 patients with STEMI in the analysis, 59,340 patients underwent PCI and 12,025 patients underwent coronary artery bypass graft. In a matched analysis of 12,012 patients by arm, surgical revascularization was associated with lower rates of all cause (5.1% vs 7.1%; hazard ratio [HR], 0.70; 95% CI, 0.66 to 0.75) and cardiovascular (2.6% vs 3.1%; HR, 0.83; 95% CI, 0.76 to 0.91) death. Rehospitalization for heart failure was less often reported after surgery (5.5% vs 7.5%; HR, 0.76; 95% CI, 0.71 to 0.81) whereas stroke incidence was not statistically different between the two arms (2.1% vs 2.3%; HR, 0.90; 95% CI, 0.80 to 1.00). Major bleeding was less often reported in the PCI arm (4.6% vs 6.1%; HR, 1.31; 95% CI, 1.22 to 1.41). CONCLUSION: In patients with STEMI who did not undergo urgent revascularization (ie, within 48 hours after presentation), surgical revascularization was associated with better outcomes and should be individually considered as an alternative to PCI.

Low-dose corticosteroid therapy for cardiogenic shock in adults (COCCA): study protocol for a randomized controlled trial.

BACKGROUND: Cardiogenic shock (CS) is a life-threatening condition characterized by circulatory insufficiency caused by an acute dysfunction of the heart pump. The pathophysiological approach to CS has recently been enriched by the tissue consequences of low flow, including inflammation, endothelial dysfunction, and alteration of the hypothalamic-pituitary-adrenal axis. The aim of the present trial is to evaluate the impact of early low-dose corticosteroid therapy on shock reversal in adults with CS. METHOD/DESIGN: This is a multicentered randomized, double-blind, placebo-controlled trial with two parallel arms in adult patients with CS recruited from medical, cardiac, and polyvalent intensive care units (ICU) in France. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 380 patients (190 per group). For the treatment group, hydrocortisone (50 mg intravenous bolus every 6 h) and fludrocortisone (50 µg once a day enterally) will be administered for 7 days or until discharge from the ICU. The primary endpoint is catecholamine-free days at day 7. Secondary endpoints include morbidity and all-cause mortality at 28 and 90 days post-randomization. Pre-defined subgroups analyses are planned, including: postcardiotomy, myocardial infarction, etomidate use, vasopressor use, and adrenal profiles according the short corticotropin stimulation test. Each patient will be followed for 90 days. All analyses will be conducted on an intention-to-treat basis. DISCUSSION: This trial will provide valuable evidence about the effectiveness of low dose of corticosteroid therapy for CS. If effective, this therapy might improve outcome and become a therapeutic adjunct for patients with CS. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03773822 . Registered on 12 December 2018.

Outcome of Temporary Circulatory Support As a Bridge-to-Left Ventricular Assist Device Strategy in Cardiogenic Shock Patients.

OBJECTIVES: Temporary circulatory support (TCS) as a bridge-to-left ventricular assist device (BTL) in cardiogenic shock patients has been increasing, but limited data exists on this BTL strategy. We aimed at analyzing the outcome of BTL patients in a population of cardiogenic shock patients compared with those without TCS at the time of the left ventricular assist device (LVAD) surgery and identify predictors of postoperative mortality in this specific population. DESIGN: A multicenter retrospective observational study conducted in 19 centers from 2006 to 2016. SETTING: Nineteen French centers. PATIENTS: A total of 329 cardiogenic shock patients at the time of LVAD implantation were analyzed. Patients were divided in three groups: those under TCS at the time of LVAD implantation (n = 173), those with TCS removal before LVAD surgery (n = 24), and those who did not undergo a bridging strategy (n = 152). Primary endpoint was 30-day mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the BTL group, 68 (39.3%), 18 (10.4%), and 15 (8.7%) patients were under venoarterial extracorporeal membrane oxygenation, Impella, and IABP support alone, and 72 patients (20.6%) were under multiple TCS support. BTL patients presented similar 30 days survival compared with the TCS removal and non-BTL groups. However, BTL group had a significantly longer ICU duration stay, with two-fold duration of mechanical ventilation time, but the three groups experienced similar postoperative complications. Multivariate analysis identified three independent predictors of mortality in the BTL group: combined surgery with LVAD, body mass index (BMI), and heart failure (HF) duration. BTL strategy was not an independent predictor of mortality in cardiogenic shock patients who underwent LVAD. CONCLUSIONS: BTL strategy is not associated with a lower survival among cardiogenic shock patients with LVAD implantation. Predictors of mortality are combined surgery with LVAD, higher BMI, and HF duration.

Acute myocarditis with autoimmune features: one-year follow-up with CMR.

In this prospective study on patients with acute myocarditis (AM), we aimed to describe the new concept of AMAF (AM with autoimmune features) similar to the previously described interstitial pneumonia with autoimmune features (IPAF). IPAF has recently emerged as a new entity, and IPAF patients appear to have fewer episodes of exacerbation and better survival than patients with idiopathic pulmonary fibrosis. Consecutive patients with infarct-like CMR-confirmed AM were classified AMAF if their serologic status measured from blood sampled at presentation was positive (antinuclear antibodies (ANA) ≥ 1:320), but without meeting established classification criteria for connective tissue disease (CTD). The myocardial tissue abnormalities and their progression were assessed on cardiac magnetic resonance (CMR) within 7 days following symptom onset and at 1 year according to their seropositivity. Among the 64 AM patients included, seven presented AMAF (11%). At baseline CMR, patients with AMAF had half as much late gadolinium enhancement (LGE) as seronegative AM patients (4.41% (1.47-4.41) of myocardial volume versus 8.82% (5.88-14.71), p = 0.01, respectively). At 1-year of follow-up, persistent myocardial scarring was less frequent in AMAF patients (n = 2 (28.6%) than seronegative AM patients (n = 38 (66.7%) (p = 0.021). AMAF, diagnosed as seropositive AM without a specific autoimmune disease, is not rare and is associated with less extensive LGE in the acute phase. In addition, AMAF patients had more favorable outcomes on 12-month CMR. Prospective studies are needed to address the clinical significance of this new concept and its long-term cardiovascular impact.

Characteristics and outcome of ambulatory heart failure patients receiving a left ventricular assist device.

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.

Outcomes in patients with acute myocardial infarction and history of illicit drug use: a French nationwide analysis.

AIMS: Several reports suggest that illicit drug use may be a major cause of acute myocardial infarction (AMI) independently of smoking habits and associated with a poorer prognosis. The aim of our study was to evaluate the impact of illicit drug use on (i) the risk of AMI and (ii) its prognosis. METHODS AND RESULTS: This French longitudinal cohort study was based on the administrative hospital-discharge database from the entire population. First, we collected data for all patients admitted in hospital in 2013 with at least 5 years of follow-up to identify potential predictors of AMI. In a second phase, we collected data for all patients admitted with AMI from January 2010 to December 2018. We identified patients with a history of illicit drug use (cannabis, cocaine, or opioid). These patients were matched with patients without illicit drug use to assess their prognosis. In 2013, 3 381 472 patients were hospitalized with a mean follow-up of 4.7 ± 1.8 years. In multivariable analysis, among all drugs under evaluation, only cannabis use was significantly associated with a higher risk of AMI [HR 1.32 (95% CI 1.09-1.59), P = 0.004]. Between January 2010 and December 2018, we then identified 738 899 AMI patients. Among these patients, 3827 (0.5%) had a known history of illicit drug use. These patients were younger, most often male and had less comorbidities. After 1:1 propensity score matching, during a mean follow-up of 1.9 ± 2.3 years, there was no significant difference between patients without illicit drug use and patients with illicit drug use regarding all-cause death, cardiovascular death, stroke, or heart failure. CONCLUSION: In a large and systematic nationwide analysis, cannabis use was an independent risk factor for the incidence of AMI. However, the prognosis of illicit drug users presenting with AMI was similar to patients without illicit drug use.

Risk Scores in ST-Segment Elevation Myocardial Infarction Patients with Refractory Cardiogenic Shock and Veno-Arterial Extracorporeal Membrane Oxygenation.

Although many risk models have been tested in patients implanted by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), few scores assessed patients' prognosis in the setting of ST-segment elevation myocardial infarction (STEMI) with refractory cardiogenic shock. We aimed at assessing the performance of risk scores, notably the prEdictioN of Cardiogenic shock OUtcome foR AMI patients salvaGed by VA-ECMO (ENCOURAGE) score, for predicting mortality in this particular population. This retrospective observational study included patients admitted to Tours University Hospital for STEMI with cardiogenic shock and requiring hemodynamic support by VA-ECMO. Among the fifty-one patients, the 30-day and 6-month survival rates were 63% and 56% respectively. Thirty days after VA-ECMO therapy, probabilities of mortality were 12, 17, 33, 66, 80% according to the ENCOURAGE score classes 0-12, 13-18, 19-22, 23-27, and ≥28, respectively. The ENCOURAGE score (AUC of the Receiving Operating Characteristic curve = 0.83) was significantly better compared to other risk scores. The hazard ratio for survival at 30 days for each point of the ENCOURAGE score was 1.10 (CI 95% (1.06, 1.15); p < 0.001). Decision curve analysis indicated that the ENCOURAGE score had the best clinical usefulness of the tested risk scores and the Hosmer-Lemeshow test suggested an accurate calibration. Our data suggest that the ENCOURAGE score is valid and the most relevant score to predict 30-day mortality after VA-ECMO therapy in STEMI patients with refractory cardiogenic shock. It may help decision-making teams to better select STEMI patients with shock for VA-ECMO therapy.

Comparison of Outcomes and Mortality in Patients Having Left Ventricular Assist Device Implanted Early -vs- Late After Diagnosis of Cardiomyopathy.

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.

Insights for increased risk of failed fibrinolytic therapy and stent thrombosis associated with COVID-19 in ST-segment elevation myocardial infarction patients.

Important health resources are dedicated worldwide to the management of COVID-19. This new disease, due to its large diffusion, may significantly hamper the prognosis of other pathologies, such as ST-segment elevation myocardial infarction (STEMI) because of (a) a possible direct negative impact and (b) shortage of first response medical resources and increased delays to reperfusion. We report the case of a 68-year-old man admitted for anterior STEMI and asymptomatic COVID-19. Due to extended transportation delays to a cathlab, he received intravenous fibrinolytic therapy, which failed. Reperfusion was achieved with rescue coronary angioplasty, but the patient experienced two episodes of acute stent thrombosis at 2- and 36-hr following admission and despite optimal medical therapy. He finally died because of cardiogenic shock. This raises concerns about a possible increase in platelet aggregability associated with COVID-19 leading to an increased risk of stent thrombosis, particularly in the context of STEMI. This pleads for the promotion of primary coronary angioplasty as the first-choice revascularization technique in this population and the use of new generation P2Y12 inhibitors. In addition, the use of GPIIb/IIIa inhibitors may be considered in every STEMI patient with COVID-19 to prevent the risk of acute stent thrombosis.

Septuagenarian population has similar survival and outcomes to younger patients after left ventricular assist device implantation.

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.

Relation of Body Mass Index to Outcomes in Patients With Heart Failure Implanted With Left Ventricular Assist Devices.

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.

Current results of left ventricular assist device therapy in France: the ASSIST-ICD registry.

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?).

Cardiac magnetic resonance for assessment of cardiac involvement in Takotsubo syndrome: Do we still need contrast administration?

BACKGROUND: This study evaluated the ability of T1 and T2 mapping cardiovascular magnetic resonance to assess myocardial involvement in Takotsubo syndrome (TTS). We hypothesized that non-contrast mapping techniques can be accurate and sufficient. METHODS: We prospectively analysed 30 patients with TTS and 34 controls. CMR was performed a mean 5 days after the onset of symptoms and after a mean 3 month follow-up. RESULTS: On admission, compared to controls, TTS patients had significantly higher global T2 values (59 ± 8 ms vs 51 ± 4 ms, p < 0.001), native T1 (1053 ± 75 ms vs 960 ± 61 ms, p < 0.001) and extracellular volume (ECV) fraction (29% ± 5 vs 23% ±3, p < 0.001). The sensitivity and specificity for T2 (cut off: 56 ms) were 62% and 97% respectively; for native T1: (cut off 1011 ms) were 72% and 91% respectively; and for ECV (cut off: 27%) were 72% and 97% respectively. Combining T2 and native T1 provided the best sensitivity (91.7%) with a good specificity (88.2%). No patients had late gadolinium enhancement. Segmental analysis showed that T2, native T1 and ECV values were significantly higher in regions with wall motion abnormalities (WMA) compared to normokinetic segments (62 ± 9 ms vs 55 ± 5 ms, p < 0.001; 1060 ± 65 ms vs 1025 ± 56 ms, p = 0.02; and 34% ± 5 vs 29% ± 1, p = 0.02). At follow up, native T1 and ECV values did not normalized. CONCLUSION: In TTS patients, a non-contrast mapping technique provides a high diagnostic accuracy allowing identification of acute and persistent myocardial injury. Segmental analysis showed that myocardial injury is preferably detected in segments with WMA.

Outcomes of Left Ventricular Assist Device Implantation in Patients With Uncommon Etiology Cardiomyopathy.

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 co-morbidities. 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.

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

Sterile inflammation is a key determinant of myocardial reperfusion injuries. It participates in infarct size determination in acute myocardial infarction and graft rejection following heart transplantation. We previously showed that P2Y11 exerted an immunosuppressive role in human dendritic cells, modulated cardiofibroblasts' response to ischemia/reperfusion in vitro and delayed graft rejection in an allogeneic heterotopic heart transplantation model. We sought to investigate a possible role of P2Y11 in the cellular response of cardiomyocytes to ischemia/reperfusion. We subjected human AC16 cardiomyocytes to 5 h hypoxia/1 h reoxygenation (H/R). P2Y11R (P2Y11 receptor) selective agonist NF546 and/or antagonist NF340 were added at the onset of reoxygenation. Cellular damages were assessed by LDH release, MTT assay and intracellular ATP level; intracellular signaling pathways were explored. The role of P2Y11R in mitochondria-derived ROS production and mitochondrial respiration was investigated. In vitro H/R injuries were significantly reduced by P2Y11R stimulation at reoxygenation. This protection was suppressed with P2Y11R antagonism. P2Y11R stimulation following H2O2-induced oxidative stress reduced mitochondria-derived ROS production and damages through PKCε signaling pathway activation. Our results suggest a novel protective role of P2Y11 in cardiomyocytes against reperfusion injuries. Pharmacological post-conditioning targeting P2Y11R could therefore contribute to improve myocardial ischemia/reperfusion outcomes in acute myocardial infarction and cardiac transplantation.