Outcome of primary graft dysfunction rescued by venoarterial extracorporeal membrane oxygenation after heart transplantation.

BACKGROUND: Primary graft dysfunction remains the leading cause of 30-day mortality after heart transplantation. Few data have been published about the clinical outcome of severe primary graft dysfunction treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). AIM: To evaluate the prevalence and outcome of severe primary graft dysfunction requiring VA-ECMO, and to identify factors associated with hospital mortality. METHODS: We performed an observational analysis of our institutional database of VA-ECMO for primary graft dysfunction after heart transplantation. Patients with severe primary graft dysfunction, according to the International Society for Heart and Lung Transplantation classification, were included. The primary outcome was survival to hospital discharge. Risk factors for in-hospital mortality were searched with multiple logistic regression analysis using backward stepwise variable elimination. RESULTS: Of the 397 patients who had heart transplantation between January 2007 and December 2018, 60 (15.1%) developed severe primary graft dysfunction requiring VA-ECMO. The median age was 52 (interquartile range 39-59) years, and 73.3% were male. Thirty-nine (65.0%) patients were weaned after a mean duration of VA-ECMO support of 7.2±6.0 days. Thirty-two (53.3%) patients were alive at hospital discharge. Inotropic support in the recipient before heart transplantation (odds ratio [OR] 3.88, 95% confidence interval [CI] 1.04-14.44; P=0.04), total ischaemic time (OR 0.99, 95% CI 0.99-1.00; P=0.01) and 48-hour total blood transfusion (OR 1.14, 95% CI 1.04-1.26; P=0.01) were independent predictors of in-hospital mortality. CONCLUSIONS: Severe primary graft dysfunction requiring VA-ECMO is frequent after heart transplantation. Survival to hospital discharge after VA-ECMO for severe primary graft dysfunction is satisfactory in such a critically ill population.

Prognosis of Advanced Heart Failure Patients according to Their Hemodynamic Profile Based on the Modified Forrester Classification.

INTRODUCTION: Heart transplantation (HT) remains the gold-standard treatment but is conditioned by organ shortage. This study aimed to evaluate the value of Forrester classification and determine which congestion criteria had the best prognostic value to predict cardiorenal events on heart transplant waiting list. METHODS AND RESULTS: One hundred consecutive patients (54 years old, 72% men) with available right heart catheterization (RHC) listed in our center for HT between 2014 and 2019 were included. Cardiac catheterization measurements were obtained at the time of HT listing evaluation. Patients were classified according to perfusion and congestion status in four groups: "warm and dry", "warm and wet", "cold and dry", and "cold and wet". pWet was used to classify patients with pulmonary congestion and sWet for systemic congestion. The primary endpoint was the rate of a composite criteria of cardiogenic shock, acute kidney injury, and acute heart failure. Secondary endpoint was the incidence of waitlist death, emergency HT, or left ventricular assist device (LVAD) implantation at 12 months evaluated by Kaplan-Meier curves and log-rank test. Only Forrester classification according to systemic congestion was associated with the primary composite endpoint (p = 0.011), while patients' profile according to pulmonary congestion was not (p = 0.331). Similarly, only the Forrester classification according to systemic congestion predicted waitlist death, emergency HT, or LVAD implantation at 12 months, with p = 0.010 and p = 0.189 for systemic and pulmonary congestion, respectively. Moreover, systemic congestion was the main driver of cardiorenal events on waitlist. CONCLUSIONS: Forrester classification according to systemic congestion is associated with cardiorenal outcomes in patients listed for heart transplant and the risk of waitlist death, emergency HT, or LVAD implantation at 12 months.

De Novo Complement-Binding Anti-HLA Antibodies in Heart Transplanted Patients Is Associated with Severe Cardiac Allograft Vasculopathy and Poor Long-Term Survival.

Introduction: De novo anti-HLA donor specific antibodies (DSA) have been inconsistently associated with cardiac allograft vasculopathy (CAV) and long-term mortality. We tested whether C3d-binding de novo DSA were associated with CAV or long-term-survival. Methods: We included 282 consecutive patients without preformed DSA on coronary angiography between 2010 and 2012. Angiographies were classified according to CAV ISHLT grading. The primary outcome was a composite criterion of severe CAV or mortality. As the impact of de novo antibodies should be assessed only after appearance, we used a Cox regression with time-dependent covariables. Results: Of the 282 patients, 51(18%) developed de novo DSA during follow-up, 29 patients had DSA with C3d-binding ability (DSA+C3d+), and 22 were without C3d-binding ability (DSA+C3d-). Compared with patients without DSA, DSA+C3d+ patients had an increased risk for the primary outcome of severe CAV or mortality (adjusted HR = 4.31 (2.40−7.74) p < 0.001) and long-term mortality (adjusted HR = 3.48 (1.97−6.15) p < 0.001) whereas DSA+C3d- did not (adjusted HR = 1.04 (0.43−2.47) p = 0.937 for primary outcome and HR = 1.08 (0.45−2.61) p = 0.866 for mortality). Conclusion: According to this large monocentric study in heart transplant patients, donor specific antibodies were associated with worse clinical outcome when binding complement. DSA and their complement-binding ability should thus be screened for to optimize heart transplant patient follow-up.

Prevalence and determinants of iron deficiency in cardiac amyloidosis.

AIMS: Iron deficiency (ID) is common in patient with chronic heart failure (HF) and has been widely studied. In contrast, data concerning ID in cardiac amyloidosis (CA) are limited. Amyloidosis is a severe and fatal systemic disease, characterized by an accumulation of amyloid fibrils in various tissues/organs, including nerves, kidneys, gastrointestinal tract, and heart. Amyloid deposits in the heart eventually cause HF. The main subtypes of CA are light chain (AL), hereditary transthyretin (ATTRv), and wild-type transthyretin (ATTRwt). We performed this study to determine the prevalence, clinical outcome (all-cause mortality), and determinants of ID among the three main subtypes of CA. METHODS AND RESULTS: Iron deficiency status were analysed in 816 CA patients enrolled at the French Referral Centre for Cardiac Amyloidosis: 271 (33%) had AL, 164 (20%) ATTRv, and 381 (47%) ATTRwt. ID affected 49% of CA patients, 45% with AL, 58% with ATTRv, and 48% with ATTRwt. We identified ATTR status (ATTRv P = 0.003, ATTRwt P = 0.037), diabetes (P = 0.003), aspirin treatment (P = 0.009), haemoglobin levels (P = 0.006), and altered global longitudinal strain (P = 0.02) as independent ID determinants. There is no difference in all-cause mortality considering ID status. CONCLUSIONS: Iron deficiency is common in patients with CA, irrespective of the subtype. Patients seem more likely to have ID if diagnosed with ATTR, if diabetic, and/or treated with aspirin. In CA, the benefit of intravenous iron therapy, for ID, on morbidity and mortality needs further study.

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.

Haemodynamic parameters associated with renal function prior to and following heart transplantation.

AIMS: Abnormal renal function is a common feature in patients on heart transplant waiting lists. This study aimed to identify the haemodynamic parameters associated with decreased estimated glomerular filtration rate (eGFR) in patients listed for heart transplantation (HT) and renal function improvement following HT. METHODS AND RESULTS: A total of 176 adults (52 years old, 81% men) with available right heart catheterization (RHC) listed in our centre for HT between 2014 and 2019 were studied. Cardiac catheterization measurements were obtained at time of HT listing evaluation. Changes in renal function were assessed between RHC and 6 months after HT. Median eGFR was 63 mL/min/1.73 m2 at time of RHC. Central venous pressure > 10 mmHg was associated with a two-fold increase in the likelihood of eGFR < 60 mL/min/1.73 m2 at time of RHC (adjusted odd ratio, 2.2; 95% confidence interval, 1.1-4.7; P = 0.04). In the 134 patients (76%) who underwent HT during follow-up, eGFR decreased by 7.9 ± 29.7 mL/min/1.73 m2 from RHC to 6 months after HT. In these patients, low cardiac index (<2.1 L/min/m2 ) at initial RHC was associated with a (adjusted) 6 month post-HT eGFR improvement of 12.2 mL/min/1.73 m2 (P = 0.018). Patients with eGFR < 60 mL/min/1.73 m2 and low cardiac index at time of RHC exhibited the greatest eGFR improvement (delta eGFR = 18.3 mL/min/1.73 m2 ) while patients with eGFR ≥ 60 mL/min/1.73 m2 and normal cardiac index had a marked decrease in eGFR (delta eGFR = -27.7 mL/min/1.73 m2 , P < 0.001). CONCLUSIONS: Central venous pressure is the main haemodynamic parameter associated with eGFR < 60 mL/min/1.73 m2 in patients listed for HT. Low cardiac index prior to HT is associated with post-transplant renal function recovery.

Semi-industrial development of nutritious and healthy seafood dishes from sustainable species.

This study aimed to devise innovative, tailor-made, appealing, tasty and semi-industrialized dishes, using sustainable and under-utilized seafood species (bib, common dab, common carp, blue mussel and blue whiting), that can meet the specific nutritional and functional needs of children (8-10-years), pregnant women (20-40-years) and seniors (≥60-years). Hence, contests were organised among cooking schools from 6 European countries and the best recipes/dishes were reformulated, semi-industrially produced and chemically and microbiologically evaluated. The dishes intended for: (i) children and pregnant women had EPA + DHA and I levels that reached the target quantities, supporting the claim as "high in I"; and (ii) seniors were "high in protein" (24.8%-Soup_S and 34.0%-Balls_S of the energy was provided by proteins), "high in vitamin B12", and had Na contents (≤0.4%) below the defined limit. All dishes reached the vitamin D target value. Sausages_C, Roulade_P, Fillet_P and Balls_S had a well-balanced protein/fat ratio. Roulade_P presented the highest n-3 PUFA/n-6 PUFA ratio (3.3), while Sausages_C the lowest SFA/UNS ratio (0.2). Dishes were considered safe based on different parameters (e.g. Hg-T, PBDEs, Escherichia coli). All represent dietary sources contributing to meet the reference intakes of target nutrients (33->100%), providing valuable options to overcome nutritional and functional imbalances of the three groups.

Outcome Predictors and Safety of Home Dobutamine Intravenous Infusion in End Stage Heart Failure Patients.

Patients in end-stage heart failure can experiment cardiogenic shock and may not be weanable from dobutamine. The fate of these patients is a challenge for doctors, patients, family, and the institution. Dobutamine use at home can be a solution. The aim of the present study was to assess the outcome, biological predictors, and safety of dobutamine use at home in dobutamine-dependent patients. All consecutive dobutamine-dependent patients discharged with continuous home intravenous dobutamine, from a single tertiary center between February 2014 and November 2019, were retrospectively analyzed. A total of 19 patients (age 65 ± 10 years) were followed for one year. At one-year, the survival rate was 32%, (6/19). Five (26%) patients had an adverse event related to the intravenous catheter. In a multivariate logistic regression analysis, the combination of a glomerular filtration rate >60 mL/min and a brain natriuretic peptide level <1000 ng/L, were highly predictive of one-year survival (HR = 10.87, IC95% (5.78-36.44), p < 0.001). Management of dobutamine-unweanable patients after cardiogenic shock may involve dobutamine at home to permit a home return. This strategy allows a significant survival and few readmissions, and, if eligible, access to surgical strategies, such as heart transplantation. Simple biological markers at discharge can identify severe patients to refer to palliative care and good responders.

ARNI Pre-Operative Use and Vasoplegic Syndrome in Patients Undergoing Heart Transplantation or Left Ventricular Assist Device Surgery.

Background: Vasoplegic syndrome after orthotopic heart transplantation (OHT) or left ventricular assist device (LVAD) implantation is a rare but highly lethal syndrome with complex etiologies. The objective of this study was to assess if the preoperative use of sacubitril-valsartan combination is associated with an increased vasoplegic syndrome (VS) frequency after OHT or LVAD implantation and its relationship with 30-day mortality. Methods: A retrospective review of perioperative data, between January 2016 and December 2017, from 73 consecutive OHT and LVAD surgery adult patients at our institution was performed. VS was defined as normal cardiac output with persistent low systemic resistance requiring a norepinephrine intravenous perfusion > 0.5 µg/kg/min and the absence of sepsis or hemorrhagic shock within 48 h after surgery. Patients were all followed-up for adverse events and all-cause mortality at 30 days. Results: In our cohort of 73 patients (median age 51.7 years, 65% male patients), 25 (34%) patients developed VS. Twenty-two (30.1%) patients were on ARNI at the time of surgery, 31 (42.5%) were on other RAS blockers, 12 (16.4%) were on norepinephrine and 8 (11%) had no pre-operative drug. The pre-operative use of any vasoactive agent, was not significantly associated with VS (OR = 1.36; IC95% [0.78; 2.35]; p = 0.38). The pre-operative use of an ARNI compared to all other groups was not significantly associated with VS (OR = 2.0; IC95% [0.71; 5.62]; p = 0.19). The pre-operative use of an ARNI compared to other RAS blockers was also not significantly associated with VS (OR = 1.25; IC95% [0.37; 4.26]; p = 0.72). At 30 days, 18 (24.7%) patients had died. The pre-operative treatment with ARNI, or other RAS inhibitors was associated with a significantly lower rate of death compared to the absence of treatment (HR = 0.11; IC95% [0.02; 0.55]; p = 0.009 for ARNI and HR = 0.20; IC95% [0.06; 0.69]; p = 0.011 for other RASi). Conclusions: Preoperative use of sacubitril-valsartan was not significantly associated with development of vasoplegic syndrome in patients undergoing OHT or LVAD surgery. Furthermore, our data suggests a significant 30-day survival benefit with efficient renin-angiotensin blockade before surgery.

Outcomes after extracorporeal life support for postcardiotomy cardiogenic shock.

BACKGROUND AND AIM OF THE STUDY: Extracorporeal life support (ECLS) may be necessary in refractory postcardiotomy cardiogenic shock (PCS) unresponsive to optimal medical treatment. We sought to analyze the results and temporal outcomes of ECLS for PCS. METHODS: We performed an observational analysis of our prospective database. In order to analyze the temporal trends of ECLS for PCS, patients were divided into two groups according to the period of ECLS implantation: Group I from January 2007-June 2012, Group II from July 2012-December 2017. The primary endpoint was survival to hospital discharge. RESULTS: During the study period, 90 patients required ECLS for PCS (Group I n = 29, 32%; Group II n = 61, 68%). Mean age was 57.5 ± 15.0 years with 62% of males. Preoperative characteristics were comparable over the two periods. A high proportion of patients were in NYHA class III/IV (61%) or cardiogenic shock (22%). Group II showed a significantly higher proportion of miscellaneous cardiac surgery operations (23 vs 3%, P = 0.031). Crossclamp and cardiopulmonary bypass times were significantly shorter in Group II (85.4 vs 114.2 min, P = 0.023 and 135.2 vs 184.2 min, P = 0.022, respectively). The complication rate during ECLS support was comparable between both groups. Successful weaning from ECLS could be accomplished in 45 (50%) patients (Group I = 52% vs Group II = 49%, P = 0.822) after a mean support of 6.4 days. Thirty-five (39%) patients survived to hospital discharge (Group I = 41% vs Group II = 38%, P = 0.738). CONCLUSIONS: Outcomes following ECLS remained stable over an 11-year period. ECLS may be limited in patients with severe preoperative cardiac dysfunction. Our data suggest that these patients may be better served with less invasive, percutaneous procedures.

Extracorporeal life support for primary graft dysfunction after heart transplantation.

OBJECTIVES: Survival after heart transplantation is steadily improving but primary graft dysfunction (PGD) is still a leading cause of death. Medical management seems useful in mild or moderate PGD, whereas extracorporeal life support (ECLS) could be suggested for severe PGD refractory to conventional treatment. Our aim is to present the results of ECLS for PGD after heart transplantation at a single-centre experience. METHODS: We performed an observational analysis of our local database. According to the International Society for Heart and Lung Transplantation classification, patients were divided into a left and biventricular failure (PGD-LV) or isolated right ventricular failure (PGD-RV) group. The primary end point was survival to hospital discharge. RESULTS: Between January 2010 and December 2016, 38 patients presented with PGD (PGD-LV n = 22, 58%; PGD-RV n = 16, 42%) requiring ECLS support. The mean age was 50.8 ± 12.4 years and 79% were males. Baseline characteristics were comparable between the 2 groups. PGD-LV patients displayed a significantly higher mortality rate on ECLS support as opposed to PGD-RV patients (46% vs 13%, P = 0.033). The rate of complications during ECLS support was comparable between the 2 groups. Twenty-three (61%) patients were successfully weaned from ECLS (PGD-LV = 50% vs PGD-RV = 75%, P = 0.111) after a mean support of 9.0 ± 6.4 days. Seventeen (45%) patients survived to hospital discharge (PGD-LV = 41% vs PGD-RV = 50%, P = 0.410). CONCLUSIONS: In case of severe PGD with various manifestations of ventricular failure refractory to conventional treatment, ECLS can be considered as a feasible option with satisfactory survival in this critically ill population.

High rate of arterial complications in patients supported with extracorporeal life support for drug intoxication-induced refractory cardiogenic shock or cardiac arrest.

BACKGROUND: Cardiac failure is still a leading cause of death in drug intoxication. Extracorporeal life support (ECLS) could be used as a rescue therapeutic option in patients developing refractory cardiogenic shock or cardiac arrest. The aim of this report is to present our results of ECLS in the setting of poisoning from cardiotoxic drugs. METHODS: We included in this analysis consecutive patients who received an ECLS for refractory cardiogenic shock or in-hospital cardiac arrest due to drug intoxication. The primary endpoint of our study was survival to hospital discharge with good neurological recovery after ECLS support. RESULTS: Between January 2010 and December 2015, we performed 12 ECLS. Mean age was 44.2±17.8 years and there was a predominance of females (66.7%). Drug intoxication was mainly due to beta-blockers and/or calcium channel inhibitors (83.3%) and 5 (41.7%) patients had multiple drugs overdose. Weaning rate and survival to hospital discharge with good neurological recovery were 75% (9 patients). Among patients weaned from ECLS, mean duration of support was 2.4±1.1 days. Three (25%) patients underwent ECLS implantation during cardiopulmonary resuscitation, 2 (66.6%) of them died while on mechanical circulatory support (MCS). Six (50%) patients developed lower limb ischemia. Each patient was managed with ECLS decannulation: 2 (16.7%) patients underwent a concomitant iliofemoral thrombectomy, 3 (25%) needed further fasciotomy and the remaining patient (8.3%) required an amputation. CONCLUSIONS: Refractory cardiogenic shock due to drug intoxication is still one of the best indications for ECLS owing to the satisfactory survival with good neurological outcome in such a critically ill population. Further data are however necessary in order to best understand the possible relation between drug intoxication and lower limb ischemia, which was quite superior to the reported rates.