Evaluation of clinical outcomes in patients treated with heparin or direct thrombin inhibitors during extracorporeal membrane oxygenation: a systematic review and meta-analysis

Background: The number of patients treated with extracorporeal membrane oxygenation (ECMO) devices is increasing. Anticoagulation therapy is crucial to prevent thrombosis during ECMO therapy. Predominantly, heparin has been used as primary anticoagulant but direct thrombin inhibitors (DTI) have been established as alternatives. The aim of this systematic review and meta-analysis was to evaluate clinical outcomes in patients treated with heparin compared to different DTI during ECMO. Methods: A systematic search was conducted. Full scientific articles were sought for inclusion if heparin anticoagulation was compared to DTI (argatroban/bivalirudin) in ECMO patients. Risk of bias was assessed by Newcastle Ottawa scale. Primary endpoint was in-hospital mortality. Bleeding events, thrombotic events, hours of ECMO support, days of hospital stay, percentage of time within therapeutic range and time to therapeutic range were extracted from full texts as secondary endpoints. Results were presented as Forrest-plots. GRADE was used for confidence assessment in outcomes. Results: Systematic search identified 4.385 records, thereof 18 retrospective studies for a total of 1942 patients, complied with the predefined eligibility criteria:15 studies investigated bivalirudin and 3 studies investigated argatroban versus heparin. Risk of bias was high for most studies. In-hospital mortality, major bleeding events and pump-related thrombosis were less frequent in DTI group as compared to heparin [mortality—OR 0.69, 95% CI 0.54–0.86; major bleeding—OR 0.48, 95% CI 0.29–0.81; pump thrombosis—OR 0.55, 95% CI 0.40–0.76]. Additionally, percentage of time within therapeutic range was higher for DTI [SMD 0.54, 95% CI 0.14–0.94]. GRADE approach revealed a very low level of certainty for each outcome. Conclusion: In this meta-analysis, DTI and especially bivalirudin showed beneficial effects on clinical outcomes in ECMO patients as compared to heparin. However, due to the lack of randomized trials, certainty of evidence is low. Trial Registration: This systematic review and meta-analysis was prospectively registered at PROSPERO data base (reference number CRD42021237252). Graphical Abstract: [Figure not available: see fulltext.]

Neutrophil-lymphoycyte-ratio, platelet-lymphocyte-ratio and procalcitonin for early assessment of prognosis in patients undergoing VA-ECMO

The use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasing, but mortality remains high. Early assessment of prognosis is challenging and valid markers are lacking. This study aimed to investigate Neutrophil–Lymphocyte Ratio (NLR), Platelet-Lymphocyte-Ratio (PLR) and Procalcitonin (PCT) for early assessment of prognosis in patients undergoing VA-ECMO. This retrospective single-center cohort study included 344 consecutive patients ≥ 18 years who underwent VA-ECMO due to cardiogenic shock. Main exposures were NLR, PLR and PCT measured within 24 h after VA-ECMO initiation. The primary endpoint was all-cause in-hospital mortality. In total, 92 patients were included into final analysis (71.7% male, age 57 ± 14 years). In-hospital mortality rate was 48.9%. Receiver operating characteristics (ROC) curve revealed an area under the curve (AUC) of 0.65 [95% confidence interval (CI) 0.53–0.76] for NLR. The AUCs of PLR and PCT were 0.47 [95%CI 0.35–0.59] and 0.54 [95%CI 0.42–0.66], respectively. Binary logistic regression showed an adjusted odds ratio of 3.32 [95%CI 1.13–9.76] for NLR, 1.0 [95%CI 0.998–1.002] for PLR and 1.02 [95%CI 0.99–1.05] for PCT. NLR is independently associated with in-hospital mortality in patients undergoing VA-ECMO. However, discriminative ability is weak. PLR and PCT seem not to be suitable for this purpose

Incidence and prognosis of myocardial injury in patients with severe trauma

Purpose!#!Severe trauma can lead to end organ damages of varying severity, including myocardial injury. In the non-cardiac surgery setting, there is extensive evidence that perioperative myocardial injury is associated with increased morbidity and mortality. The impact of myocardial injury on outcome after severe trauma has not been investigated adequately yet. We hypothesized that myocardial injury is associated with increased in-hospital mortality in patients with severe trauma.!##!Materials/methods!#!This retrospective cohort study included patients ≥ 18 years with severe trauma [defined as injury severity score (ISS) ≥ 16] that were admitted to the resuscitation room of the Emergency Department of the University Hospital Duesseldorf, Germany, between 2016 and 2019. The main endpoint was in-hospital mortality. Main exposure was myocardial injury at arrival [defined as high-sensitive troponin T (hsTnT) > 14 ng/l]. For statistical analysis, receiver operating characteristic curve (ROC) and multivariate binary logistic regression were performed.!##!Results!#!Out of 368 patients, 353 were included into statistical analysis (72.5% male, age: 55 ± 21, ISS: 28 ± 12). Overall in-hospital mortality was 26.1%. Myocardial injury at presentation was detected in 149 (42.2%) patients. In-hospital mortality of patients with and without myocardial injury at presentation was 45% versus 12.3%, respectively. The area under the curve (AUC) for hsTnT and mortality was 0.76 [95% confidence interval (CI) 0.71-0.82]. The adjusted odds ratio of myocardial injury for in-hospital mortality was 2.27 ([95%CI 1.16-4.45]; p = 0.017).!##!Conclusion!#!Myocardial injury after severe trauma is common and independently associated with in-hospital mortality. Thus, hsTnT might serve as a new prognostic marker in this cohort

Fibrinogen–Albumin-Ratio is an independent predictor of thromboembolic complications in patients undergoing VA-ECMO

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) supports patients suffering from refractory cardiogenic shock. Thromboembolic complications (TeC) are common in VA-ECMO patients and are associated with increased morbidity and mortality. Valid markers to predict TeC in VA-ECMO patients are lacking. The present study investigated the predictive value of baseline Fibrinogen–Albumin-Ratio (FAR) for in-hospital TeC in patients undergoing VA-ECMO. This retrospective cohort study included patients who underwent VA-ECMO therapy due to cardiogenic shock at the University Hospital Duesseldorf, Germany between 2011 and 2018. Main exposure was baseline FAR measured at initiation of VA-ECMO therapy. The primary endpoint was the in-hospital incidence of TeC. In total, 344 patients were included into analysis (74.7% male, mean age 59 ± 14 years). The in-hospital incidence of TeC was 34%. Receiver operating characteristics (ROC) curve of FAR for in-hospital TeC revealed an area under the curve of 0.67 [95% confidence interval (CI) 0.61–0.74]. Youden index determined a cutoff of 130 for baseline FAR. Multivariate logistic regression revealed an adjusted odds-ratio of 3.72 [95% CI 2.26–6.14] for the association between FAR and TeC. Baseline FAR is independently associated with in-hospital TeC in patients undergoing VA-ECMO. Thus, FAR might contribute to the prediction of TeC in this cohort

Influence of Short and Long Hyperglycemia on Cardioprotection by Remote Ischemic Preconditioning—A Translational Approach

The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 ± 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 ± 4% (p < 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 ± 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 ± 4% (p < 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p < 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 ± 7%; p < 0.05 vs. HGl Con; HGl Con 59 ± 5%)

Influence of Short and Long Hyperglycemia on Cardioprotection by Remote Ischemic Preconditioning&mdash;A Translational Approach

The adverse impact of common diseases like diabetes mellitus and acute hyperglycemia on morbidity and mortality from myocardial infarction (MI) has been well documented over the past years of research. In the clinical setting, the relationship between blood glucose and mortality appears linear, with amplifying risk associated with increasing blood glucose levels. Further, this seems to be independent of a diagnosis of diabetes. In the experimental setting, various comorbidities seem to impact ischemic and pharmacological conditioning strategies, protecting the heart against ischemia and reperfusion injury. In this translational experimental approach from bedside to bench, we set out to determine whether acute and/or prolonged hyperglycemia have an influence on the protective effect of transferred human RIPC-plasma and, therefore, might obstruct translation into the clinical setting. Control and RIPC plasma of young healthy men were transferred to isolated hearts of young male Wistar rats in vitro. Plasma was administered before global ischemia under either short hyperglycemic (HGs Con, HGs RIPC) conditions, prolonged hyperglycemia (HGl Con, HGl RIPC), or under normoglycemia (Con, RIPC). Infarct sizes were determined by TTC staining. Control hearts showed an infarct size of 55 &plusmn; 7%. Preconditioning with transferred RIPC plasma under normoglycemia significantly reduced infarct size to 25 &plusmn; 4% (p &lt; 0.05 vs. Con). Under acute hyperglycemia, control hearts showed an infarct size of 63 &plusmn; 5%. Applying RIPC plasma under short hyperglycemic conditions led to a significant infarct size reduction of 41 &plusmn; 4% (p &lt; 0.05 vs. HGs Con). However, the cardioprotective effect of RIPC plasma under normoglycemia was significantly stronger compared with acute hyperglycemic conditions (RIPC vs. HGs RIPC; p &lt; 0.05). Prolonged hyperglycemia (HGl RIPC) completely abolished the cardioprotective effect of RIPC plasma (infarct size 60 &plusmn; 7%; p &lt; 0.05 vs. HGl Con; HGl Con 59 &plusmn; 5%)

Myocardial Injury Is Associated with the Incidence of Major Adverse Cardiac Events in Patients with Severe Trauma

Background: Severe trauma potentially results in end-organ damage such as myocardial injury. Data suggest that myocardial injury is associated with increased mortality in this cohort, but the association with the incidence of in-hospital major adverse cardiac events (MACE) remains undetermined. Methods: Retrospective cohort study including adult patients with severe trauma treated at the University Hospital Duesseldorf between January 2016 and December 2019. The main exposure was myocardial injury at presentation. Endpoints were in-hospital incidence of MACE and incidence of acute kidney injury (AKI) within 72 h. Discrimination of hsTnT for MACE and AKI was examined by the receiver operating characteristic curve (ROC) and the area under the curve (AUC). We conducted multivariate logistic regression analysis. Results: We included 353 patients in our final analysis (72.5% male (256/353), age: 55 ± 21 years). The AUC for hsTnT and MACE was 0.68 [95% confidence interval (CI): 0.59–0.78]. The AUC for hsTnT and AKI was 0.64 [95% (CI): 0.55–0.72]. The adjusted odds ratio (OR) for myocardial injury and MACE was 2.97 [95% (CI): 1.31–6.72], and it was 2.14 [95% (CI): 1.03–4.46] for myocardial injury and AKI. Conclusion: Myocardial injury at presentation in patients with severe trauma is independently associated with the incidence of in-hospital MACE and AKI

Validation of days alive and out of hospital as a new patient-centered outcome to quantify life impact after heart transplantation

The number of patients waiting for heart transplantation (HTX) is increasing. Thus, identification of outcome-relevant factors is crucial. This study aimed to identify perioperative factors associated with days alive and out of hospital (DAOH)—a patient-centered outcome to quantify life impact—after HTX. This retrospective cohort study screened 187 patients who underwent HTX at university hospital Duesseldorf, Germany from September 2010 to December 2020. The primary endpoint was DAOH at 1 year. Risk factors for mortality after HTX were assessed in univariate analysis. Variables with significant association were entered into multivariable quantile regression. In total, 175 patients were included into analysis. Median DAOH at 1 year was 295 (223–322) days. In univariate analysis the following variables were associated with reduced DAOH: recipient or donor diabetes pre-HTX, renal replacement therapy (RRT), VA-ECMO therapy, recipient body mass index, recipient estimated glomerular filtration rate (eGFR) and postoperative duration of mechanical ventilation. After adjustment, mechanical ventilation, RRT, eGFR and recipient diabetes showed significant independent association with DAOH. This study identified risk factors associated with reduced DAOH at 1-year after HTX. These findings might complement existing data for outcome of patients undergoing HTX

Impact of Cardiopulmonary Resuscitation of Donors on Days Alive and Out of Hospital after Orthotopic Heart Transplantation

Background: The number of patients waiting for heart transplantation (HTX) is increasing. Optimizing the use of all available donor hearts is crucial. While mortality seems not to be affected by donor cardiopulmonary resuscitation (CPR), the impact of donor CPR on days alive and out of hospital (DAOH) is unclear. Methods: This retrospective study included adults who underwent HTX at the University Hospital Duesseldorf, Germany from 2010&ndash;2020. Main exposure was donor-CPR. Secondary exposure was the length of CPR. The primary endpoint was DAOH at one year. Results: A total of 187 patients were screened and 171 patients remained for statistical analysis. One-year mortality was 18.7%. The median DAOH at one year was 295 days (interquartile range 206&ndash;322 days). Forty-two patients (24.6%) received donor-CPR hearts. The median length of CPR was 15 (9&ndash;21) minutes. There was no significant difference in DAOH between patients with donor-CPR hearts versus patients with no-CPR hearts (CPR: 291 days (211&ndash;318 days) vs. no-CPR: 295 days (215&ndash;324 days); p = 0.619). Multivariate linear regression revealed that there was no association between length of CPR and DAOH (unstandardized coefficients B: &minus;0.06, standard error: 0.81, 95% CI &minus;1.65&ndash;1.53, p = 0.943). Conclusions: Donor CPR status and length of CPR are not associated with reduced DAOH at one year after HTX