Association of HbA1c and utilization of internal mammary arteries with wound infections in CABG.

Background: Deep sternal wound infection (DSWI) remains a serious complication after coronary artery bypass grafting (CABG). We herein aimed to stratify diabetic patients who underwent CABG using bilateral internal mammary artery (BIMA) for levels of glycated hemoglobin A1C (HbA1c) and compare postoperative outcomes. Methods: Between January 2010 and August 2020, 4,186 consecutive patients underwent isolated CABG at our center. In 3,229 patients, preoperative HbA1c levels were available. Primary endpoints were wound healing disorder (WHD), DSWI, and 30-day mortality. Patients were stratified according to preoperative HbA1c levels. Patients were further divided into subgroups according to utilization of BIMA. Results: After adjustment, no differences in mortality and stroke rates were seen between group 1 (HbA1c < 6.5%) vs. group 2 (HbA1c ≥ 6.5%). WHD was more frequent in group 2 [2.8 vs. 5.6%; adjusted p = 0.002; adjusted odds ratio (OR), 1.853 (1.243-2.711)] but not DSWI [1.0 vs. 1.5%; adjusted p = 0.543; adjusted OR, 1.247 (0.612-2.5409)]. BIMA use showed a higher rate of WHD [no BIMA: 3.0%; BIMA: 7.7%; adjusted p = 0.002; adjusted OR, 4.766 (1.747-13.002)] but not DSWI [no BIMA: 1.1%; BIMA: 1.8%; adjusted p = 0.615; adjusted OR, 1.591 (0.260-9.749)] in patients with HbA1c ≥ 6.5%. Conclusions: Intraoperative utilization of BIMA is not connected with an increase of DSWI but higher rates of WHD in patients with poor diabetic status and HbA1c ≥ 6.5%. Therefore, application of BIMA should be taken into consideration even in patients with poor diabetic status, while identification of special subsets of patients who are at particular high risk for DSWI is of paramount importance to prevent this serious complication.

[Role of Complement in Kidney Diseases - New Aspects]. / Die Rolle des Komplementsystems bei Nierenerkrankungen ­ Neue Aspekte.

Complement is a central part of the immune system. In the human body, complement is responsible for recognition of infectious microbes, for coordinating the adaptive immune response, controlling homeotic reactions and for the non-inflammatory removal of modified self-cells and infectious microbes. Complement is also closely linked to another proteolytic cascade, the coagulation system. Defective activation and altered complement regulation drives pathology of several severe human kidney diseases.This manuscript summarizes the latest developments on the role of complement in kidney diseases, on new complement inhibitors and on recent complement targeting therapies. In particular focusing on diseases (1) atypical Hemolytic Uremic Syndrome, (2) C3 Glomerulopathy, (3) Anti Neutrophil Cytoplasmic Antibody Mediated Vasculitis, (4) IgA Nephropathy, (5) Membranous Glomerulopathy, (6) Systemic Lupus Erythematosus, (7) Transplant rejection and (8) COVID 19 Infection-Triggered Kidney Diseases. More excitement is generated in this field, as more and more complement mediated diseases can be treated. Several complement targeting compounds are approved by the EMA and FDA and an increasing number of new candidates are in late phase clinical trials. In addition, clinical guidelines are developed for Diagnosis and Therapy of complement mediated diseases, new biomarkers are evaluated in clinical studies, and diagnostic guidelines are in development. The recent Covid infections showed a clear link of complement in thrombo inflammation, which ultimately results in kidney damage. These aspects have increased further the focus of complement inhibitors in COVID infections.

Antegrade axillary arterial perfusion in 3D endoscopic minimally-invasive mitral valve surgery.

Background: Minimally-invasive (MIS) mitral valve (MV) surgery has become standard therapy in many cardiac surgery centers. While femoral arterial perfusion is the preferred cannulation strategy in MIS mitral valve surgery, retrograde arterial perfusion is known to be associated with an increased risk for cerebral atheroembolism, particularly in atherosclerosis patients. Therefore, antegrade perfusion may be beneficial in such cases. This analysis aimed to compare outcomes of antegrade axillary vs. retrograde femoral perfusion in the MIS mitral valve surgery. Methods: This analysis includes 50 consecutive patients who underwent MIS between 2016 and 2020 using arterial cannulation of right axillary artery (Group A) due to severe aortic arteriosclerosis. Perioperative outcomes of the study group were compared with a historical control group of retrograde femoral perfusion (Group F) which was adjusted for age and gender (n = 50). Primary endpoint of the study was in-hospital mortality and perioperative cerebrovascular events. Results: Patients in group A had a significantly higher perioperative risk as compared to Group F (EuroSCORE II: 3.9 ± 2.5 vs. 1.6 ± 1.5; p = 0.001; STS-Score: 2.1 ± 1.4 vs. 1.3 ± 0.6; p = 0.023). Cardiopulmonary bypass time (group A: 172 ± 46; group F: 178 ± 51 min; p = 0.627) and duration of surgery (group A: 260 ± 65; group F: 257 ± 69 min; p = 0.870) were similar. However, aortic cross clamp time was significantly shorter in group A as compared to group F (86 ± 20 vs. 111 ± 29 min, p < 0.001). There was no perioperative stroke in either groups. In-hospital mortality was similar in both groups (group A: 1 patient; group F: 0 patients; p = 0.289). In group A, one patient required central aortic repair due to intraoperative aortic dissection. No further cardiovascular events occurred in Group A patients. Conclusion: Selective use of antegrade axillary artery perfusion in patients with systemic atherosclerosis shows similar in-hospital outcomes as compared to lower risk patients undergoing retrograde femoral perfusion. Patients with higher perioperative risk and severe atherosclerosis can be safely treated via the minimally invasive approach with antegrade axillary perfusion.

Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation With and Without Intra-Aortic Balloon Pump.

OBJECTIVES: To compare the outcomes of patients with postcardiotomy shock treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO) only compared with VA-ECMO and intra-aortic balloon pump (IABP). DESIGN: A retrospective multicenter registry study. SETTING: At 19 cardiac surgery units. PARTICIPANTS: A total of 615 adult patients who required VA-ECMO from 2010 to 2018. The patients were divided into 2 groups depending on whether they received VA-ECMO only (ECMO only group) or VA-ECMO plus IABP (ECMO-IABP group). MEASUREMENTS AND MAIN RESULTS: The overall series mean age was 63 ± 13 years, and 33% were female. The ECMO-only group included 499 patients, and 116 patients were in the ECMO-IABP group. Urgent and/or emergent procedures were more common in the ECMO-only group. Central cannulation was performed in 47% (n = 54) in the ECMO-IABP group compared to 27% (n = 132) in the ECMO-only group. In the ECMO-IABP group, 58% (n = 67) were successfully weaned from ECMO, compared to 46% (n = 231) in the ECMO-only group (p = 0.026). However, in-hospital mortality was 63% in the ECMO-IABP group compared to 65% in the ECMO-only group (p = 0.66). Among 114 propensity score-matched pairs, ECMO-IABP group had comparable weaning rates (57% v 53%, p = 0.51) and in-hospital mortality (64% v 58%, p = 0.78). CONCLUSIONS: This multicenter study showed that adjunctive IABP did not translate into better outcomes in patients treated with VA-ECMO for postcardiotomy shock.

Gender and the Outcome of Postcardiotomy Veno-arterial Extracorporeal Membrane Oxygenation.

OBJECTIVE: There is a paucity of sex-specific data on patients' postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO). The present study sought to assess this issue in a multicenter study. DESIGN: Retrospective, propensity score-matched analysis of an international registry. SETTING: Multicenter study, tertiary university hospitals. PARTICIPANTS: Data on adult patients undergoing postcardiotomy VA-ECMO. MEASUREMENTS AND MAIN RESULTS: Between January 2010 and March 2018, patients treated with postcardiotomy VA-ECMO at 17 cardiac surgery centers were analyzed. Index procedures considered were coronary artery bypass graft surgery, isolated valve surgery, their combination, and proximal aortic root surgery. Hospital and five-year mortality constituted the endpoints of interest. Propensity score matching was adopted with logistic regression. A total of 358 patients (mean age: 63.3 ± 12.3 years; 29.6% female) were identified. Among 94 propensity score-matched pairs, women had a higher hospital mortality (70.5% v 56.4%, p = 0.049) compared with men. Logistic regression analysis showed that women (odds ratio [OR], 1.87; 95% confidence interval [CI] 1.10-3.16), age (OR, 1.06; 95%CI 1.04-1.08) and pre-ECMO arterial lactate (OR, 1.09; 95%CI 1.04-1.16) were independent predictors of hospital mortality. No differences between female and male patients were observed for other outcomes. Among propensity score-matched pairs, one-, three-, and five-year mortality were 60.6%, 65.0%, and 65.0% among men, and 71.3%, 71.3%, and 74.0% among women, respectively (p = 0.110, adjusted hazard ratio, 1.27; 95%CI 0.96-1.66). CONCLUSIONS: In postcardiotomy VA-ECMO, female patients demonstrated higher hospital mortality than men. Morbidity and late mortality were similar between the two groups.

Factor H-related protein 1 (FHR-1) is associated with atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease (ACVD) is a lipid-driven inflammatory disease and one of the leading causes of death worldwide. Lipid deposits in the arterial wall lead to the formation of plaques that involve lipid oxidation, cellular necrosis, and complement activation, resulting in inflammation and thrombosis. The present study found that homozygous deletion of the CFHR1 gene, which encodes the plasma complement protein factor H-related protein 1 (FHR-1), was protective in two cohorts of patients with ACVD, suggesting that FHR-1 accelerates inflammation and exacerbates the disease. To test this hypothesis, FHR-1 was isolated from human plasma and was found to circulate on extracellular vesicles and to be deposited in atherosclerotic plaques. Surface-bound FHR-1 induced the expression of pro-inflammatory cytokines and tissue factor in both monocytes and neutrophils. Notably, plasma concentrations of FHR-1, but not of factor H, were significantly (p < 0.001) elevated in patients with ACVD, and correlated with the expression of the inflammation markers C-reactive protein, apolipoprotein serum amyloid protein A, and neopterin. FHR-1 expression also significantly correlated with plasma concentrations of low-density lipoprotein (LDL) (p < 0.0001) but not high-density lipoprotein (HDL). Taken together, these findings suggest that FHR-1 is associated with ACVD.

Outcome of Repeat Venoarterial Extracorporeal Membrane Oxygenation in Postcardiotomy Cardiogenic Shock.

OBJECTIVE: Data on patients requiring a second run of venoarterial extracorporeal membrane oxygenation (VA-ECMO) support in patients affected by postcardiotomy cardiogenic shock (PCS) are very limited. The authors aimed to investigate the effect of a second run of VA-ECMO on PCS patient survival. DESIGN: Retrospective analysis of an international registry. SETTING: Multicenter study, tertiary university hospitals. PARTICIPANTS: Data on adult PCS patients receiving a second run of VA-ECMO. MEASUREMENTS AND MAIN RESULTS: A total of 674 patients with a mean age of 62.9 ± 12.7 years were analyzed, and 21 (3.1%) patients had a second run of VA-ECMO. None of them required more than two VA-ECMO runs. The median duration of VA-ECMO therapy was 135 hours (interquartile range [IQR] 61-226) in patients who did not require a VA-ECMO rerun. In the rerun VA-ECMO group the median overall duration of VA-ECMO therapy was 183 hours (IQR 107-344), and the median duration of the first run was 114 hours (IQR 66-169). Nine (42.9%) of the patients who required a second run of VA-ECMO died during VA-ECMO therapy, whereas five (23.8%) survived to hospital discharge. No differences between patients treated with single or second VA-ECMO runs were observed in terms of hospital mortality and late survival. In patients requiring a second VA-ECMO run, the actuarial survival estimates at three and 12 months after VA-ECMO weaning were 23.8% ± 9.3% and 19.6% ± 6.4%, respectively. CONCLUSIONS: Repeat VA-ECMO therapy is a valid treatment strategy for PCS patients. Early and late survivals are similar between patients who have undergone a single or second run of VA-ECMO.

Mapping genetic changes in the cAMP-signaling cascade in human atria.

AIM: To obtain a quantitative expression profile of the main genes involved in the cAMP-signaling cascade in human control atria and in different cardiac pathologies. METHODS AND RESULTS: Expression of 48 target genes playing a relevant role in the cAMP-signaling cascade was assessed by RT-qPCR. 113 samples were obtained from right atrial appendages (RAA) of patients in sinus rhythm (SR) with or without atrium dilation, paroxysmal atrial fibrillation (AF), persistent AF or heart failure (HF); and left atrial appendages (LAA) from patients in SR or with AF. Our results show that right and left atrial appendages in donor hearts or from SR patients have similar expression values except for AC7 and PDE2A. Despite the enormous chamber-dependent variability in the gene-expression changes between pathologies, several distinguishable patterns could be identified. PDE8A, PI3Kγ and EPAC2 were upregulated in AF. Different phosphodiesterase (PDE) families showed specific pathology-dependent changes. CONCLUSION: By comparing mRNA-expression patterns of the cAMP-signaling cascade related genes in right and left atrial appendages of human hearts and across different pathologies, we show that 1) gene expression is not significantly affected by cardioplegic solution content, 2) it is appropriate to use SR atrial samples as controls, and 3) many genes in the cAMP-signaling cascade are affected in AF and HF but only few of them appear to be chamber (right or left) specific. TOPIC: Genetic changes in human diseased atria. TRANSLATIONAL PERSPECTIVE: The cyclic AMP signaling pathway is important for atrial function. However, expression patterns of the genes involved in the atria of healthy and diseased hearts are still unclear. We give here a general overview of how different pathologies affect the expression of key genes in the cAMP signaling pathway in human right and left atria appendages. Our study may help identifying new genes of interest as potential therapeutic targets or clinical biomarkers for these pathologies and could serve as a guide in future gene therapy studies.

Six-Month Survival After Extracorporeal Membrane Oxygenation for Severe COVID-19.

OBJECTIVES: The authors evaluated the outcome of adult patients with coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) requiring the use of extracorporeal membrane oxygenation (ECMO). DESIGN: Multicenter retrospective, observational study. SETTING: Ten tertiary referral university and community hospitals. PARTICIPANTS: Patients with confirmed severe COVID-19-related ARDS. INTERVENTIONS: Venovenous or venoarterial ECMO. MEASUREMENTS AND MAIN RESULTS: One hundred thirty-two patients (mean age 51.1 ± 9.7 years, female 17.4%) were treated with ECMO for confirmed severe COVID-19-related ARDS. Before ECMO, the mean Sequential Organ Failure Assessment score was 10.1 ± 4.4, mean pH was 7.23 ± 0.09, and mean PaO2/fraction of inspired oxygen ratio was 77 ± 50 mmHg. Venovenous ECMO was adopted in 122 patients (92.4%) and venoarterial ECMO in ten patients (7.6%) (mean duration, 14.6 ± 11.0 days). Sixty-three (47.7%) patients died on ECMO and 70 (53.0%) during the index hospitalization. Six-month all-cause mortality was 53.0%. Advanced age (per year, hazard ratio [HR] 1.026, 95% CI 1.000-1-052) and low arterial pH (per unit, HR 0.006, 95% CI 0.000-0.083) before ECMO were the only baseline variables associated with increased risk of six-month mortality. CONCLUSIONS: The present findings suggested that about half of adult patients with severe COVID-19-related ARDS can be managed successfully with ECMO with sustained results at six months. Decreased arterial pH before ECMO was associated significantly with early mortality. Therefore, the authors hypothesized that initiation of ECMO therapy before severe metabolic derangements subset may improve survival rates significantly in these patients. These results should be viewed in the light of a strict patient selection policy and may not be replicated in patients with advanced age or multiple comorbidities. CLINICAL TRIAL REGISTRATION: identifier, NCT04383678.

Factor H-related protein 1: a complement regulatory protein and guardian of necrotic-type surfaces.

Factor H-related protein 1 (FHR-1) is a member of the factor H protein family, which is involved in regulating innate immune complement reactions. Genetic modification of the encoding gene, CFHR1 on human chromosome 1, is involved in diseases such as age-related macular degeneration, C3 glomerulopathy and atypical haemolytic uraemic syndrome, indicating an important role for FHR-1 in human health. Recent research data demonstrate that FHR-1 levels increase in IgA nephropathy and anti-neutrophilic cytoplasmic autoantibodies (ANCA) vasculitis and that FHR-1 induces strong inflammation in monocytes on necrotic-type surfaces, suggesting a complement-independent role. These new results increase our knowledge about the role of this complement protein in pathology and provide a new therapeutic target, particularly in the context of inflammatory diseases induced by necrosis. This review summarizes current knowledge about FHR-1 and discusses its role in complement reactions and inflammation. LINKED ARTICLES: This article is part of a themed issue on Canonical and non-canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc.

Neurologic Injury in Patients Treated With Extracorporeal Membrane Oxygenation for Postcardiotomy Cardiogenic Shock.

OBJECTIVE: To investigate the frequency, predictors, and outcomes of neurologic injury in adults treated with postcardiotomy extracorporeal membrane oxygenation (PC-ECMO). DESIGN: A retrospective multicenter registry study. SETTING: Twenty-one European institutions where cardiac surgery is performed. PARTICIPANTS: A total of 781 adult patients who required PC-ECMO during 2010 to 2018 were divided into patients with neurologic injury (NI) and patients without neurologic injury (NNI). MEASUREMENTS AND MAIN RESULTS: Baseline and operative data, in-hospital outcomes, and long-term survival were compared between the NI and the NNI groups. Predictors of neurologic injury were identified. A subgroup analysis according to the type of neurologic injury was performed. Overall, NI occurred in 19% of patients in the overall series, but the proportion of patients with NI ranged from 0% to 65% among the centers. Ischemic stroke occurred in 84 patients and hemorrhagic stroke in 47 patients. Emergency procedure was the sole independent predictor of NI. In-hospital mortality was higher in the NI group than in the NNI group (79% v 61%, p < 0.001). The one-year survival was lower in the NI group (17%) compared with the NNI group (37%). Long-term survival did not differ between patients with ischemic stroke and those with hemorrhagic stroke. CONCLUSION: Neurologic injury during PC-ECMO is common and associated with a dismal prognosis. There is considerable interinstitutional variation in the proportion of neurologic injury in PC-ECMO-treated adults. Well-known risk factors for stroke are not associated with neurologic injury in this setting.

Duration of Venoarterial Extracorporeal Membrane Oxygenation and Mortality in Postcardiotomy Cardiogenic Shock.

OBJECTIVE: The optimal duration of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in patients affected by postcardiotomy cardiogenic shock (PCS) remains controversial. The present study was conducted to investigate the effect of VA-ECMO duration on hospital outcomes. DESIGN: Retrospective analysis of an international registry. SETTING: Multicenter study including 19 tertiary university hospitals. PARTICIPANTS: Between January 2010 and March 2018, data on PCS patients receiving VA-ECMO were retrieved from the multicenter PC-ECMO registry. INTERVENTIONS: Patients were stratified according to the following different durations of VA-ECMO therapy: ≤three days, four-to-seven days, eight-to-ten days, and >ten days. MEASUREMENTS AND MAIN RESULTS: A total of 725 patients, with a mean age of 62.9 ± 12.9 years, were included. The mean duration of VA-ECMO was 7.1 ± 6.3 days (range 0-39 d), and 39.4% of patients were supported for ≤three days, 29.1% for four-seven days, 15.3% for eight-ten days, and finally 20.7% for >ten days. A total of 391 (53.9%) patients were weaned from VA-ECMO successfully; however, 134 (34.3%) of those patients died before discharge. Multivariate logistic regression showed that prolonged duration of VA-ECMO therapy (four-seven days: adjusted rate 53.6%, odds ratio [OR] 0.28, 95% confidence interval [CI] 0.18-0.44; eight-ten days: adjusted rate 61.3%, OR 0.51, 95% CI 0.29-0.87; and >ten days: adjusted rate 59.3%, OR 0.49, 95% CI 0.31-0.81) was associated with lower risk of mortality compared with VA-ECMO lasting ≤three days (adjusted rate 78.3%). Patients requiring VA-ECMO therapy for eight-ten days (OR 1.96, 95% CI 1.15-3.33) and >10 days (OR 1.85, 95% CI 1.14-3.02) had significantly greater mortality compared with those on VA-ECMO for 4 to 7 days. CONCLUSIONS: PCS patients weaned from VA-ECMO after four-seven days of support had significantly less mortality compared with those with shorter or longer mechanical support.

Switching to Impella 5.0 decreases need for transfusion in patients undergoing temporary mechanical circulatory support.

PURPOSE: Various options of temporary mechanical circulatory support (tMCS) exist for the treatment of cardiogenic shock, however, all forms of tMCS carry a risk of complications. The aim of this study was to compare bleeding complications and thromboembolic events under extracorporeal life support + Impella 2.5/CP (ECMELLA) and isolated Impella 5.0 therapy in the same patient cohort. MATERIAL: We retrospectively analyzed data of patients who underwent ECMELLA implantation and subsequent Impella 5.0 therapy. Implantation strategy and anticoagulation protocol were comparable in both groups. RESULTS: We included 15 patients (mean age 57.2 years; 80% of male patients) who were weaned from ECMELLA undergoing subsequent Impella 5.0 implantation. Mean duration of ECMELLA and Impella 5.0 therapy (10.5 vs. 11.2 days) did not differ significantly (p = .731). The average number of transfused packed red blood cells (PRBC) and thrombocyte concentrates (TC) was significantly decreased during Impella 5.0 treatment (PRBC: 30.3 vs 12.3, p = .001; TC: 5.9 vs 2.2, p = .045). Additionally, the transfusion rates per day were significantly reduced under Impella 5.0 support. CONCLUSIONS: The need for transfusions is significantly lower in the phase of Impella 5.0 therapy compared to the initial phase on ECMELLA. Therefore, we recommend replacing ECMELLA by an Impella 5.0 device early, if possible.

Venoarterial Extracorporeal Membrane Oxygenation After Surgical Repair of Type A Aortic Dissection.

Venoarterial (VA) extracorporeal membrane oxygenation (ECMO) support for postcardiotomy cardiogenic shock (PCS) in patients undergoing surgery for acute type A aortic dissection (TAAD) is controversial and the available evidence is confined to limited case series. We aimed to evaluate the impact of this salvage therapy in this patient population. Between January 2010 and March 2018, all TAAD patients receiving VA-ECMO for PCS were retrieved from the PC-ECMO registry. Hospital mortality and other secondary outcomes were compared with PCS patients undergoing surgery for other cardiac pathologies and treated with VA-ECMO. Among the 781 patients in the PC-ECMO registry, 62 (7.9%) underwent TAAD repair and required VA-ECMO support for PCS. In-hospital mortality accounted for 46 (74.2%) patients, while 23 (37.1%) were successfully weaned from VA-ECMO. No significant differences were observed between the TAAD and non-TAAD cohorts with reference to in-hospital mortality (74.2% vs 63.4%, p = 0.089). However, patients in the TAAD group had a higher rate of neurological events (33.9% vs 17.6%, p = 0.002), but similar rates of reoperation for bleeding/tamponade (48.4% vs 41.5%, p = 0.29), transfusion of ≥10 red blood cell units (77.4% vs 69.5%, p = 0.19), new-onset dialysis (56.7% vs 53.1%, p = 0.56), and other secondary outcomes. VA-ECMO provides a valid support for patients affected by PCS after surgery for TAAD.

Multicenter study on postcardiotomy venoarterial extracorporeal membrane oxygenation.

OBJECTIVES: The aim of this study was to identify the risk factors associated with early mortality after postcardiotomy venoarterial extracorporeal membrane oxygenation. METHODS: This is an analysis of the postcardiotomy extracorporeal membrane oxygenation registry, a retrospective multicenter cohort study including 781 patients aged more than 18 years who required venoarterial extracorporeal membrane oxygenation for cardiopulmonary failure after cardiac surgery from 2010 to 2018 at 19 cardiac surgery centers. RESULTS: After a mean venoarterial extracorporeal membrane oxygenation therapy of 6.9 ± 6.2 days, hospital and 1-year mortality were 64.4% and 67.2%, respectively. Hospital mortality after venoarterial extracorporeal membrane oxygenation therapy for more than 7 days was 60.5% (P = .105). Centers that had treated more than 50 patients with postcardiotomy venoarterial extracorporeal membrane oxygenation had a significantly lower hospital mortality than lower-volume centers (60.7% vs 70.7%, adjusted odds ratio, 0.58; 95% confidence interval, 0.41-0.82). The postcardiotomy extracorporeal membrane oxygenation score was derived by assigning a weighted integer to each independent pre-venoarterial extracorporeal membrane oxygenation predictors of hospital mortality as follows: female gender (1 point), advanced age (60-69 years, 2 points; ≥70 years, 4 points), prior cardiac surgery (1 point), arterial lactate 6.0 mmol/L or greater before venoarterial extracorporeal membrane oxygenation (2 points), aortic arch surgery (4 points), and preoperative stroke/unconsciousness (5 points). The hospital mortality rates according to the postcardiotomy extracorporeal membrane oxygenation score was 0 point, 45.6%; 1 point, 40.5%; 2 points, 51.1%; 3 points, 57.8%; 4 points, 70.7%; 5 points, 68.3%; 6 points, 77.5%; and 7 points or more, 89.7% (P < .0001). CONCLUSIONS: Age, female gender, prior cardiac surgery, preoperative acute neurologic events, aortic arch surgery, and increased arterial lactate were associated with increased risk of early mortality after postcardiotomy venoarterial extracorporeal membrane oxygenation. Center experience with postcardiotomy venoarterial extracorporeal membrane oxygenation may contribute to improved results.

Peripheral versus central extracorporeal membrane oxygenation for postcardiotomy shock: Multicenter registry, systematic review, and meta-analysis.

BACKGROUND: We hypothesized that cannulation strategy in venoarterial extracorporeal membrane oxygenation (VA-ECMO) could play a crucial role in the perioperative survival of patients affected by postcardiotomy shock. METHODS: Between January 2010 and March 2018, 781 adult patients receiving VA-ECMO for postcardiotomy shock at 19 cardiac surgical centers were retrieved from the Postcardiotomy Veno-arterial Extracorporeal Membrane Oxygenation study registry. A parallel systematic review and meta-analysis (PubMed/MEDLINE, Embase, and Cochrane Library) through December 2018 was also accomplished. RESULTS: Central and peripheral VA-ECMO cannulation were performed in 245 (31.4%) and 536 (68.6%) patients, respectively. Main indications for the institution VA-ECMO were failure to wean from cardiopulmonary bypass (38%) and heart failure following cardiopulmonary bypass weaning (48%). The doubly robust analysis after inverse probability treatment weighting by propensity score demonstrated that central VA-ECMO was associated with greater hospital mortality (odds ratio 1.54; 95% confidence interval, 1.09-2.18), reoperation for bleeding/tamponade (odds ratio, 1.96; 95% confidence interval, 1.37-2.81), and transfusion of more than 9 RBC units (odds ratio, 2.42; 95% confidence interval, 1.59-3.67). The systematic review provided a total of 2491 individuals with postcardiotomy shock treated with VA-ECMO. Pooled prevalence of in-hospital/30-day mortality in overall patient population was 66.6% (95% confidence interval, 64.7-68.4%), and pooled unadjusted risk ratio analysis confirmed that patients undergoing peripheral VA-ECMO had a lower in-hospital/30-day mortality than patients undergoing central cannulation (risk ratio, 0.92; 95% confidence interval, 0.87-0.98). Adjustments for important confounders did not alter our results. CONCLUSIONS: In patients with postcardiotomy shock treated with VA-ECMO, central cannulation was associated with greater in-hospital mortality than peripheral cannulation.

Prognostic Significance of Arterial Lactate Levels at Weaning from Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: The outcome after weaning from postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) is poor. In this study, we investigated the prognostic impact of arterial lactate levels at the time of weaning from postcardiotomy VA. METHODS: This analysis included 338 patients from the multicenter PC-ECMO registry with available data on arterial lactate levels at weaning from VA-ECMO. RESULTS: Arterial lactate levels at weaning from VA-ECMO (adjusted OR 1.426, 95%CI 1.157-1.758) was an independent predictor of hospital mortality, and its best cutoff values was 1.6 mmol/L (<1.6 mmol/L, 26.2% vs. ≥ 1.6 mmol/L, 45.0%; adjusted OR 2.489, 95%CI 1.374-4.505). When 261 patients with arterial lactate at VA-ECMO weaning ≤2.0 mmol/L were analyzed, a cutoff of arterial lactate of 1.4 mmol/L for prediction of hospital mortality was identified (<1.4 mmol/L, 24.2% vs. ≥1.4 mmol/L, 38.5%, p = 0.014). Among 87 propensity score-matched pairs, hospital mortality was significantly higher in patients with arterial lactate ≥1.4 mmol/L (39.1% vs. 23.0%, p = 0.029) compared to those with lower arterial lactate. CONCLUSIONS: Increased arterial lactate levels at the time of weaning from postcardiotomy VA-ECMO increases significantly the risk of hospital mortality. Arterial lactate may be useful in guiding optimal timing of VA-ECMO weaning.

Serum FHR1 binding to necrotic-type cells activates monocytic inflammasome and marks necrotic sites in vasculopathies.

Persistent inflammation is a hallmark of many human diseases, including anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and atherosclerosis. Here, we describe a dominant trigger of inflammation: human serum factor H-related protein FHR1. In vitro, this protein selectively binds to necrotic cells via its N-terminus; in addition, it binds near necrotic glomerular sites of AAV patients and necrotic areas in atherosclerotic plaques. FHR1, but not factor H, FHR2 or FHR3 strongly induces inflammasome NLRP3 in blood-derived human monocytes, which subsequently secrete IL-1ß, TNFα, IL-18 and IL-6. FHR1 triggers the phospholipase C-pathway via the G-protein coupled receptor EMR2 independent of complement. Moreover, FHR1 concentrations of AAV patients negatively correlate with glomerular filtration rates and associate with the levels of inflammation and progressive disease. These data highlight an unexpected role for FHR1 during sterile inflammation, may explain why FHR1-deficiency protects against certain diseases, and identifies potential targets for treatment of auto-inflammatory diseases.

Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation in Patients Aged 70 Years or Older.

BACKGROUND: There is uncertainty whether venoarterial extracorporeal membrane oxygenation (VA-ECMO) should be used in older patients with cardiopulmonary failure after cardiac surgery. METHODS: This was a retrospective multicenter study of 781 patients who required postcardiotomy VA-ECMO for cardiopulmonary failure after adult cardiac surgery from 2010 to 2018 at 19 cardiac surgery centers. A parallel systematic review with meta-analysis of the literature was performed. RESULTS: The hospital mortality in the overall Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation (PC-ECMO) series was 64.4%. A total of 255 patients were 70 years old or older (32.7%), and their hospital mortality was significantly higher than in younger patients (76.1% vs 58.7%; adjusted odds ratio, 2.199; 95% confidence interval [CI], 1.536 to 3.149). Arterial lactate level greater than 6 mmol/L before starting VA-ECMO was the only predictor of hospital mortality among patients 70 years old or older in univariate analysis (82.6% vs 70.4%; P = .029). Meta-analysis of current and previous studies showed that early mortality after postcardiotomy VA-ECMO was significantly higher in patients aged 70 years or older compared with younger patients (odds ratio, 2.09; 95% CI, 1.59 to 2.75; 5 studies including 1547 patients; I2, 5.9%). The pooled early mortality rate among patients aged 70 years or older was 78.8% (95% CI, 74.1 to 83.5; 6 studies including 617 patients; I2, 41.8%). Two studies reported 1-year mortality (including hospital mortality) of 79.9% and 75.6%, respectively, in patients 70 years old or older. CONCLUSIONS: Advanced age should not be considered a contraindication for postcardiotomy VA-ECMO. However, in view of the high risk of early mortality, meaningful scrutiny is needed before using VA-ECMO after cardiac surgery in older patients.

Impella 5.0 therapy as a bridge-to-decision option for patients on extracorporeal life support with unclear neurological outcomes.

OBJECTIVES: Peripheral venoarterial extracorporeal life support (ECLS) for the treatment of cardiogenic shock has shown to improve survival but is associated with complications. However, if the patient cannot be weaned from ECLS, their therapy options are limited. Although durable left ventricular assist device implantation might be an option in such cases, an unclear neurological outcome is often a contraindication. We hypothesize that Impella 5.0 therapy provides sufficient circulatory support while avoiding ECLS-related complications, thereby allowing for an adequate evaluation of a patient's neurological state and facilitating further treatment options. METHODS: We retrospectively reviewed data from 22 ECLS patients (mean age 56.5 ± 10.7 years) with an unclear neurological status who underwent Impella 5.0 implantation between January 2016 and July 2018 in our institution. Neurological status was evaluated on a daily basis using the cerebral performance category score and the modified Rankin scale. RESULTS: Sixteen patients (72.7%) were resuscitated before ECLS implantation and 13 patients (59.1%) had acute myocardial infarction. The mean duration on ECLS before Impella 5.0 implantation was 9.3 ± 1.7 days. All patients were successfully weaned from ECLS by Impella 5.0 implantation via the axillary artery. The mean duration on Impella 5.0 was 16.3 ± 4.7 days. In surviving patients, both quantitative measurements of cerebral performance improved after 30 days compared to the baseline (P < 0.01). Six patients (27.3%) were bridged to a durable left ventricular assist device. In 9 patients (40.9%), myocardial function recovered during Impella 5.0 support and the device was successfully explanted. The 30-day survival rate was 68.2%. CONCLUSIONS: Impella 5.0 support provides a bridge-to-decision option for patients following ECLS implantation and leads to left ventricular unloading. It allows further evaluation of a patient's neurological situation and facilitates further therapy. About two-thirds of patients survived with acceptable neurological outcomes.