Dawid L. Staudacher

Triple Antithrombotic Therapy after Percutaneous Coronary Intervention (PCI) in Patients with Indication for Oral Anticoagulation: Data from a Single Center Registry.

Antithrombotic therapy consisting of a dual anti-platelet therapy (DAPT) and oral anti-coagulation (OAC) with a vitamin k antagonist is often referred to as triple therapy. This combined anticoagulation is applied in patients undergoing coronary artery stent implantation while also having an indication for OAC. Triple therapy increases the risk for bleeding events compared to either DAPT or OAC alone and thereby might be associated with adverse outcomes. Clinical data on the frequency of bleeding events in patients on triple therapy from clinical trials derives from pre-selected patients and may differ from the real world patients. We report data on patient characteristics and bleeding incidence of patients dismissed on triple therapy from a single university hospital. Within the time span from January 2000 to December 2012, we identified a total of 213 patients undergoing PCI who were prescribed a triple therapy for at least 4 weeks (representing 0.86% of all patients treated). The usage of triple therapy significantly increased over the observed time period. The average CHA2DS2-VASc Score was 3.1 ± 1.1 with an average HAS-BLED score of 2.5 ± 0.86 representing a high-risk group for thromboembolic events as well as considerable risk for bleeding events. An on-treatment bleeding incidence of 9.4% was detected, with gastrointestinal and airway bleeding being the most frequent (5.1% and 1.4%, respectively). This is consistent with data from clinical trials and confirms the high risk of bleeding in patients on DAPT plus OAC. 29.0% of all patients receiving triple therapy had an indication for OAC other than non-valvular atrial fibrillation. This substantial patient group is underrepresented by clinical trials and needs further attention.

Dual Antiplatelet Therapy (DAPT) versus No Antiplatelet Therapy and Incidence of Major Bleeding in Patients on Venoarterial Extracorporeal Membrane Oxygenation.

Aims Bleeding is a frequent complication in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). An indication for dual antiplatelet therapy due to coronary stent implantation is present in a considerable number of these patients. The objective of this retrospective study was to evaluate if dual antiplatelet therapy (DAPT) significantly increases the high intrinsic bleeding risk in patients on VA-ECMO. Methods and Results A total of 93 patients were treated with VA-ECMO between October 2010 and October 2013. Average time on VA-ECMO was 58.9 ± 1.7 hours. Dual antiplatelet therapy was given to 51.6% of all patients. Any bleeding was recorded in 60.2% of all patients. There was no difference in bleeding incidence in patients on DAPT when compared to those without any antiplatelet therapy including any bleeding (66.7% vs. 57.1%, p = 0.35), BARC3 bleeding (43.8% vs. 33.3%, p = 0.31) or pulmonary bleeding (16.7% vs. 19.0%, p = 0.77). This holds true after adjustment for confounders. Rate of transfusion of red blood cells were similar in patients with or without DAPT (35.4% vs. 28.6%, p = 0.488). Conclusions Bleeding on VA-ECMO is frequent. This registry recorded no statistical difference in bleeding in patients on dual antiplatelet therapy when compared to no antiplatelet therapy. When indicated, DAPT should not be withheld from VA ECMO patients.

Fatal air embolism as complication of percutaneous dilatational tracheostomy on venovenous extracorporeal membrane oxygenation, two case reports

BackgroundTracheostomy is recommended in case of prolonged mechanical ventilation. Therefore, most patients with an indication for venovenous extracorporeal membrane oxygenation (ECMO) will also have an indication for tracheostomy.Case presentationWe report 2 cases of fatal air embolism into the ECMO system as complication of percutaneous dilatational tracheostomy. Both patients had an AVALON ELITE® bi-caval cannula implanted draining blood from the vena cava superior and inferior.ConclusionSince there is limited safety data on this specific group of patients, a routine early dilatational tracheostomy might be associated with a significant risk.

Severe mitral regurgitation requiring ECMO therapy treated by interventional valve reconstruction using the MitraClip

Surgical repair is considered the gold standard in severe mitral valve regurgitation. Multi‐organ failure because of acute mitral insufficiency, however, can be challenging to manage as it aggravates to an inoperable state. We report the case of a 59 year old woman who presented with pulmonary oedema because of high grade mitral regurgitation. A recompensation prior to surgery using medical therapy failed and the patient developed a progressive multi‐organ failure including pulmonary, circulatory, and renal failure within days. Symptomatically, our patient could be stabilized employing an extracorporeal membrane oxygenation and an intra‐aortic balloon pump. A surgical mitral valve repair was ruled out because of the multi‐organ failure. We performed an interventional valve reconstruction using the MitraClip™ device continuing the extracorporeal membrane oxygenation and the intra‐aortic balloon counterpulsation therapy during the procedure. After clipping, multi‐organ failure regressed and the extracorporeal membrane oxygenation could be explanted at day two after intervention.

Duration of extracorporeal membrane oxygenation is a poor predictor of hospital survival.

PURPOSE Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure. In patients without the option of lung transplantation, prognostication is challenging. We hypothesized that duration of ECMO therapy is inversely correlated with the chance of recovery and therefore hospital survival. MATERIALS AND METHODS A single-center retrospective register analysis was performed. All bridge-to-recovery venovenous ECMO patients without option for lung transplantation treated between October 2010 and September 2015 were included. FINDINGS A total of 175 patients (mean age, 51.61 ± 2.11 years) were detected. Medium time on ECMO was 9.26 ± 1.91 days. Time on ECMO was not significantly shorter in survivors compared to nonsurvivors (8.23 ± 2.04 and 10.15 ± 3.07, respectively; P = .327). Rate of hospital survival and time on ECMO did not correlate (P = .103). The predictive value of ECMO duration on hospital survival was 0.503 in a receiver operating characteristic analysis. CONCLUSIONS According to our registry data, duration of ECMO therapy by itself could not predict hospital survival. Prospective studies are needed to confirm this finding.

Four situations in which ECMO might have a chance.

Dear Editor, With great interest we read the article by Matthieu Schmidt and coworkers entitled “Ten situations in which ECMO is unlikely to be successful” pointing out contraindications for extracorporeal therapies [1]. As the number of applied extracorporeal membrane oxygenation (ECMO) systems is increasing steadily [2], a discussion about contraindications is much needed. Unfortunately, evidence from randomized controlled trials to support the discussion is low. Expert opinions like the ones presented by Schmidt et al. therefore provide necessary guidance. While we completely agree on most of the points presented, we would like to comment on others.

Unprotected Left Main Percutaneous Coronary Intervention in Acute Coronary Syndromes with Extracorporeal Life Support Backup

Background. Left main PCI is superior to coronary bypass surgery in selected patients. Registry data, however, suggest significant early adverse event rates associated with unprotected left main PCI. We aimed to evaluate safety of an extracorporeal life support (ECLS) as backup system during PCI. Methods. We report a registry study of 16 high-risk patients presenting with acute coronary syndromes undergoing unprotected left main PCI with an ECLS backup. Results. Seven patients (43.8%) presented with an acute myocardial infarction while 9 patients (56.3%) had unstable angina. Unprotected left main PCI could be successfully performed in all 16 patients. Mortality or thromboembolic event rates were zero within the index hospital stay. General anesthesia was necessary only in 5 patients (31.3%). Access site bleeding requiring transfusion was encountered in 4 patients (25.0%). Three patients (18.8%) developed access site complications requiring surgical intervention. All patients were ECLS-free after 96 hours. Conclusions. Unprotected left main PCI could be safely and effectively performed after ECLS implantation as backup in acute coronary syndromes in our patient collectively. Vascular access site complications however need to be considered when applying ECLS as backup system.

Direct factor IXa inhibition with the RNA-aptamer pegnivacogin reduces platelet reactivity in vitro and residual platelet aggregation in patients with acute coronary syndromes

Background: Residual platelet reactivity is a predictor of poor prognosis in patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention. Thrombin is a major platelet activator and upon initiation of the coagulation cascade, it is subsequently produced downstream of factor IXa, which itself is known to be increased in ACS. Pegnivacogin is a novel RNA-aptamer based factor IXa inhibitor featuring a reversal agent, anivamersen. We hypothesized that pegnivacogin could reduce platelet reactivity. Methods: Whole blood samples from healthy volunteers were incubated in vitro in the presence and absence of pegnivacogin and platelet reactivity was analysed. In addition, platelet aggregometry was performed in blood samples from ACS patients in the RADAR trial featuring the intravenous administration of pegnivacogin as well as reversal by anivamersen. Results: In vitro, pegnivacogin significantly reduced adenosine diphosphate-induced CD62P-expression (100% vs. 89.79±4.04%, p=0.027, n=9) and PAC-1 binding (100% vs. 83.02±4.08%, p=0.010, n=11). Platelet aggregation was reduced (97.71±5.30% vs. 66.53±9.92%, p=0.013, n=10) as evaluated by light transmission aggregometry. In the presence of the RNA-aptamer reversal agent anivamersen, neither CD62P-expression nor platelet aggregation was attenuated. In patients with ACS treated with aspirin and clopidogrel, residual platelet aggregation was significantly reduced 20 min after intravenous bolus of 1 mg/kg pegnivacogin (100% versus 43.21±8.23%, p=0.020). Conclusion: Inhibition of factor IXa by pegnivacogin decreases platelet activation and aggregation in vitro. This effect was negated by anivamersen. In ACS patients, platelet aggregation was significantly reduced after intravenous pegnivacogin. An aptamer-based anticoagulant inhibiting factor IXa therefore might be a promising antithrombotic strategy in ACS patients.

Isoflurane or propofol sedation in patients with targeted temperature management after cardiopulmonary resuscitation: A single center study

Propose: Targeted temperature management improves outcomes in comatose patients after cardiac arrest. Short lasting sedatives might enable rapid awakening after targeted temperature management and therefore early prognostication and extubation. Aim of the present study was to compare sedation with volatile isoflurane to intravenous propofol. Materials and methods: All patients after cardiopulmonary resuscitation undergoing targeted temperature management treated between 01/2014 and 02/2017 at a single tertiary referral hospital were screened. Exclusion criteria included extracorporeal support or a survival below 48h. Results: Data on 214 patients (median age 66.1years, 62.6% shockable rhythm, survival 69.6%) are reported, 178 patients on propofol and sufentanil and 36 patients on isoflurane and sufentanil. Median time to first spontaneous breathing (9.3h vs. 9.5h, p=.373), median duration on mechanical ventilation in extubated patients (99.4h vs. 105.7h, p=.692) and median ICU stay (11.1d vs. 9.8d, p=.320) were similar in patients on propofol or isoflurane, respectively. Findings were confirmed by propensity score matching. Opioid dose was significantly lower in the isoflurane group (p<.001) while norepinephrine dose was significantly higher (p=.004). Conclusion: Isoflurane sedation is feasible on during targeted temperature management. Time to spontaneous breathing, mechanical ventilation duration or ICU stay was not reduced by isoflurane. HIGHLIGHTSIsoflurane sedation is feasible during targeted temperature management on a medical ICU.Duration of mechanical ventilation was not reduced after implementation of Isoflurane when compared to propofol sedation.Opioid dose was lower in isoflurane patients while norepinephrine dose was higher.

Development and validation of a prognostic model for survival in patients treated with venoarterial extracorporeal membrane oxygenation: the PREDICT VA-ECMO score

Aims: Several scoring systems have been introduced for prognostication after initiating venoarterial extracorporeal membrane oxygenation (VA-ECMO) therapy. However, static scores offer limited guidance once VA-ECMO is implanted, although continued allocation of healthcare resources is critical. Patients requiring continued VA-ECMO support are extremely unstable, with minimal heart function and multi-organ failure in most cases. The aim of the present study was to develop and validate a dynamic prognostic model for patients treated with VA-ECMO. Methods and results: A derivation cohort included 205 all-comers undergoing VA-ECMO implantation at a tertiary referral hospital (51% received VA-ECMO during resuscitation and 43% had severe shock). Two prediction models based on point-of-care biomarkers were developed using penalised logistic regression in an elastic net approach. A validation cohort was recruited from an independent tertiary referral hospital. Comparators for the prediction of hospital survival were the SAVE score (area under the receiver operation characteristic curve (AUC) of 0.686), the SAPS score (AUC 0.679), the APACHE score (AUC 0.662) and the SOFA score (AUC 0.732) in 6-hour survivors. The 6-hour PREDICT VA-ECMO score (based on lactate, pH and standard bicarbonate concentration) outperformed the comparator scores with an AUC of 0.823. The 12-hour PREDICT VA-ECMO integrated lactate, pH and standard bicarbonate concentration at 1 hour, 6 hours and 12 hours after ECMO insertion allowed even better prognostication (AUC 0.839). Performance of the scores in the external validation cohort was good (AUCs 0.718 for the 6-hour score and 0.735 for the 12-hour score, respectively). Conclusion: In patients requiring VA-ECMO therapy, a dynamic score using three point-of-care biomarkers predicts hospital mortality with high reliability. Furthermore, the PREDICT scores are the first scores for extracorporeal cardiopulmonary resuscitation patients.