Publications by authors named "Christoph Bode"

524 Publications

Do Inpatients Receive Risk-Based Prophylactic Treatment for Thrombotic Events?

Clin Appl Thromb Hemost 2021 Jan-Dec;27:1076029621995563

568072University Heart Center Freiburg - Bad Krozingen, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Germany.

Background: Current guidelines recommend risk-based use of prophylaxis for preventing medical inpatients from venous thromboembolism (VTE). Little is known about the current prescription practice, and even less whether differences between subspecialists like cardiologists, usually treating patients with thrombotic or thromboembolic diseases, and gastroenterologists, treating more patients with gastrointestinal bleeding complications, exist.

Methods: We performed a retrospective chart review of patients on cardiology and gastroenterology wards of our university hospital. Patients with a clear indication for anticoagulation and contraindication against antithrombotic treatment were excluded. A total of 450 patients per specialty were included. Quantitative risk assessment models were used to determine the risk of a VTE (Padua Prediction Score (PPS), IMPROVE Score) and bleeding (IMPROVE-Bleeding and HAS-BLED Score).

Results: The overall rate of VTE prophylaxis was high in both patient populations. Significant more low-risk cardiology compared to gastroenterology patients received drug-based prophylaxis. Furthermore, crucial discrepancies were found in the way individual patients would be classified based on PPS and IMPROVE Score. Finally, not the risk category but the length of hospital stay was best at predicting which patient received prophylaxis.
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http://dx.doi.org/10.1177/1076029621995563DOI Listing
April 2021

Impact of pulse pressure on clinical outcome in extracorporeal cardiopulmonary resuscitation (eCPR) patients.

Clin Res Cardiol 2021 Mar 29. Epub 2021 Mar 29.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: Hemodynamic response to successful extracorporeal cardiopulmonary resuscitation (eCPR) is not uniform. Pulse pressure (PP) as a correlate for myocardial damage or recovery from it, might be a valuable tool to estimate the outcome of these patients.

Methods: We report retrospective data of a single-centre registry of eCPR patients, treated at the Interdisciplinary Medical Intensive Care Unit at the Medical Centre, University of Freiburg, Germany, between 01/2017 and 01/2020. The association between PP of the first 10 days after eCPR and hospital survival was investigated. Moreover, patients were divided into three groups according to their PP [low (0-9 mmHg), mid (10-29 mmHg) and high (≥ 30 mmHg)] at each time point.

Results: One hundred forty-three patients (age 63 years, 74.1% male, 40% OHCA, average low flow time 49 min) were analysed. Overall hospital survival rate was 28%. A low PP both early after eCPR (after 1, 3, 6 and 12 h) and after day 1 to day 8 was associated with reduced hospital survival. At each time point (1 h to day 5) the classification of patients into a low, mid and high PP group was able to categorize the patients for a low (5-20%), moderate (20-40%) and high (50-70%) survival rate. A multivariable analysis showed that the mean PP of the first 24 h was an independent predictor for survival (p = 0.008).

Conclusion: In this analysis, PP occurred to be a valuable parameter to estimate survival and maybe support clinical decision making in the further course of patients after eCPR.
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http://dx.doi.org/10.1007/s00392-021-01838-7DOI Listing
March 2021

Catheter ablation of short-coupled variant of torsade de pointes.

Clin Res Cardiol 2021 Mar 26. Epub 2021 Mar 26.

Department of Cardiology and Angiology, Märkische Kliniken GmbH, Klinikum Luedenscheid, Luedenscheid, Germany.

Background: The short-coupled variant of torsade de pointes (sc-TdP) is a malignant arrhythmia that frequently presents with ventricular fibrillation (VF) electrical storm. Verapamil is considered the first-line therapy of sc-TdP while catheter ablation is not widely adopted. The aim of this study was to determine the origin of sc-TdP and to assess the outcome of catheter ablation using 3D-mapping.

Methods And Results: We retrospectively analyzed five patients with sc-TdP who underwent 3D-mapping and ablation of sc-TdP at five different institutions. Four patients initially presented with sudden cardiac arrest, one patient experienced recurrent syncope as the first manifestation. All patients demonstrated a monomorphic premature ventricular contraction (PVC) with late transition left bundle branch block pattern, superior axis, and a coupling interval of less than 300 ms. triggering recurrent TdP and VF. In four patients, the culprit PVC was mapped to the free wall insertion of the moderator band (MB) with a preceding Purkinje potential in two patients. Catheter ablation using 3D-mapping and intracardiac echocardiography eliminated sc-TdP in all patients, with no recurrence at mean 2.7 years (range 6 months to 8 years) of follow-up.

Conclusion: 3D-mapping and intracardiac echocardiography demonstrate that sc-TdP predominantly originates from the MB free wall insertion and its Purkinje network. Catheter ablation of the culprit PVC at the MB free wall junction leads to excellent short- and long-term results and should be considered as first-line therapy in recurrent sc-TdP or electrical storm.
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http://dx.doi.org/10.1007/s00392-021-01840-zDOI Listing
March 2021

What do we learn by repeating the ABC?

Eur Heart J 2021 Mar 26. Epub 2021 Mar 26.

University Heart Center Freiburg-Bad Krozingen, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Germany.

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http://dx.doi.org/10.1093/eurheartj/ehab146DOI Listing
March 2021

Intensive Care Resources and 60-Day Survival of Critically-Ill COVID-19 Patients.

Cureus 2021 Feb 7;13(2):e13210. Epub 2021 Feb 7.

Department of Cardiology and Angiology I (Heart Center Freiburg University - Bad Krozingen), Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, DEU.

Background: Germany reported sufficient intensive care unit (ICU) resources throughout the first wave of coronavirus disease 2019 (COVID-19). The treatment of critically ill COVID-19 patients without rationing may improve the outcome. We therefore analyzed ICU resources allocated to COVID-19 patients with respiratory failure and their outcomes.

Methods: Retrospectively, we enrolled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)-positive patients with respiratory failure from 03/08/2020 to 04/08/2020 and followed until 05/28/2020 in the university hospital of Freiburg, Germany.

Results: In the defined interval, 34 COVID-19 patients were admitted to the ICU with median age of 67±13 (31-86) years. Six of 34 (17.6%) were female. All patients suffered from moderate or severe acute respiratory distress syndrome (ARDS), 91.2% of the patients were intubated and 23.5% required extracorporeal membrane oxygenation (ECMO). Proning was performed in 67.6%, renal replacement therapy (RRT) was required in 35.3%. Ninety-six percent required more than 20 nursing hours per day. Mean ICU stay was 21±19 (1-81) days. Sixty-day survival of critically ill COVID-19 patients was 50.0% (17/34). Causes of death were multi-organ failure (52.9%), refractory ARDS (17.6%) and intracerebral hemorrhage (17.6%).

Conclusions: Treatment of critically ill COVID-19 patients is protracted and resource-intense. In a context without resources shortage, 50% of COVID-19 with respiratory failure survived up to 60 days.
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http://dx.doi.org/10.7759/cureus.13210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946605PMC
February 2021

Influence of immunosuppression in patients with severe acute respiratory distress syndrome on veno-venous extracorporeal membrane oxygenation therapy.

Artif Organs 2021 Mar 16. Epub 2021 Mar 16.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.

Background: Prognosis of patients suffering of acute respiratory distress syndrome (ARDS) is poor. This is especially true for immunosuppressed patients. If these patients should receive veno-venous extracorporeal membrane oxygenation (VV ECMO) is discussed controversial while evidence on this topic is sparse.

Methods: We report retrospective data of a single-centre registry of patients with severe ARDS requiring ECMO support between 10/2010 and 06/2019. Patients were analysed by their status of immunosuppression. ECMO weaning success and hospital survival were analysed before and after propensity score matching (PSM). Moreover, ventilator free days (VFD) were compared.

Results: A total of 288 patients were analysed (age 55years, 67%male), 88 (31%) presented with immunosuppression. Survival rates were lower in immunosuppressed patients (27%vs.53%, p<0.001 and 27%vs.48% after PSM, p=0.006). VFD (60 days) were lower for patients with immunosuppression (11.9vs.22.4, p<0.001) and immunosuppression was an independent predictor for mortality in multivariate analysis. Hospital survival was 20%, 14%, 35% and 46% for patients with oncological malignancies, solid organ transplantation, autoimmune diseases and HIV, respectively.

Conclusion: In this analysis immunosuppression was an independent predictor for mortality. However, there were major differences in the weaning and survival rates between the aetiologies of immunosuppression which should be considered in decision making.
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http://dx.doi.org/10.1111/aor.13954DOI Listing
March 2021

A DARPin targeting activated Mac-1 is a novel diagnostic tool and potential anti-inflammatory agent in myocarditis, sepsis and myocardial infarction.

Basic Res Cardiol 2021 Mar 15;116(1):17. Epub 2021 Mar 15.

Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

The monocyte β-integrin Mac-1 is crucial for leukocyte-endothelium interaction, rendering it an attractive therapeutic target for acute and chronic inflammation. Using phage display, a Designed-Ankyrin-Repeat-Protein (DARPin) was selected as a novel binding protein targeting and blocking the α I-domain, an activation-specific epitope of Mac-1. This DARPin, named F7, specifically binds to activated Mac-1 on mouse and human monocytes as determined by flow cytometry. Homology modelling and docking studies defined distinct interaction sites which were verified by mutagenesis. Intravital microscopy showed reduced leukocyte-endothelium adhesion in mice treated with this DARPin. Using mouse models of sepsis, myocarditis and ischaemia/reperfusion injury, we demonstrate therapeutic anti-inflammatory effects. Finally, the activated Mac-1-specific DARPin is established as a tool to detect monocyte activation in patients receiving extra-corporeal membrane oxygenation, as well as suffering from sepsis and ST-elevation myocardial infarction. The activated Mac-1-specific DARPin F7 binds preferentially to activated monocytes, detects inflammation in critically ill patients, and inhibits monocyte and neutrophil function as an efficient new anti-inflammatory agent.
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http://dx.doi.org/10.1007/s00395-021-00849-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960600PMC
March 2021

Hemoadsorption eliminates remdesivir from the circulation: Implications for the treatment of COVID-19.

Pharmacol Res Perspect 2021 04;9(2):e00743

Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Both antiviral treatment with remdesivir and hemoadsorption using a CytoSorb adsorption device are applied in the treatment of severe COVID-19. The CytoSorb adsorber consists of porous polymer beads that adsorb a broad range of molecules, including cytokines but also several therapeutic drugs. In this study, we evaluated whether remdesivir and its main active metabolite GS-441524 would be adsorbed by CytoSorb . Serum containing remdesivir or GS-441524 was circulated in a custom-made system containing a CytoSorb device. Concentrations of remdesivir and GS-441524 before and after the adsorber were analyzed by liquid chromatography-tandem mass spectrometry. Measurements of remdesivir in the outgoing tube after the adsorber indicated almost complete removal of remdesivir by the device. In the reservoir, concentration of remdesivir showed an exponential decay and was not longer detectable after 60 mins. GS-441524 showed a similar exponential decay but, unlike remdesivir, it reached an adsorption-desorption equilibrium at ~48 µg/L. Remdesivir and its main active metabolite GS-441524 are rapidly eliminated from the perfusate by the CytoSorb adsorber device in vitro. This should be considered in patients for whom both therapies are indicated, and simultaneous application should be avoided. In general, plasma levels of therapeutic drugs should be closely monitored under concurrent CytoSorb therapy.
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http://dx.doi.org/10.1002/prp2.743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953359PMC
April 2021

Case Report: Refusal of an Veno-Arterial Extracorporeal Membrane Oxygenation Due to Malignant Disease? - An Extremely Rare Form of Cardiac Involvement in Acute Myeloid Leukemia.

Front Med (Lausanne) 2021 23;8:584507. Epub 2021 Feb 23.

Department of Medicine I (Hematology, Oncology, and Stem-Cell Transplantation), Faculty of Medicine, Medical Center, Freiburg im Breisgau, Germany.

We report here on a 61-year-old patient with acute right heart failure of unclear etiology. Echocardiography revealed a myocardial mass infiltrating the heart, though, we assumed a cardiac lymphoma. A VA-ECMO was implanted as bridging for diagnosis and therapy. Our patient received chemotherapy, under which the tumor (of unknown etiology at this point) reached a partial remission. Nine months after first admission the patient developed acute myeloid leukemia with and mutations. Retrospective analysis of the cardiac biopsy revealed the identical mutations and matched with the diagnosis of an extremely rare primary extramedullary manifestation of an AML (myelosarcoma). The patient received induction-chemotherapy and was planned for consolidating allogeneic stem cell transplantation. From this case, we conclude that an extracorporeal therapy should be discussed in selected patients even in case of an initially fatal appearing prognosis. In selected cases, extracorporeal support can generate enough time for diagnosis and therapy. However, transparent planning, including discussion of best supportive care strategies involving the patient's family are indispensable requirements for starting ECMO in such patients.
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http://dx.doi.org/10.3389/fmed.2021.584507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940367PMC
February 2021

Medical publishing during the COVID-19 pandemic: then and now.

J Thromb Thrombolysis 2021 Mar 9. Epub 2021 Mar 9.

Heart Center, Freiburg University, Freiburg, Germany.

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http://dx.doi.org/10.1007/s11239-021-02422-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940450PMC
March 2021

Outcome Prediction in Patients with Severe COVID-19 Requiring Extracorporeal Membrane Oxygenation-A Retrospective International Multicenter Study.

Membranes (Basel) 2021 Feb 27;11(3). Epub 2021 Feb 27.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.

The role of veno-venous extracorporeal membrane oxygenation therapy (V-V ECMO) in severe COVID-19 acute respiratory distress syndrome (ARDS) is still under debate and conclusive data from large cohorts are scarce. Furthermore, criteria for the selection of patients that benefit most from this highly invasive and resource-demanding therapy are yet to be defined. In this study, we assess survival in an international multicenter cohort of COVID-19 patients treated with V-V ECMO and evaluate the performance of several clinical scores to predict 30-day survival.

Methods: This is an investigator-initiated retrospective non-interventional international multicenter registry study (NCT04405973, first registered 28 May 2020). In 127 patients treated with V-V ECMO at 15 centers in Germany, Switzerland, Italy, Belgium, and the United States, we calculated the Sequential Organ Failure Assessment (SOFA) Score, Simplified Acute Physiology Score II (SAPS II), Acute Physiology And Chronic Health Evaluation II (APACHE II) Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score, Predicting Death for Severe ARDS on V‑V ECMO (PRESERVE) Score, and 30-day survival.

Results: In our study cohort which enrolled 127 patients, overall 30-day survival was 54%. Median SOFA, SAPS II, APACHE II, RESP, and PRESERVE were 9, 36, 17, 1, and 4, respectively. The prognostic accuracy for all these scores (area under the receiver operating characteristic-AUROC) ranged between 0.548 and 0.605.

Conclusions: The use of scores for the prediction of mortality cannot be recommended for treatment decisions in severe COVID-19 ARDS undergoing V-V ECMO; nevertheless, scoring results below or above a specific cut-off value may be considered as an additional tool in the evaluation of prognosis. Survival rates in this cohort of COVID-19 patients treated with V‑V ECMO were slightly lower than those reported in non-COVID-19 ARDS patients treated with V-V ECMO.
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http://dx.doi.org/10.3390/membranes11030170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997249PMC
February 2021

Cytokine Adsorption in Severe Acute Respiratory Failure Requiring Veno-Venous Extracorporeal Membrane Oxygenation.

ASAIO J 2021 03;67(3):332-338

From the Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a last resort treatment option for patients with acute respiratory failure (acute respiratory distress syndrome [ARDS]). Cytokine adsorption has been incorporated in the management of some of these patients on an individual basis to control the imbalance of danger-associated molecular patterns and proinflammatory cytokines. However, little is known about the combination of V-V ECMO and cytokine adsorption as earlier reports contained mixed patient cohorts in terms of disease and mode of ECMO, veno-venous and veno-arterial. We here report single-center registry data of nine all-comers with severe ARDS treated with V-V ECMO and cytokine adsorption using the CytoSorb adsorber compared with a control group of nine propensity score matched patients undergoing V-V ECMO support without cytokine adsorption. Even though Respiratory ECMO Survival Prediction and PRedicting dEath for SEvere ARDS on V-V ECMO scores predicted a higher mortality in the cytokine adsorption group, mortality was numerically reduced in the patients undergoing V-V ECMO and cytokine removal compared with V-V ECMO alone. The need for fluid resuscitation and vasopressor support as well as lactate levels dropped significantly in the cytokine adsorption group within 72 hours, whereas vasopressor need and lactate levels did not decrease significantly in the control group. Therefore, our data suggest that cytokine adsorption might be beneficial in patients with severe ARDS requiring V-V ECMO support.
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http://dx.doi.org/10.1097/MAT.0000000000001302DOI Listing
March 2021

Intracerebral Hemorrhage in COVID-19 Patients with Pulmonary Failure: A Propensity Score-Matched Registry Study.

Neurocrit Care 2021 Feb 23. Epub 2021 Feb 23.

Department of Cardiology and Angiology I, Faculty of Medicine, Heart Center Freiburg University, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.

Background: Hypercoagulability in Coronavirus Disease 2019 (COVID-19) causes deep vein thrombosis and pulmonary embolism necessitating systemic anticoagulation. Case reports of intracerebral hemorrhages in ventilated COVID-19 patients warrant precaution. It is unclear, however, if COVID-19 patients with acute respiratory distress syndrome (ARDS) with or without veno-venous extracorporeal membrane oxygenation therapy (VV-ECMO) have more intracerebral hemorrhages (ICH) compared to other ARDS patients.

Methods: We conducted a retrospective observational single-center study enrolling all patients with ARDS from 01/2018 to 05/2020. PCR-positive SARS-CoV-2 patients with ARDS were allocated to the COVID-19 group. Propensity score matching was performed for age, VV-ECMO, and bleeding risk.

Results: A total of 163 patients with moderate or severe ARDS were identified, 47 (28.8%) in the COVID-19 group, and 116 (71.2%) in the non-COVID-19 group. In 63/163 cases (38.7%), VV-ECMO therapy was required. The ICU survival was 52.8%. COVID-19 patients were older, more often male, and exhibited a lower SOFA score, but the groups showed similar rates of VV-ECMO therapy. Treatments with antiplatelet agents (p = 0.043) and therapeutic anticoagulation (p = 0.028) were significantly more frequent in the COVID-19 patients. ICH was detected in 22 patients (13.5%) with no statistical difference between the groups (11.2 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.21). Propensity score matching confirmed similar rates of ICH in both groups (12.8 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.57), thus leveling out possible confounders.

Conclusions: Intracerebral hemorrhage was detected in every tenth patient with ARDS. Despite statistically higher rates of antiplatelet therapy and therapeutic anticoagulation in COVID-19 patients, we found a similar rate of ICH in patients with ARDS due to COVID-19 compared to other causes of ARDS.
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http://dx.doi.org/10.1007/s12028-021-01202-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899797PMC
February 2021

Deficiency of endothelial CD40 induces a stable plaque phenotype and limits inflammatory cell recruitment to atherosclerotic lesions in mice.

Thromb Haemost 2021 Feb 22. Epub 2021 Feb 22.

University Heart Center Freiburg-Bad Krozingen, Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Objectives: The co-stimulatory CD40L-CD40 dyad exerts a critical role in atherosclerosis by modulating leukocyte accumulation into developing atherosclerotic plaques. The requirement for cell-type specific expression of both molecules, however, remains elusive. Here, we evaluate the contribution of CD40 expressed on endothelial cells (ECs) in a mouse model of atherosclerosis. Approach & Results: Atherosclerotic plaques of Apolipoprotein E deficient (Apoe-/-) mice and humans displayed increased expression of CD40 on ECs compared to controls. To interrogate the role of CD40 on ECs in atherosclerosis, we induced EC-specific (BmxCreERT2-driven) deficiency of CD40 in Apoe-/- mice. After feeding a chow diet for 25 weeks, EC-specific deletion of CD40 (iEC-CD40) ameliorated plaque lipid deposition and lesional macrophage accumulation but increased intimal smooth muscle cell and collagen content, while atherosclerotic lesion size did not change. Leukocyte adhesion to the vessel wall was impaired in iEC-CD40-deficient mice as demonstrated by intravital microscopy. In accord, expression of vascular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the vascular endothelium declined after deletion of CD40. In vitro, antibody-mediated inhibition of human endothelial CD40 significantly abated monocyte adhesion on ECs.

Conclusions: Endothelial deficiency of CD40 in mice promotes structural features associated with a stable plaque phenotype in humans and decreases leukocyte adhesion. These results suggest that endothelial-expressed CD40 contributes to inflammatory cell migration and consecutive plaque formation in atherogenesis.
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http://dx.doi.org/10.1055/a-1397-1858DOI Listing
February 2021

Outcomes in non-ST-segment elevation myocardial infarction patients according to heart failure at admission: Insights from a large trial with systematic early invasive strategy.

Eur Heart J Acute Cardiovasc Care 2020 Oct 20. Epub 2020 Oct 20.

Université de Paris, puis APHP, Hotel Dieu, Centre de diagnostic et de Thérapeutique; French Alliance for Cardiovascular Trials (FACT); INSERM LVTS-U1148.

Background: Previous studies published before the era of systematic early invasive strategy have reported a higher mortality in non-ST-segment elevation myocardial infarction patients with heart failure. The aim of our study was to compare the clinical characteristics, outcomes and causes of death of patients according to their heart failure status at admission in a large non-ST-segment elevation myocardial infarction population with planned early invasive management.

Methods: We performed a post-hoc analysis of the Treatment of Acute Coronary Syndrome with Otamixaban randomised trial which included non-ST-segment elevation myocardial infarction patients with systematic coronary angiography within 72 h. Patients were categorised according to presence or absence of heart failure (Killip grade ≥2) at admission.

Results: A total of 13,172 patients were enrolled, of whom 944 (7.2%) had heart failure. At day 30, death occurred in 213 patients (1.6%) and cardiovascular death was the dominant cause of death in both groups ((with vs without heart failure) 78.8% vs 78.4%, p = 0.94). At six months, death occurred in 90/944 (9.5%) patients with heart failure and 258/12228 patients without heart failure (2.1%) (p < 0.001). After adjustment on Global Registry of Acute Coronary Events risk score, heart failure was an independent predictor of all-cause mortality at day 30 (odds ratio: 1.58; 95% confidence interval, 1.06-2.36, p = 0.02) and at day 180 (odds ratio: 1.77; 95% confidence interval, 1.3-2.42, p < 0.001) as well as of ischaemic complications (cardiovascular death, myocardial infarction, stent thrombosis or stroke at day 30 (odds ratio: 1.28; 95% confidence interval, 1.01-1.62, p = 0.04).

Conclusion: Non-ST-segment elevation myocardial infarction patients with heart failure at admission still have worse outcomes than those without heart failure, even with systematic early invasive strategy. Further efforts are needed to improve the prognosis of these high risk patients.
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http://dx.doi.org/10.1177/2048872619896205DOI Listing
October 2020

Bronchoalveolar Lavage and Blood Markers of Infection in Critically Ill Patients-A Single Center Registry Study.

J Clin Med 2021 Jan 29;10(3). Epub 2021 Jan 29.

Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

Microbiological sampling is an indispensable targeted antibiotic therapy for critically ill patients. Invasive respiratory sampling by bronchoalveolar lavage (BAL) can be performed to obtain samples from the lower respiratory tract. It is debated as to whether blood markers of infection can predict the outcome of BAL in a medical intensive care unit (ICU). Retrospectively, all ICU patients undergoing BAL from 2009-2018 were included. A total of 468 BAL samples from 276 patients (average age 60 years, SAPS2 47, ICU-mortality 41.7%) were analyzed. At the time of BAL, 94.4% patients were mechanically ventilated, 92.9% had suspected pneumonia, 96.2% were on antibiotic therapy and 36.3% were immunocompromised. Relevant bacteria were cultured in 114/468 (24.4%) cases of BAL. Patients with relevant bacteria in the culture had a higher ICU mortality rate (45.6 vs. 40.4%, = 0.33) and were significantly less likely to be on a steroid (36 vs. 52%, < 0.01) or antimycotic (14.9 vs. 34.2%, < 0.01), while procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) counts were similar. The area under the receiver operating curve (AUC) values for positive culture and PCT, CRP and WBC counts were low (0.53, 0.54 and 0.51, respectively). In immunocompromised patients, AUC values were higher (0.65, 0.57 and 0.61, respectively). Therefore, microbiological cultures by BAL revealed relevant bacteria in 24.4% of samples. Our data, therefore, might suggest that indication for BAL should not be based on blood markers of infection.
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http://dx.doi.org/10.3390/jcm10030486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866381PMC
January 2021

Prevalence, clinical determinants and prognostic implications of coronary procedural complications of percutaneous coronary intervention in non-ST-segment elevation myocardial infarction: Insights from the contemporary multinational TAO trial.

Arch Cardiovasc Dis 2021 Mar 29;114(3):187-196. Epub 2021 Jan 29.

FACT (an F-CRIN network), DHU-FIRE, Hôpital Bichat, AP-HP, 75018 Paris, France; Université Paris-Diderot, Sorbonne Paris Cité, 75013 Paris, France; Inserm U1148, 75877 Paris, France; NLHI, ICMS, Royal Brompton Hospital, Imperial College, SW3 6LY London, UK.

Background: Few data are available on procedural complications of percutaneous coronary intervention (PCI) in the setting of acute coronary syndrome in the contemporary era.

Aim: We sought to describe the prevalence of procedural complications of PCI in a non-ST-segment elevation acute coronary syndrome (NSTE ACS) cohort, and to identify their clinical characteristics and association with clinical outcomes.

Methods: Patients randomized in TAO (Treatment of Acute coronary syndrome with Otamixaban), an international randomized controlled trial (ClinicalTrials.gov Identifier: NCT01076764) that compared otamixaban with unfractionated heparin plus eptifibatide in patients with NSTE ACS who underwent PCI, were included in the analysis. Procedural complications were collected prospectively, categorized and adjudicated by a blinded Clinical Events Committee, with review of angiograms. A multivariable model was constructed to identify independent clinical characteristics associated with procedural complications.

Results: A total of 8656 patients with NSTE ACS who were enrolled in the TAO trial underwent PCI, and 451 (5.2%) experienced at least one complication. The most frequent complications were no/slow reflow (1.5%) and dissection with decreased flow (1.2%). Procedural complications were associated with the 7-day ischaemic outcome of death, myocardial infarction or stroke (24.2% vs. 6.0%, odds ratio 5.01, 95% confidence interval 3.96-6.33; P<0.0001) and with Thrombolysis In Myocardial Infarction major and minor bleeding (6.2% vs. 2.3%, odds ratio 2.79, 95% confidence interval 1.86-4.2; P<0.0001). Except for previous coronary artery bypass grafting, multivariable analysis did not identify preprocedural clinical predictors of complications.

Conclusions: In a contemporary NSTE ACS population, procedural complications with PCI remain frequent, are difficult to predict based on clinical characteristics, and are associated with worse ischaemic and haemorrhagic outcomes.
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http://dx.doi.org/10.1016/j.acvd.2020.09.005DOI Listing
March 2021

The Use and Outcomes of Cerebral Protection Devices for Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement in Clinical Practice.

JACC Cardiovasc Interv 2021 Jan;14(2):161-168

University Heart Center Freiburg, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Objectives: This study hypothesized that cerebral protection prevents strokes in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR) in clinical practice.

Background: Preventing strokes is an important aim in TAVR procedures. Embolic protection devices may protect against cardiac embolism during TAVR, but their use and outcomes in clinical practice remain controversial.

Methods: Isolated transfemoral TAVR procedures performed in Germany with or without cerebral protection devices were extracted from a comprehensive nationwide billing dataset.

Results: A total of 41,654 TAVR procedures performed between 2015 and 2017 were analyzed. The overall share of procedures incorporating cerebral protection devices was 3.8%. Patients receiving cerebral protection devices were at increased operative risk (European System for Cardiac Operative Risk Evaluation score 13.8 vs. 14.7; p < 0.001) but of lower age (81.1 vs. 80.6 years; p = 0.001). To compare outcomes that may be related to the use of cerebral protection devices, a propensity score comparison was performed. The use of a cerebral protection device did not reduce the risk for stroke (adjusted risk difference [aRD]: +0.88%; 95% confidence interval [CI]: -0.07% to 1.83%; p = 0.069) or the risk for developing delirium (aRD: +1.31%; 95% CI: -0.28% to 2.89%; p = 0.106) as a sign of acute brain failure. Although brain damage could not be prevented, in-hospital mortality was lower in the group receiving a cerebral protection device (aRD: -0.76%; 95% CI: -1.46% to -0.06%; p = 0.034).

Conclusions: In this large national database, cerebral embolic protection devices were infrequently used during TAVR procedures. Device use was associated with lower mortality but not a reduction in stroke or delirium. Future studies are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.jcin.2020.09.047DOI Listing
January 2021

Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation: protocol for a randomised, controlled, open-label intervention, multicentre trial.

BMJ Open 2021 01 17;11(1):e043345. Epub 2021 Jan 17.

Department of Medicine III (Interdisciplinary Medical Intensive Care), University of Freiburg, Faculty of Medicine, Freiburg, Baden-Württemberg, Germany

Introduction: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a last resort treatment option in patients with severe COVID-19 related acute respiratory distress syndrome (ARDS). Mortality in these critically ill patients is high. Elevated interleukin-6 (IL-6) levels in these severe courses are associated with poor outcome. Extracorporeal cytokine adsorption is an approach to lower elevated IL-6 levels. However, there is no randomised controlled data on the efficacy of cytokine adsorption and its effect on patient outcome in severe COVID-19 related ARDS requiring V-V ECMO support.

Methods And Analysis: We here report the protocol of a 1:1 randomised, controlled, parallel group, open-label intervention, superiority multicentre trial to evaluate the effect of extracorporeal cytokine adsorption using the CytoSorb device in severe COVID-19 related ARDS treated with V-V ECMO. We hypothesise that extracorporeal cytokine adsorption in these patients is effectively reducing IL-6 levels by 75% or more after 72 hours as compared with the baseline measurement and also reducing time to successful V-V ECMO explantation. We plan to include a total of 80 patients at nine centres in Germany.

Ethics And Dissemination: The protocol of this study was approved by the ethical committee of the University of Freiburg as the leading institution (EK 285/20). Additional votes will be obtained at all participating centres.

Trial Registration Numbers: NCT04385771 and DRKS 00021248.
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http://dx.doi.org/10.1136/bmjopen-2020-043345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813398PMC
January 2021

Hospital networks and patient transport capacity during the COVID-19 pandemic when intensive care resources become scarce.

Crit Care 2021 01 12;25(1):28. Epub 2021 Jan 12.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

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http://dx.doi.org/10.1186/s13054-021-03462-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803004PMC
January 2021

Sex Differences in Ischemic and Bleeding Outcomes in Patients With Non-ST-Segment-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Insights From the TAO Trial.

Circ Cardiovasc Interv 2021 Jan 12;14(1):e009759. Epub 2021 Jan 12.

Université de Paris, AP-HP, FACT, FHU APOLLO, Hôpital Bichat, Inserm U-1148, Paris, France (G.D., Y.E., P.G.S.).

Background: Previous studies have observed poorer outcomes in females with myocardial infarction, but older age and lower use of percutaneous coronary intervention in females are factors that potentially explain the worse outcome. This study sought to determine if female sex is an independent factor of ischemic and bleeding outcomes in non-ST-segment-elevation acute coronary syndrome treated with a systematic invasive approach.

Methods: The TAO trial (Treatment of Acute Coronary Syndrome With Otamixaban) randomized patients with non-ST-segment-elevation acute coronary syndrome treated invasively to heparin plus eptifibatide versus otamixaban. In this post hoc analysis, the primary ischemic end point (all-cause death, myocardial infarction within 180 days) and the primary safety end point (Thrombolysis in Myocardial Infarction major or minor bleeding within 30 days) were analyzed according to sex.

Results: Of 13 229 randomized patients, 3980 (30.1%) were females and 9249 (69.9%) were males. Females were older (64.8±11.0 versus 60.7±11.1 years), had more comorbidities, received less peri-procedural antithrombotic therapy, and underwent less frequently revascularization. Overall, females experienced a higher risk of ischemic (10.2% versus 9.1%; odds ratio [OR], 1.15 [1.01-1.30]) and bleeding events (4.2% versus 3.4%; OR, 1.23 [1.02-1.49]) than males. After multivariate analysis, the risk of ischemic outcomes (OR, 1.04 [0.90-1.19]), death (OR, 1.00 [0.75-1.23]), or bleeding (OR, 1.05 [0.85-1.28]), were similar between females and males. Only, noncoronary artery bypass graft related Thrombolysis in Myocardial Infarction major bleeding were increased in females (OR, 1.69 [1.11-2.56]).

Conclusions: In patients with non-ST-segment-elevation acute coronary syndrome with systematic invasive management, ischemic outcomes, bleeding events, and mortality were higher in females. After multivariate analyses, female sex was not an independent predictor of ischemic and bleeding events although noncoronary artery bypass graft related Thrombolysis in Myocardial Infarction major bleeding was higher in females. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01076764.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.009759DOI Listing
January 2021

Extracorporeal organ support in the treatment of coronavirus disease 2019? Yes, but with caution.

Artif Organs 2021 Jan 7. Epub 2021 Jan 7.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany.

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http://dx.doi.org/10.1111/aor.13885DOI Listing
January 2021

Time course of red cell volume and plasma volume over six months in compensated chronic heart failure.

ESC Heart Fail 2021 Apr 5;8(2):1696-1699. Epub 2021 Jan 5.

Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Hugstetter Straße 55, Freiburg, 79106, Germany.

Background: In patients with chronic heart failure (CHF), volume overload is usually described as an expansion of plasma volume (PV). Additional red cell volume (RCV) expansion also occurs in a relevant fraction of compensated CHF patients. So far, little is known about the stability of these vascular volumes and possible volume excess in compensated CHF patients over time.

Methods And Results: This study aims at quantification of blood volume and its components, RCV and PV (raw values and adjusted for sex and anthropometric characteristics, expressed as per cent of the expected normal value), using an abbreviated carbon monoxide (CO) rebreathing method (aCORM) in 14 patients (two women) with systolic CHF at baseline and at a follow-up visit after approximately 6 months. While a vast heterogeneity was observed concerning RCV (82% to 134% of normalized alues) and PV (72% to 131% of normalized values), the vascular volumes showed a mean change of 1.2% and -1.3% after a mean follow-up of 183 days.

Conclusions: The vascular volumes including individual volume excess appear to be stable in compensated CHF patients. The reason for this individual volume response concerning both RCV and PV in CHF remains unclear and deserves further clarification.
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http://dx.doi.org/10.1002/ehf2.13179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006671PMC
April 2021

Two siblings with early repolarization syndrome: clinical and genetic characterization by whole-exome sequencing.

Europace 2020 Dec 16. Epub 2020 Dec 16.

Department of Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Heart Center, Amsterdam, The Netherlands.

Aims : The early repolarization syndrome (ERS) can cause ventricular fibrillation (VF) and sudden death in young, otherwise healthy individuals. There are limited data suggesting that ERS might be heritable. The aim of this study was to characterize the clinical phenotype and to identify a causal variant in an affected family using an exome-sequencing approach.

Methods And Results : Early repolarization syndrome was diagnosed according to the recently proposed Shanghai ERS Score. After sequencing of known ERS candidate genes, whole-exome sequencing (WES) was performed. The index patient (23 years, female) showed a dynamic inferolateral early repolarization (ER) pattern and electrical storm with intractable VF. Isoproterenol enabled successful termination of electrical storm with no recurrence on hydroquinidine therapy during 33 months of follow-up. The index patient's brother (25 years) had a persistent inferior ER pattern with malignant features and a history of syncope. Both parents were asymptomatic and showed no ER pattern. While there was no pathogenic variant in candidate genes, WES detected a novel missense variant affecting a highly conserved residue (p. H2245R) in the ANK3 gene encoding Ankyrin-G in the two siblings and the father.

Conclusion : We identified two siblings with a malignant ERS phenotype sharing a novel ANK3 variant. A potentially pathogenic role of the novel ANK3 variant is suggested by the direct interaction of Ankyrin-G with the cardiac sodium channel, however, more patients with ANK3 variants and ERS would be required to establish ANK3 as novel ERS susceptibility gene. Our study provides additional evidence that ERS might be a heritable condition.
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http://dx.doi.org/10.1093/europace/euaa357DOI Listing
December 2020

Extracorporeal Membrane Oxygenation and Inflammation in COVID-19.

ASAIO J 2021 02;67(2):e72-e73

Department of Medicine III (Interdisciplinary Medical Intensive Care), Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany., Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany.

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http://dx.doi.org/10.1097/MAT.0000000000001328DOI Listing
February 2021

Transcatheter valve-in-valve implantation in degenerated aortic bioprostheses: are patients with small surgical bioprostheses at higher risk for unfavourable mid-term outcomes?

Ann Cardiothorac Surg 2020 Nov;9(6):478-486

Department of Cardiovascular Surgery, University Heart Center Freiburg · Bad Krozingen, Bad Krozingen, Germany.

Background: To examine outcomes of valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) according to the inner diameter (ID) of the degenerated aortic valve bioprosthesis.

Methods: We analyzed survival, stroke, permanent pacemaker (PPM) implantation, paravalvular (PV) leakage, acute kidney injury and vascular complications in fifty-nine patients during a ten-year period. Patients were stratified according to the ID of the indwelling degenerated biological aortic valve (true ID ≤ and >20 mm). Differences in post-procedural transvalvular gradients and hospital re-admissions were analyzed.

Results: The median age of the small diameter group and large diameter group was eighty-one and eighty years, respectively. Median logistic EuroSCORE I was 23.9% and 26.2% and median Society of Thoracic Surgeons (STS) score was 5.7% and 7.8% for the small and large groups, respectively. Survival, stroke, PPM implantation, PV leakage, acute kidney injury and vascular complications did not reach any statistically significant difference between both groups. Postprocedural transvalvular gradients differed significantly according to the true ID of the degenerated bioprosthetic valve and consequently of the respective TAVI valve. There was a significant difference with regard to hospital readmissions according to the true ID.

Conclusions: TAVI ViV implantation for aortic bioprostheses with small true IDs of ≤20 mm is associated with comparable mid-term mortality and periprocedural stroke rate compared to implantation into larger bioprostheses. However, the periprocedural and mid-term transvalvular gradients, as well as hospital re-admission rates are significantly higher in the small diameter group.
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http://dx.doi.org/10.21037/acs-2020-av-fs-0124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724066PMC
November 2020

Inhibition of macrophage proliferation dominates plaque regression in response to cholesterol lowering.

Basic Res Cardiol 2020 12 9;115(6):78. Epub 2020 Dec 9.

Department of Cardiology and Angiology I, University Heart Center Freiburg-Bad Krozingen and Faculty of Medicine, University of Freiburg, 55 Hugstetter St, 79106, Freiburg, Germany.

Statins induce plaque regression characterized by reduced macrophage content in humans, but the underlying mechanisms remain speculative. Studying the translational APOE*3-Leiden.CETP mouse model with a humanized lipoprotein metabolism, we find that systemic cholesterol lowering by oral atorvastatin or dietary restriction inhibits monocyte infiltration, and reverses macrophage accumulation in atherosclerotic plaques. Contrary to current believes, none of (1) reduced monocyte influx (studied by cell fate mapping in thorax-shielded irradiation bone marrow chimeras), (2) enhanced macrophage egress (studied by fluorescent bead labeling and transfer), or (3) atorvastatin accumulation in murine or human plaque (assessed by mass spectrometry) could adequately account for the observed loss in macrophage content in plaques that undergo phenotypic regression. Instead, suppression of local proliferation of macrophages dominates phenotypic plaque regression in response to cholesterol lowering: the lower the levels of serum LDL-cholesterol and lipid contents in murine aortic and human carotid artery plaques, the lower the rates of in situ macrophage proliferation. Our study identifies macrophage proliferation as the predominant turnover determinant and an attractive target for inducing plaque regression.
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http://dx.doi.org/10.1007/s00395-020-00838-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725697PMC
December 2020

Relationship between baseline cardiac biomarkers and cardiovascular death or hospitalization for heart failure with and without sodium-glucose co-transporter 2 inhibitor therapy in DECLARE-TIMI 58.

Eur J Heart Fail 2020 Dec 2. Epub 2020 Dec 2.

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Aims: Dapagliflozin reduced the risk of the composite of cardiovascular (CV) death or hospitalization for heart failure (HHF) in patients with type 2 diabetes mellitus in DECLARE-TIMI 58. We hypothesized that baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) levels would help identify patients who are at higher baseline risk and we describe the treatment effects of dapagliflozin in patients according to their baseline NT-proBNP and hsTnT levels.

Methods And Results: This was a pre-specified biomarker study from DECLARE-TIMI 58, a randomized, double-blind, placebo-controlled CV outcomes trial of dapagliflozin. Baseline NT-proBNP and hsTnT levels were measured in the TIMI Clinical Trials Laboratory in 14 565 patients. Among the included patients, 9143 patients (62.8%) were male, 1464 (10.1%) had a history of heart failure and the mean age was 63.9 years. The median baseline NT-proBNP and hsTnT levels were 75 pg/mL [interquartile range (IQR) 35-165] and 10.2 pg/mL (IQR 6.9-15.5), respectively. Patients with higher NT-proBNP and hsTnT quartiles had higher rates of CV death/HHF (Q4 vs. Q1: NT-proBNP: 4-year Kaplan-Meier event rates 13.7% vs. 1.0%; hsTnT: 11.8% vs. 1.4%; P-trend <0.001). Dapagliflozin consistently reduced the relative risk of CV death/HHF regardless of baseline NT-proBNP (P-interaction 0.72) or hsTnT quartiles (P-interaction 0.93). Given their higher baseline risk, patients with NT-proBNP and/or hsTnT levels above the median derived larger absolute risk reductions with dapagliflozin (NT-proBNP 1.9% vs. 0%, P-interaction 0.010; hsTnT 1.8% vs. 0.1%, P-interaction 0.026).

Conclusion: Patients with type 2 diabetes mellitus and higher NT-proBNP or hsTnT levels are at increased risk of CV death and HHF. Dapagliflozin reduced the relative risk of CV death/HHF irrespective of NT-proBNP and hsTnT levels, with greater absolute risk reductions seen in patients with higher baseline biomarker levels.
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http://dx.doi.org/10.1002/ejhf.2073DOI Listing
December 2020

Cardiogenic shock: incidence, survival and mechanical circulatory support usage 2007-2017-insights from a national registry.

Clin Res Cardiol 2020 Nov 30. Epub 2020 Nov 30.

Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.

Background: A central element in the management of cardiogenic shock (CS) comprises mechanical circulatory support (MCS) systems to maintain cardiac output (CO). This study aims to quantify incidence, outcome and influence of MCS in CS over the last decade.

Methods: All patients hospitalized with CS in a tertiary university hospital in Germany between 2007 and 2017 were identified utilizing the international coding system ICD-10 with code R57.0. Application of MCS was identified via German procedure classification codes (OPS).

Results: 383,983 cases of cardiogenic shock were reported from 2007 to 2017. Patients had a mean age of 71 years and 38.5% were female. The incidence of CS rose by 65.6% from 26,828 cases in 2007 (33.1 per 100,000 person-years, hospital survival 39.2%) to 44,425 cases in 2017 (53.7 per 100,000 person-years, survival 41.2%). In 2007, 16.0% of patients with CS received MCS (4.6 per 100,000 person-years, survival 46.6%), dropping to 13.9% in 2017 (6.6 per 100,000 person-years, survival 38.6%). Type of MCS changed over the years, with decreasing use of the intra-aortic balloon pump (IABP), an increase in extracorporeal membrane oxygenation (VA-ECMO) and percutaneous ventricular assist device (pVAD) usage. Significant differences regarding in-hospital survival were observed between the devices (survival: overall: 40.2%; medical treatment = 39.5%; IABP = 49.5%; pVAD = 36.2%; VA-ECMO = 30.5%; p < 0.001).

Conclusions: The incidence of CS is increasing, but hospital survival remains low. MCS was used in a minority of patients, and the percentage of MCS usage in CS has decreased. The use rates of the competing devices change over time.
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http://dx.doi.org/10.1007/s00392-020-01781-zDOI Listing
November 2020