Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial.

BACKGROUND: Static cold storage (SCS) remains the gold standard for preserving donor hearts before transplantation but is associated with ischaemia, anaerobic metabolism, and organ injuries, leading to patient morbidity and mortality. We aimed to evaluate whether continuous, hypothermic oxygenated machine perfusion (HOPE) of the donor heart is safe and superior compared with SCS. METHODS: We performed a multinational, multicentre, randomised, controlled, open-label clinical trial with a superiority design at 15 transplant centres across eight European countries. Adult candidates for heart transplantation were eligible and randomly assigned in a 1:1 ratio. Donor inclusion criteria were age 18-70 years with no previous sternotomy and donation after brain death. In the treatment group, the preservation protocol involved the use of a portable machine perfusion system ensuring HOPE of the resting donor heart. The donor hearts in the control group underwent ischaemic SCS according to standard practices. The primary outcome was time to first event of a composite of either cardiac-related death, moderate or severe primary graft dysfunction (PGD) of the left ventricle, PGD of the right ventricle, acute cellular rejection at least grade 2R, or graft failure (with use of mechanical circulatory support or re-transplantation) within 30 days after transplantation. We included all patients who were randomly assigned, fulfilled inclusion and exclusion criteria, and received a transplant in the primary analysis and all patients who were randomly assigned and received a transplant in the safety analyses. This trial was registered with ClicalTrials.gov (NCT03991923) and is ongoing. FINDINGS: A total of 229 patients were enrolled between Nov 25, 2020, and May 19, 2023. The primary analysis population included 204 patients who received a transplant. There were no patients who received a transplant lost to follow-up. All 100 donor hearts preserved with HOPE were transplantable after perfusion. The primary endpoint was registered in 19 (19%) of 101 patients in the HOPE group and 31 (30%) of 103 patients in the SCS group, corresponding to a risk reduction of 44% (hazard ratio 0·56; 95% CI 0·32-0·99; log-rank test p=0·059). PGD was the primary outcome event in 11 (11%) patients in the HOPE group and 29 (28%) in the SCS group (risk ratio 0·39; 95% CI 0·20-0·73). In the HOPE group, 63 (65%) patients had a reported serious adverse event (158 events) versus 87 (70%; 222 events) in the SCS group. Major adverse cardiac transplant events were reported in 18 (18%) and 33 (32%) patients in the HOPE and SCS group (risk ratio 0·56; 95% CI 0·34-0·92). INTERPRETATION: Although there was not a significant difference in the primary endpoint, the 44% risk reduction associated with HOPE was suggested to be a clinically meaningful benefit. Post-transplant complications, measured as major adverse cardiac transplant events, were reduced. Analysis of secondary outcomes suggested that HOPE was beneficial in reducing primary graft dysfunction. HOPE in donor heart preservation addresses the existing challenges associated with graft preservation and the increasing complexity of donors and heart transplantation recipients. Future investigation will help to further elucidate the benefit of HOPE. FUNDING: XVIVO Perfusion.

Right Ventriculoarterial Coupling Surrogates and Long-Term Survival in LVAD Recipients: Results of the ASSIST-ICD Multicentric Registry.

BACKGROUND: Prediction of outcomes remains an unmet need in candidates for LVADs. The development of right-heart failure portends an excess in mortality rates, but imaging parameters of right ventricular systolic function have failed to demonstrate a prognostic role. By integrating pulmonary pressure, right ventriculoarterial coupling could fill this gap. METHODS: The ASSIST-ICD registry was used to test right ventriculoarterial coupling as a surrogate parameter at implantation for the prediction of all-cause mortality. RESULTS: The ratio of the tricuspid annular-plane systolic excursion over the estimated systolic pulmonary pressure (TAPSE/sPAP) was not associated with long-term survival in univariate analysis (P = 0.89), nor was the pulmonary artery pulsatility index (PAPi) (P = 0.13). Conversely, the ratio of the right atrial pressure over the pulmonary capillary wedge pressure (RAP/PCWP) was associated with all-cause mortality (P < 0.01). After taking tricuspid regurgitation severity, LVAD indication, LVAD model, age, blood urea nitrogen levels, and pulmonary vascular resistance into account, RAP/PCWP remained associated with survival (HR 1.35 [1.10 - 1.65]; P < 0.01). CONCLUSION: Among pre-implant RVAC surrogates, only RAP/PCWP was associated with long-term all-cause mortality in LVAD recipients. This association was independent of established risk factors.

Healthcare-associated infections in patients with severe COVID-19 supported with extracorporeal membrane oxygenation: a nationwide cohort study.

BACKGROUND: Both critically ill patients with coronavirus disease 2019 (COVID-19) and patients receiving extracorporeal membrane oxygenation (ECMO) support exhibit a high incidence of healthcare-associated infections (HAI). However, data on incidence, microbiology, resistance patterns, and the impact of HAI on outcomes in patients receiving ECMO for severe COVID-19 remain limited. We aimed to report HAI incidence and microbiology in patients receiving ECMO for severe COVID-19 and to evaluate the impact of ECMO-associated infections (ECMO-AI) on in-hospital mortality. METHODS: For this study, we analyzed data from 701 patients included in the ECMOSARS registry which included COVID-19 patients supported by ECMO in France. RESULTS: Among 602 analyzed patients for whom HAI and hospital mortality data were available, 214 (36%) had ECMO-AI, resulting in an incidence rate of 27 ECMO-AI per 1000 ECMO days at risk. Of these, 154 patients had bloodstream infection (BSI) and 117 patients had ventilator-associated pneumonia (VAP). The responsible microorganisms were Enterobacteriaceae (34% for BSI and 48% for VAP), Enterococcus species (25% and 6%, respectively) and non-fermenting Gram-negative bacilli (13% and 20%, respectively). Fungal infections were also observed (10% for BSI and 3% for VAP), as were multidrug-resistant organisms (21% and 15%, respectively). Using a Cox multistate model, ECMO-AI were not found associated with hospital death (HR = 1.00 95% CI [0.79-1.26], p = 0.986). CONCLUSIONS: In a nationwide cohort of COVID-19 patients receiving ECMO support, we observed a high incidence of ECMO-AI. ECMO-AI were not found associated with hospital death. Trial registration number NCT04397588 (May 21, 2020).

Thromboembolic events after major bleeding events in patients with mechanical heart valves: a 13-year analysis.

Anticoagulation in patients with mechanical heart valves (MHV) is associated with a risk of major bleeding episodes (MBE). In case of MBE, anticoagulant interruption is advocated. However, there is lack of data regarding the thrombo-embolic events (TE) risk associated with anticoagulant interruption. The main objective of the study was to evaluate the rate and risk factors of 6-months of TEs in patients with MHV experiencing MBE. This observational study was conducted over a 13-year period. Adult patients with a MHV presenting with a MBE were included. The main study endpoint was 6-month TEs, defined by clinical TEs or an echocardiographic documented thrombosis, occurring during an ICU stay or within 6-months. Thromboembolic events were recorded at ICU discharge, and 6 months after discharge. Seventy-nine MBEs were analysed, the rate of TEs at 6-months was 19% CI [11-29%]. The only difference of presentation and management between 6-month TEs and free-TE patients was the time without effective anticoagulation (TWA). The Receiver Operator Characteristic curve identified the value of 122 h of TWA as a cut-off. The multivariate analysis identified early bleeding recurrences (OR 3.62, 95% CI [1.07-12.25], p = 0.039), and TWA longer than 122 h (OR 4.24, 95% CI [1.24-14.5], p = 0.021), as independent risk factors for 6-month TEs. A higher rate of TE was associated with anticoagulation interruption longer than 5 days and early bleeding recurrences. However, the management should still be personalized and discussed for each case given the heterogeneity of causes of MBE and possibilities of haemostatic procedures.

Femoro-axillary versus femoro-femoral veno-arterial extracorporeal membrane oxygenation for refractory cardiogenic shock: A monocentric retrospective study.

RATIONALE: For veno-arterial extracorporeal membrane oxygenation (ECMO), the femoral artery is the preferred cannulation site (femoro-femoral: Vf-Af). This results in retrograde aortic flow, which increases the left ventricular afterload and can lead to severe pulmonary edema and thrombosis of the cardiac chambers. Right axillary artery cannulation (femoral-axillary: Vf-Aa) provides partial anterograde aortic flow, which may prevent some complications. This study aimed to compare the 90-day mortality and complication rates between VF-AA and VF-AF. METHODS: Consecutive adult patients with cardiogenic shock who received peripheral VA-ECMO between 2013 and 2019 at our institution were retrospectively included. The exclusion criteria were refractory cardiac arrest, multiple VA-ECMO implantations due to vascular access changes, weaning failure, or ICU readmission. A statistical approach using inverse probability of treatment weighting was used to estimate the effect of the cannulation site on the outcomes. The primary endpoint was the 90-day mortality. The secondary endpoints were vascular access complications, stroke, and other complications related to retrograde blood flow. Outcomes were estimated using logistic regression analysis. RESULTS: VA-ECMO was performed on 534 patients. Patients with refractory cardiac arrest (n = 77 (14%)) and those supported by multiple VA-ECMO (n = 92, (17%)) were excluded. Out of the 333 patients studied (n = 209 Vf-Aa; n = 124 VF-AF), the main indications for VA-ECMO implantation were post-cardiotomy (33%, n = 109), dilated cardiomyopathy (20%, n = 66), post-cardiac transplantation (15%, n = 50), acute myocardial infarction (14%, n = 46) and other etiologies (18%, n = 62). The median SOFA score was 9 [7-11], and the crude 90-day mortality rate was 53% (n = 175). After IPTW, the 90-day mortality was similar in the Vf-Aa and VF-AF groups (54% vs 58%, IPTW-OR = 0.84 [0.54-1.29]). Axillary artery cannulation was associated with significantly fewer local infections (OR = 0.21, 95% CI:0.09-0.51), limb ischemia (OR = 0.37, 95% CI:0.17-0.84), bowel ischemia (OR = 0.16, 95% CI:0.05-0.51) and pulmonary edema (OR = 0.52, 95% CI:0.29-0.92) episodes, but with a higher rate of stroke (OR = 2.87, 95% CI:1.08-7.62) than femoral artery cannulation. CONCLUSION: Compared to VF-AF, axillary cannulation was associated with similar 90-day mortality rates. The high rate of stroke associated with axillary artery cannulation requires further investigation.

Impact of Prone Position in COVID-19 Patients on Extracorporeal Membrane Oxygenation.

OBJECTIVES: Prone positioning and venovenous extracorporeal membrane oxygenation (ECMO) are both useful interventions in acute respiratory distress syndrome (ARDS). Combining the two therapies is feasible and safe, but the effectiveness is not known. Our objective was to evaluate the potential survival benefit of prone positioning in venovenous ECMO patients cannulated for COVID-19-related ARDS. DESIGN: Retrospective analysis of a multicenter cohort. PATIENTS: Patients on venovenous ECMO who tested positive for severe acute respiratory syndrome coronavirus 2 by reverse transcriptase polymerase chain reaction or with a diagnosis on chest CT were eligible. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients on venovenous ECMO for respiratory failure in whom prone position status while on ECMO and in-hospital mortality were known were included. Of 647 patients in 41 centers, 517 were included. Median age was 55 (47-61), 78% were male and 95% were proned before cannulation. After cannulation, 364 patients (70%) were proned and 153 (30%) remained in the supine position for the whole ECMO run. There were 194 (53%) and 92 (60%) deaths in the prone and the supine groups, respectively. Prone position on ECMO was independently associated with lower in-hospital mortality (odds ratio = 0.49 [0.29-0.84]; p = 0.010). In 153 propensity score-matched pairs, mortality rate was 49.7% in the prone position group versus 60.1% in the supine position group (p = 0.085). Considering only patients alive at decannulation, propensity-matched proned patients had a significantly lower mortality rate (22.4% vs 37.8%; p = 0.029) than nonproned patients. CONCLUSIONS: Prone position may be beneficial in patients supported by venovenous ECMO for COVID-19-related ARDS but more data are needed to draw definitive conclusions.

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.

Extracorporeal Membrane Oxygenation for Respiratory Failure Related to COVID-19: A Nationwide Cohort Study.

BACKGROUND: Despite expanding use, knowledge on extracorporeal membrane oxygenation support during the COVID-19 pandemic remains limited. The objective was to report characteristics, management, and outcomes of patients receiving extracorporeal membrane oxygenation with a diagnosis of COVID-19 in France and to identify pre-extracorporeal membrane oxygenation factors associated with in-hospital mortality. A hypothesis of similar mortality rates and risk factors for COVID-19 and non-COVID-19 patients on venovenous extracorporeal membrane oxygenation was made. METHODS: The Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome-Coronavirus 2 (ECMOSARS) registry included COVID-19 patients supported by extracorporeal membrane oxygenation in France. This study analyzed patients included in this registry up to October 25, 2020, and supported by venovenous extracorporeal membrane oxygenation for respiratory failure with a minimum follow-up of 28 days after cannulation. The primary outcome was in-hospital mortality. Risk factors for in-hospital mortality were analyzed. RESULTS: Among 494 extracorporeal membrane oxygenation patients included in the registry, 429 were initially supported by venovenous extracorporeal membrane oxygenation and followed for at least 28 days. The median (interquartile range) age was 54 yr (46 to 60 yr), and 338 of 429 (79%) were men. Management before extracorporeal membrane oxygenation cannulation included prone positioning for 411 of 429 (96%), neuromuscular blockage for 419 of 427 (98%), and NO for 161 of 401 (40%). A total of 192 of 429 (45%) patients were cannulated by a mobile extracorporeal membrane oxygenation unit. In-hospital mortality was 219 of 429 (51%), with a median follow-up of 49 days (33 to 70 days). Among pre-extracorporeal membrane oxygenation modifiable exposure variables, neuromuscular blockage use (hazard ratio, 0.286; 95% CI, 0.101 to 0.81) and duration of ventilation (more than 7 days compared to less than 2 days; hazard ratio, 1.74; 95% CI, 1.07 to 2.83) were independently associated with in-hospital mortality. Both age (per 10-yr increase; hazard ratio, 1.27; 95% CI, 1.07 to 1.50) and total bilirubin at cannulation (6.0 mg/dl or more compared to less than 1.2 mg/dl; hazard ratio, 2.65; 95% CI, 1.09 to 6.5) were confounders significantly associated with in-hospital mortality. CONCLUSIONS: In-hospital mortality was higher than recently reported, but nearly half of the patients survived. A high proportion of patients were cannulated by a mobile extracorporeal membrane oxygenation unit. Several factors associated with mortality were identified. Venovenous extracorporeal membrane oxygenation support should be considered early within the first week of mechanical ventilation initiation.

Extracorporeal Membrane Oxygenation to Support Life-Threatening Drug-Refractory Electrical Storm.

OBJECTIVES: Despite rapid implementation of anti-arrhythmic treatment and sedation and controlling the triggering event, rare patients develop treatment-refractory electrical storm and their hemodynamic instability prevents emergency catheter ablation. In that context, venoarterial extracorporeal membrane oxygenation could rapidly restore hemodynamics and tissue perfusion and reduce myocardial oxygen consumption, until adequate anti-arrhythmic drug levels are reached to safely perform catheter ablation. DESIGN: Retrospective, multicenter study over an 8-year period. SETTING: Two French tertiary care centers. PATIENTS: Eighty-three consecutive adults with venoarterial extracorporeal membrane oxygenation-supported treatment-refractory electrical storm (median [interquartile range] age, 55 yr [48-63 yr]). MEASUREMENTS AND MAIN RESULTS: Fifty-nine percent of these patients had acute ischemic cardiomyopathy and 66% underwent cardiopulmonary resuscitation prior to venoarterial extracorporeal membrane oxygenation initiation, with 18% cannulated during it. Fifty patients (60%) had ventricular tachycardia and/or ventricular fibrillation alternating with short periods of sinus rhythm and 33 (40%) had refractory ventricular tachycardia and/or ventricular fibrillation. Twelve patients (15%) underwent safe catheter ablation under venoarterial extracorporeal membrane oxygenation. After a median of 3 days (1-13 d) on extracorporeal membrane oxygenation support, 37 patients (45%) were successfully weaned off and 42% were alive 6 months post-ICU admission. Multivariable analysis retained ventricular tachycardia and/or ventricular fibrillation episodes alternating with short periods of sinus rhythm (odds ratio, 0.18; 95% CI, 0.06-0.52; p = 0.002) and age less than 50 years (odds ratio, 0.32; 95% CI, 0.18-0.89; p = 0.002) as being independent protective factors with 6-month survival, regardless of the underlying electrical storm cause. CONCLUSIONS: Among venoarterial extracorporeal membrane oxygenation-supported drug-refractory electrical storm patients, 42% survived 6 months post-ICU admission. Ventricular tachycardia and/or ventricular fibrillation episodes alternating with short periods of sinus rhythm and age less than 50 years were independently associated with better survival.

Implantable cardiac defibrillator leads dysfunction after LVAD implantation.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) lead dysfunction has been reported after left ventricular assist device (LVAD) implantation in limited single-center studies. We aimed at describing and characterizing the incidence of ICD lead parameters dysfunction after LVAD implantation. METHODS: Among the 652 patients enrolled in the ASSIST-ICD study, only patients with an ICD prior to LVAD were included (n = 401). ICD lead parameters dysfunction following LVAD implantation is defined as follows: (a) >50% decrease in sensing threshold, (b) pacing lead impedance increase/decrease by >100Ω, and (c) >50% increase in pacing threshold. RESULTS: One hundred twenty-two patients with an ICD prior to LVAD had available ICD interrogation reports prior and after LVAD. A total of 67 (55%) patients exhibited at least one significant lead dysfunction: 17 (15%) exhibited >50% decrease in right ventricular (RV) sensing, 51 (42%) had >100 Ω increase/decrease in RV pacing impedance, and 24 (20%) experienced >50% increase in RV pacing threshold. A total of 52 patients experienced ventricular arrhythmia during follow-up and all were successfully detected and treated by the device. All lead dysfunction could be managed conservatively. CONCLUSION: More than 50% of LVAD-recipients may experience >1 significant change in lead parameters but none had severe clinical consequences.

Early EEG for Prognostication Under Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND/OBJECTIVES: Tools for prognostication of neurologic outcome of adult patients under venoarterial ECMO (VA-ECMO) have not been thoroughly investigated. We aimed to determine whether early standard electroencephalography (stdEEG) can be used for prognostication in adults under VA-ECMO. METHODS: Prospective single-center observational study conducted in two intensive care units of a university hospital, Paris, France. Early stdEEG was performed on consecutive adult patients treated with VA-ECMO for refractory cardiogenic shock or refractory cardiac arrest. The association between stdEEG findings and unfavorable outcome was investigated. The primary endpoint was 28-day mortality. The secondary endpoint was severe disability or death at 90 days, defined by a score of 4-6 on the modified Rankin scale. RESULTS: A total of 122 patients were included, of whom 35 (29%) received cardiopulmonary resuscitation before VA-ECMO cannulation. Main stdEEG findings included low background frequency ≤ 4 Hz (n = 27, 22%) and background abnormalities, i.e., a discontinuous (n = 20, 17%) and/or an unreactive background (n = 12, 10%). Background abnormalities displayed better performances for prediction of unfavorable outcomes, as compared to clinical parameters at time of recording. An unreactive stdEEG background in combination with a background frequency ≤ 4 Hz had a false positive rate of 0% for prediction of unfavorable outcome at 28 days and 90 days, with sensitivities of 8% and 6%, respectively. After adjustment for confounders, a lower background frequency was independently associated with unfavorable outcome at 28 days (adjusted odds ratio per 1-Hz increment, 95% CI 0.71, 0.52-0.97), whereas no such independent association was observed at 90 days. CONCLUSION: Standard EEG abnormalities recorded at time of VA-ECMO initiation are predictive of unfavorable outcomes. However, the low sensitivity of these parameters highlights the need for a multimodal evaluation for improving management of care and prognostication.

Risk factors and prognostic impact of left ventricular assist device-associated infections.

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 received HeartMate II (82.1%) or HeartWare (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.

Waitlist Outcomes in Candidates With Rare Causes of Heart Failure After Implementation of the 2018 French Heart Allocation Scheme.

BACKGROUND: In 2018, an algorithm-based allocation system for heart transplantation (HT) was implemented in France. Its effect on access to HT of patients with rare causes of heart failure (HF) has not been assessed. METHODS: In this national study, including adults listed for HT between 2018 and 2020, we analyzed waitlist and posttransplant outcomes of candidates with rare causes of HF (restrictive cardiomyopathy [RCM], hypertrophic cardiomyopathy, and congenital heart disease). The primary end point was death on the waitlist or delisting for clinical deterioration. Secondary end points included access to HT and posttransplant mortality. The cumulative incidence of waitlist mortality estimated with competing risk analysis and incidence of transplantation were compared between diagnosis groups. The association of HF cause with outcomes was determined by Fine-Gray or Cox models. RESULTS: Overall, 1604 candidates were listed for HT. At 1 year postlisting, 175 patients met the primary end point and 1040 underwent HT. Candidates listed for rare causes of HF significantly differed in baseline characteristics and had more frequent score exceptions compared with other cardiomyopathies (31.3%, 32.0%, 36.4%, and 16.7% for patients with hypertrophic cardiomyopathy, RCM, congenital heart disease, and other cardiomyopathies). The cumulative incidence of death on the waitlist and probability of HT were similar between diagnosis groups (P=0.17 and 0.40, respectively). The adjusted risk of death or delisting for clinical deterioration did not significantly differ between candidates with rare and common causes of HF (subdistribution hazard ratio (HR): hypertrophic cardiomyopathy, 0.51 [95% CI, 0.19-1.38]; P=0.18; RCM, 1.04 [95% CI, 0.42-2.58]; P=0.94; congenital heart disease, 1.82 [95% CI, 0.78-4.26]; P=0.17). Similarly, the access to HT did not significantly differ between causes of HF (hypertrophic cardiomyopathy: HR, 1.18 [95% CI, 0.92-1.51]; P=0.19; RCM: HR, 1.19 [95% CI, 0.90-1.58]; P=0.23; congenital heart disease: HR, 0.76 [95% CI, 0.53-1.09]; P=0.14). RCM was an independent risk factor for 1-year posttransplant mortality (HR, 2.12 [95% CI, 1.06-4.24]; P=0.03). CONCLUSIONS: Our study shows equitable waitlist outcomes among HT candidates whatever the indication for transplantation with the new French allocation scheme.

Sex differences and outcomes in surgical infective endocarditis.

BACKGROUND: Cardiac surgery for infective endocarditis (IE) is associated with significant hospital mortality, and female sex may be associated with worse outcomes. However, the impact of sex on the presenting characteristics, management, and outcomes of patients operated on for acute infective endocarditis (IE) has not been adequately studied. OBJECTIVES: The goal of our study was to analyse differences in management and outcome of IE between women and men who undergo surgery. METHODS: Clinical data of 717 patients undergoing cardiac surgery for IE between December 2005 and December 2019 were prospectively collected. Sex-related postoperative outcomes including in-hospital mortality were recorded. Univariable and multivariable analyses were performed to identify potential sex-related determinant of in-hospital mortality. RESULTS: In all, 532 male patients (74.2%) and 185 female patients (25.8%) underwent surgery for IE. At baseline, women had more frequent mitral regurgitation with 63 patients (34.1%) than men with 135 patients (25.4%) (P = 0.002). Female sex was associated with higher in-hospital mortality (23.2% versus 17.3%, P = 0.049). However, multivariable analysis revealed age (P < 0.01), antibiotics < 7 days before surgery (P = 0.01) and staphylococcal IE (P < 0.01) but not female sex (P = 0.99) as independent determinants of hospital mortality. CONCLUSIONS: In this study of patients operated-on for IE, female sex was associated with more severe manifestations of IE and significantly higher in-hospital mortality. However, after multivariable analysis, initial presentation, but not sex, seemed to determine clinical outcomes.

Long-term Oral Suppressive Antimicrobial Therapy in Infective Endocarditis (SATIE Study): An Observational Study.

Background: The role of suppressive antimicrobial therapy (SAT) in infective endocarditis (IE) management has yet to be defined. The objective of this study was to describe the use of SAT in an IE referral center and the patients' outcomes. Methods: We conducted a retrospective observational study in a French IE referral center (Paris). All patients with IE who received SAT between 2016 and 2022 were included. Results: Forty-two patients were included (36 male [86%]; median age [interquartile range {IQR}], 73 [61-82] years). The median Charlson Comorbidity Index score (IQR) was 3 (1-4). Forty patients (95%) had an intracardiac device. The most frequent microorganisms were Enterococcus faecalis (15/42, 36%) and Staphylococcus aureus (12/42, 29%). SAT indications were absence of surgery despite clinical indication (28/42, 67%), incomplete removal of prosthetic material (6/42, 14%), uncontrolled infection source (4/42, 10%), persistent abnormal uptake on nuclear imaging (1/42, 2%), or a combination of the previous indications (3/42, 7%). Antimicrobials were mainly doxycycline (19/42, 45%) and amoxicillin (19/42, 45%). The median follow-up time (IQR) was 398 (194-663) days. Five patients (12%) experienced drug adverse events. Five patients (12%) presented with a second IE episode during follow-up, including 2 reinfections (different bacterial species) and 3 possible relapses (same bacterial species). Fourteen patients (33%) in our cohort died during follow-up. Overall, the 1-year survival rate was 84.3% (73.5%-96.7%), and the 1-year survival rate without recurrence was 74.1% (61.4%-89.4%). Conclusions: SAT was mainly prescribed to patients with cardiac devices because of the absence of surgery despite clinical indication. Five (12%) breakthrough second IE episodes were reported. Prospective comparative studies are required to guide this empirical practice.

Acute Pulmonary Edema After Double Mechanical Valve Replacement.

We report a case of a 16-year-old man in cardiogenic shock secondary to On-X mitral prosthesis dysfunction due to leaflet embolization through aortic mechanical prosthesis. He underwent an emergency redo mitral valve replacement and, a few days later, leaflet removal by open aortic surgery with full recovery.

Association of Sepsis With Neurologic Outcomes of Adult Patients Treated With Venoarterial Extracorporeal Membrane Oxygnenation.

OBJECTIVES: Neurologic outcomes of patients under venoarterial extracorporeal membrane oxygenation (VA-ECMO) may be worsened by secondary insults of systemic origin. We aimed to assess whether sepsis, commonly observed during ECMO support, is associated with brain injury and outcomes. DESIGN: Single-center cohort study of the "exposed-non-exposed" type on consecutive adult patients treated by VA-ECMO. SETTING: Medical ICU of a university hospital, France, 2013-2020. PATIENTS: Patients with sepsis at the time of VA-ECMO cannulation ("sepsis" group) were compared with patients without sepsis ("no sepsis" group). The primary outcome measure was poor functional outcome at 90 days, defined by a score greater than or equal to 4 on the modified Rankin scale (mRS), indicating severe disability or death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 196 patients were included ("sepsis," n = 128; "no sepsis," n = 68), of whom 87 (44.4%) had presented cardiac arrest before VA-ECMO cannulation. A poor functional outcome (mRS ≥ 4) was observed in 99 of 128 patients (77.3%) of the "sepsis" group and 46 of 68 patients (67.6%) of the "no sepsis" group (adjusted logistic regression odds ratio (OR) 1.21, 95% CI, 0.58-2.47; inverse probability of treatment weighting (IPTW) OR 1.24; 95% CI, 0.79-1.95). Subsequent analyses performed according to pre-ECMO cardiac arrest status suggested that sepsis was independently associated with poorer functional outcomes in the subgroup of patients who had experienced pre-ECMO cardiac arrest (adjusted logistic regression OR 3.44; 95% CI, 1.06-11.40; IPTW OR 3.52; 95% CI, 1.68-7.73), whereas no such association was observed in patients without pre-ECMO cardiac arrest (adjusted logistic regression OR 0.69; 95% CI, 0.27-1.69; IPTW OR 0.76; 95% CI, 0.42-1.35). Compared with the "no sepsis" group, "sepsis" patients presented a significant increase in S100 calcium-binding protein beta concentrations at day 1 (0.94 µg/L vs. 0.52 µg/L, p = 0.03), and more frequent EEG alterations (i.e., severe slowing, discontinuous background, and a lower prevalence of sleep patterns), suggesting brain injury. CONCLUSION: We observed a detrimental role of sepsis on neurologic outcomes in the subgroup of patients who had experienced pre-ECMO cardiac arrest, but not in other patients.

Extracorporeal membrane oxygenation (ECMO) during aplasia: A bridge towards myopericarditis recovery after autologous hematopoietic stem cell transplant for systemic sclerosis and recent Coronarovirus disease (COVID-19) vaccination.

Systemic sclerosis (SSc) is a rare autoimmune disease (AD), characterised by early diffuse vasculopathy, activation of the immune response and progressive skin and internal organ fibrosis. In severe progressive diffuse SSc (dSSc), autologous hematopoietic stem cell transplantation (aHSCT) improves survival, despite its own risk of complications and transplant related mortality (TRM). We present herein the case of a dSSc patient undergoing aHSCT with low dose cyclophosphamide conditioning and sudden acute myopericarditis and cardiogenic shock, four weeks after a second mRNA SARS-CoV-2 vaccine (Pfizer) injection. Four days of extracorporeal membrane oxygenation (ECMO) support during the aplasia period, allowed to observe full cardiac function recovery and progressive SSc rehabilitation with sustained disease response at 30 months follow-up. This report illustrates, for the first time to our knowledge, that ECMO can be indicated despite aplasia during aHSCT and successfully used as a bridge towards heart function recovery in highly selected and fragile AD patients. We review the factors that may contribute to endothelial and myocardial stunning and acute reversible cardiac failure in SSc and aggravate intrinsic endothelial injury during the aHSCT procedure. These classically include: cyclophosphamide drug toxicity, viral infections and autoimmune activation with disease flair per se. In the COVID-19 pandemic times, acute myocarditis due to recent viral infection or mRNA vaccine per se, must also be considered.