Publications by authors named "Evangelos Giannitsis"

319 Publications

Presence of contractile impairment appears crucial for structural remodeling in idiopathic left bundle-branch block.

J Cardiovasc Magn Reson 2021 Apr 1;23(1):39. Epub 2021 Apr 1.

Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Background: To differentiate effects of ventricular asynchrony from an underlying hypocontractile cardiomyopathy this study aimed to enhance the understanding of functional impairment and structural remodeling in idiopathic left bundle-branch block (LBBB). We hypothesize, that functional asynchrony with septal flash volume effects alone might not entirely explain the degree of functional impairment. Hence, we suggest the presence of a superimposed contractile cardiomyopathy.

Methods: In this retrospective study, 53 patients with idiopathic LBBB were identified and matched to controls with and without cardiovascular risk factors. Cardiovascular magnetic resonance (CMR) was used to evaluate cardiac function, volumes and myocardial fibrosis using native T1 mapping and late gadolinium enhancement (LGE). Septal flash volume was assessed by CMR volumetric measurements and allowed to stratify patients with systolic dysfunction solely due to isolated ventricular asynchrony or superimposed contractile impairment.

Results: Reduced systolic LV-function, increased LV-volumes and septal myocardial fibrosis were found in patients with idiopathic LBBB compared to healthy controls. LV-volumes increased and systolic LV-function declined with prolonged QRS duration. Fibrosis was typically located at the right ventricular insertion points. Subgroups with superimposed contractile impairment appeared with pronounced LV dilation and increased fibrotic remodeling compared to individuals with isolated ventricular asynchrony.

Conclusions: The presence of superimposed contractile impairment in idiopathic LBBB is crucial to identify patients with enhanced structural remodeling. This finding suggests an underlying cardiomyopathy. Future studies are needed to assess a possible prognostic impact of this entity and the development of heart failure.

Trial Registration: This study was retrospectively registered.
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http://dx.doi.org/10.1186/s12968-021-00731-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015193PMC
April 2021

Research Article: Management of Pulmonary Embolism: Results from the German Chest Pain Unit Registry.

Cardiology 2021 Mar 10:1-7. Epub 2021 Mar 10.

Department of Cardiology, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany.

Introduction: Since 2008, specialized chest pain units (CPUs) were implemented across Germany ensuring structured diagnostics in acute chest pain. This study aims to analyze the management of pulmonary embolism (PE) patients in such certified CPUs.

Methods: Data were retrieved from 13,902 patients enrolled in the German CPU registry and analyzed for the diagnosis of PE including patient characteristics, critical time intervals, diagnostic workup, treatment, and prognosis. PE patients were compared to the overall CPU patient cohort. Only patients with a complete 3-month follow-up were included.

Results: Overall, 1.1% of all CPU patients were diagnosed with PE. Chest pain and dyspnea were the leading symptoms. Patients with PE were older, presented with higher heart rates, and more frequently exhibited signs of heart failure, despite a normal left ventricular function. PE patients showed significantly longer time delays between symptom onset and the first medical contact, while PE patients with chest pain presented earlier than PE patients with dyspnea only. Whereas more PE patients had to be transferred to the intensive care unit, in-CPU mortality and event rates over 3 months were low.

Discussion/conclusion: This study suggests a certain risk for underdiagnosis and consecutive potential undertreatment of PE patients in German Cardiac Society (GCS)-certified CPUs, which is thought to result from an anticipated focus on patients with acute coronary syndrome (ACS). Public awareness for PE beyond chest pain should be improved. Certified CPUs should be urged to implement strategic pathways for a better simultaneous diagnostic workup of differential diagnosis beyond ACS.
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http://dx.doi.org/10.1159/000513695DOI Listing
March 2021

Cardiovascular biomarkers in patients with COVID-19.

Eur Heart J Acute Cardiovasc Care 2021 Feb 28. Epub 2021 Feb 28.

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

The coronavirus disease 2019 (COVID-19) pandemic has increased awareness that severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) may have profound effects on the cardiovascular system. COVID-19 often affects patients with pre-existing cardiac disease, and may trigger acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), acute myocardial infarction (AMI), and acute heart failure (AHF). However, as COVID-19 is primarily a respiratory infectious disease, there remain substantial uncertainty and controversy whether and how cardiovascular biomarkers should be used in patients with suspected COVID-19. To help clinicians understand the possible value as well as the most appropriate interpretation of cardiovascular biomarkers in COVID-19, it is important to highlight that recent findings regarding the prognostic role of cardiovascular biomarkers in patients hospitalized with COVID-19 are similar to those obtained in studies for pneumonia and ARDS in general. Cardiovascular biomarkers reflecting pathophysiological processes involved in COVID-19/pneumonia and its complications have a role evaluating disease severity, cardiac involvement, and risk of death in COVID-19 as well as in pneumonias caused by other pathogens. First, cardiomyocyte injury, as quantified by cardiac troponin concentrations, and haemodynamic cardiac stress, as quantified by natriuretic peptide concentrations, may occur in COVID-19 as in other pneumonias. The level of those biomarkers correlates with disease severity and mortality. Interpretation of cardiac troponin and natriuretic peptide concentrations as quantitative variables may aid in risk stratification in COVID-19/pneumonia and also will ensure that these biomarkers maintain high diagnostic accuracy for AMI and AHF. Second, activated coagulation as quantified by D-dimers seems more prominent in COVID-19 as in other pneumonias. Due to the central role of endothelitis and VTE in COVID-19, serial measurements of D-dimers may help physicians in the selection of patients for VTE imaging and the intensification of the level of anticoagulation from prophylactic to slightly higher or even therapeutic doses.
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http://dx.doi.org/10.1093/ehjacc/zuab009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989520PMC
February 2021

Critical appraisal of the 2020 ESC guideline recommendations on diagnosis and risk assessment in patients with suspected non-ST-segment elevation acute coronary syndrome.

Clin Res Cardiol 2021 Feb 26. Epub 2021 Feb 26.

3rd Department of Internal Medicine, Cardiology and Intensive Care Medicine, Wilhelminenhospital, Vienna, Austria.

Multiple new recommendations have been introduced in the 2020 ESC guidelines for the management of acute coronary syndromes with a focus on diagnosis, prognosis, and management of patients presenting without persistent ST-segment elevation. Most recommendations are supported by high-quality scientific evidence. The guidelines provide solutions to overcome obstacles presumed to complicate a convenient interpretation of troponin results such as age-, or sex-specific cutoffs, and to give practical advice to overcome delays of laboratory reporting. However, in some areas, scientific support is less well documented or even missing, and other areas are covered rather by expert opinion or subjective recommendations. We aim to provide a critical appraisal on several recommendations, mainly related to the diagnostic and prognostic assessment, highlighting the discrepancies between Guideline recommendations and the existing scientific evidence.
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http://dx.doi.org/10.1007/s00392-021-01821-2DOI Listing
February 2021

Biomarkers of coagulation and fibrinolysis in acute myocardial infarction: a joint position paper of the Association for Acute CardioVascular Care and the European Society of Cardiology Working Group on Thrombosis.

Eur Heart J Acute Cardiovasc Care 2020 Nov 7. Epub 2020 Nov 7.

Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Blvd. 161, 8200 Aarhus N, Denmark.

The formation of a thrombus in an epicardial artery may result in an acute myocardial infarction (AMI). Despite major advances in acute treatment using network approaches to allocate patients to timely reperfusion and optimal antithrombotic treatment, patients remain at high risk for thrombotic complications. Ongoing activation of the coagulation system as well as thrombin-mediated platelet activation may both play a crucial role in this context. Whether measurement of circulating biomarkers of coagulation and fibrinolysis could be useful for risk stratification in secondary prevention is currently not fully understood. In addition, measurement of such biomarkers could be helpful to identify thrombus formation as the leading mechanism for AMI. The introduction of biomarkers of myocardial injury such as high-sensitivity cardiac troponins made rule-out of AMI even more precise. However, elevated markers of myocardial injury cannot provide proof of a type 1 AMI, let alone thrombus formation. The combined measurement of markers of myocardial injury with biomarkers reflecting ongoing thrombus formation might be helpful for the fast and correct diagnosis of an atherothrombotic type 1 AMI. This position paper gives an overview of the current knowledge and possible role of biomarkers of coagulation and fibrinolysis for the diagnosis of AMI, risk stratification, and individualized treatment strategies in patients with AMI.
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http://dx.doi.org/10.1093/ehjacc/zuaa025DOI Listing
November 2020

Diagnostic performance of D-dimer in predicting venous thromboembolism and acute aortic dissection.

Eur Heart J Acute Cardiovasc Care 2020 Mar 18. Epub 2020 Mar 18.

Background: D-dimer is elevated in a variety of conditions. The purpose of this study was to assess the positive predictive value of D-dimer to rule in patients with confirmed pulmonary embolism, deep vein thrombosis, acute aortic dissection or thrombosis of the upper extremity in comparison to patients with elevated D-dimer for other reasons.

Methods And Results: We studied 1334 patients presenting to the emergency department with pulmonary embolism (n=193), deep vein thrombosis (n=73), acute aortic dissection (n=22), thrombosis of the upper extremity (n=8) and 1038 controls. The positive predictive value was increased with higher D-dimer concentrations improving the ability to identify diseases with high thrombus burden. Patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity showed a maximum positive predictive value of 85.2% at a D-dimer level of 7.8 mg/L (95% confidence interval (CI) 78.1 to 90.4). The maximum positive predictive value was lower in cancer patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity, reaching 68.9% at a D-dimer level of 7.5 mg/L (95% CI 57.4 to 78.4). The positive likelihood ratio was very consistent with the positive predictive value. Using a cut-off level of 0.5 mg/L, D-dimer showed a high sensitivity of at least 93%, but a very low specificity of nearly 0%. Conversely, an optimised cut-off value of 4.6 mg/L increased specificity to 95% for the detection of life-threatening venous thromboembolism, acute aortic dissection or thrombosis of the upper extremity at the costs of moderate sensitivities (58% for pulmonary embolism, 41% for deep vein thrombosis, 65% for pulmonary embolism with co-existent deep vein thrombosis, 50% for acute aortic dissection and 13% for thrombosis of the upper extremity). Using the same cut-off in cancer patients, higher values were observed for sensitivity at a specificity level of more than 95%. The area under the curve for the discrimination of venous thromboembolism/acute aortic dissection/thrombosis of the upper extremity from controls was significantly higher in cancer versus non-cancer patients (area under the curve 0.905 in cancer patients, 95% CI 0.89 to 0.92, vs. area under the curve 0.857 in non-cancer patients, 95% CI 0.84 to 0.88; P=0.0349).

Conclusion: D-dimers are useful not only to rule out but also to rule in venous thromboembolism and acute aortic dissection with an at least moderate discriminatory ability, both in patients with and without cancer.
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http://dx.doi.org/10.1177/2048872620907322DOI Listing
March 2020

Validation of two severity scores as predictors for outcome in Coronavirus Disease 2019 (COVID-19).

PLoS One 2021 19;16(2):e0247488. Epub 2021 Feb 19.

Department of Internal Medicine III, Cardiology, University of Heidelberg, Heidelberg, Germany.

Background: An established objective and standardized reporting of clinical severity and disease progression in COVID-19 is still not established. We validated and compared the usefulness of two classification systems reported earlier-a severity grading proposed by Siddiqi and a system from the National Australian COVID-19 guideline. Both had not been validated externally and were now tested for their ability to predict complications.

Methods: In this retrospective, single-centre observational study, patients hospitalized with confirmed COVID-19 across all severity stages were enrolled. The clinical severity was graded at admission and during hospitalization. Multivariate Cox regression was used to identify independent risk factors for mortality, a composite primary (mortality, incident acute respiratory distress syndrome, incident mechanical ventilation), a secondary endpoint (mortality, incident acute myocardial injury, incident venous thrombosis, pulmonary embolism or stroke) and progression of severity grades.

Results: Of 109 patients 17 died, 31 and 48 developed the primary and secondary endpoint, respectively. Worsening of the severity grade by at least one stage occurred in 27 and 28 patients, respectively. Siddiqi and Australian classification were identified as independent predictors for the primary endpoint (adjusted hazard ratio (aHR) 2.30, p<0.001 and aHR 2.08, p<0.001), for the secondary endpoint (aHR 2.12, p<0.001 and aHR 1.79, p<0.001) and mortality (aHR 2.30, p = 0.071 and aHR 1.98, p = 0.017). Both classification systems showed very good agreement regarding initial grading and good agreement regarding progression of severity stages.

Conclusions: Standardized and objective severity grading is useful to unequivocally stratify patients presenting with COVID-19 for their individual risk of complications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247488PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895342PMC
March 2021

Diagnostic value of circulating microRNAs compared to high-sensitivity troponin T for the detection of non-ST-segment elevation myocardial infarction.

Eur Heart J Acute Cardiovasc Care 2021 Jan 4. Epub 2021 Jan 4.

Zentrum für Innere Medizin, Klinik für Kardiologie, Angiologie und Pneumologie, Universitätsklinikum Heidelberg, Germany.

Aims: To assess the diagnostic value of microRNAs (miRNAs) for the detection of non-ST-segment elevation myocardial infarction (NSTEMI).

Methods And Results: A total of 1042 patients presenting between August 2014 and April 2017 to the emergency department with the suspected acute coronary syndrome were included. Non-ST-segment elevation myocardial infarction was diagnosed per criteria of the fourth Universal definition of myocardial infarction (UDMI) using high-sensitivity troponin T (hs-cTnT). Expression levels of eleven microRNAs (miR-21, miR-22, miR-29a, miR-92a, miR-122, miR-126, miR-132, miR-133, miR-134, miR-191, and miR-423) were determined using RT-qPCR. Discrimination of NSTEMI was assessed for individual and a panel of miRNAs compared to the hs-cTnT reference using C-statistics and reclassification analysis. NSTEMI was diagnosed in 137 (13.1%) patients. The area under the curve (AUC) of the hs-cTnT based reference was 0.937. In a multivariate model, three miRNAs (miR-122, miR-133, and miR-134) were found to be associated with NSTEMI with AUCs between 0.506 and 0.656. A panel consisting of these miRNAs revealed an AUC of 0.662 for the diagnosis of NSTEMI. The AUC of the combination of the miRNA panel and troponin reference was significantly lower than the reference standard (AUC: 0.897 vs. 0.937, P = 0.006). Despite a significant improvement of NSTEMI reclassification measured by IDI and NRI, miRNAs did not improve the specificity of hs-cTnT kinetic changes for the diagnosis of NSTEMI (ΔAUC: 0.04).

Conclusion: Although single miRNAs are significantly associated with the diagnosis of NSTEMI a miRNA panel does not add diagnostic accuracy to the hs-cTnT reference considering baseline values and kinetic changes as recommended by the fourth version of UDMI.

Clinical Trials Identifier: NCT02116153.
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http://dx.doi.org/10.1093/ehjacc/zuaa034DOI Listing
January 2021

Age- and gender-related reference values of cardiac morphology and function in cardiovascular magnetic resonance.

Int J Cardiovasc Imaging 2021 Jan 22. Epub 2021 Jan 22.

Department of Cardiology, Angiology and Pneumology, University of Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

Cardiovascular magnetic resonance (CMR) is the reference standard for the quantitative assessment of cardiac morphology and function. The aim of the study was to determine age- and gender-related reference values for cardiac morphology and function according to current recommendations. 454 healthy volunteers (235 men, median age 52.0 (44.0-59.0) years) underwent a standard CMR scan and were divided into six groups of nearly equal size with regard to sex (male, female) and age (21-47 years, 48-57 years, 58-84 years). Left ventricular end-diastolic (LV-EDV) and end-systolic (LV-ESV) volumes and LV mass (LV-M) were measured at end-diastole and end-systole in steady-state free precession series with including papillary muscles and trabecular tissue in the LV-M. Absolute and indexed volumetric parameters were significantly different between gender groups with higher values in men compared to women (all p < 0.001). Furthermore, a significant age-dependent decline could be observed for left ventricular and right ventricular volumes (all p < 0.001), while LV-M did not show differences between the different age-groups. Parameters of longitudinal function for the left and right ventricle were higher in female compared to male subjects with a significant age-dependent decline. We provided normal values for cardiac volumes, function, and mass derived in accordance with current guidelines from a large population of healthy subjects, which can be implemented in clinical routine as a standard of reference.
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http://dx.doi.org/10.1007/s10554-021-02160-zDOI Listing
January 2021

NT-proBNP level before primary PCI and risk of poor myocardial reperfusion: Insight from the On-TIME II trial.

Am Heart J 2021 03 31;233:78-85. Epub 2020 Dec 31.

Department of Cardiology, Isala Heart Center, Zwolle, The Netherlands; Maastricht University Medical Center, Department of Cardiology, Maastricht, The Netherlands; Zuyderland Medical Center, Department of Cardiology, Heerlen, The Netherlands. Electronic address:

Background: N-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP), a marker for neurohumoral activation, has been associated with adverse outcome in patients with myocardial infarction. NT-proBNP levels may reflect extensive ischemia and microvascular damage, therefore we investigated the potential association between baseline NT-proBNP level and ST-resolution (STR), a marker of myocardial reperfusion, after primary percutaneous coronary intervention (pPCI).

Methods: we performed a post-hoc analysis of the On-TIME II trial (which randomized ST-elevation myocardial infarction (STEMI) patients to pre-hospital tirofiban administration vs placebo). Patients with measured NT-proBNP before angiography were included. Multivariate logistic-regression analyses was performed to investigate the association between baseline NTproBNP level and STR one hour after pPCI.

Results: Out of 984 STEMI patients, 918 (93.3%) had NT-proBNP values at baseline. Patients with STR <70% had higher NT-proBNP values compared to patients with complete STR (>70%) [Mean ±SD 375.2 ±1021.7 vs 1007.4 ±2842.3, Median (IQR) 111.7 (58.4-280.0) vs 168.0 (62.3-601.3), P <.001]. At multivariate logistic regression analysis, independent predictors associated with higher risk of poor myocardial reperfusion (STR <70%) were: NT-proBNP (OR 1.17, 95%CI 1.04-1.31, P = .009), diabetes mellitus (OR 1.87, 95%CI 1.14-3.07, P = .013), anterior infarct location (OR 2.74, 95% CI 2.00-3.77, P <.001), time to intervention (OR 1.06, 95%CI 1.01-1.11, P = .021), randomisation to placebo (OR 1.45, 95%CI 1.05-1.99, P = .022).

Conclusions: In STEMI patients, higher baseline NT-proBNP level was independently associate with higher risk of poor myocardial reperfusion, supporting the potential use of NT-proBNP as an early marker for risk stratification of myocardial reperfusion after pPCI in STEMI patients.
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http://dx.doi.org/10.1016/j.ahj.2020.12.017DOI Listing
March 2021

Analysis of Symptoms of COVID-19 Positive Patients and Potential Effects on Initial Assessment.

Open Access Emerg Med 2020 3;12:451-457. Epub 2020 Dec 3.

Casualty Department, University Hospital Heidelberg, Heidelberg, Germany.

Background: SARS-CoV-2 is a highly contagious virus, significantly impacting Germany among other countries since its emergence. Because of heterogeneous symptoms and a subset of patients even being asymptomatic at presentation, fast identification of infected patients remains challenging.

Objective: The goal of this study is the evaluation of different patient groups with a focus on symptoms and pre-existing illness at admission, as this is important for initial assessment and adequate emergency care.

Methods: COVID-19 positive patients at the University Hospital Heidelberg were retrospectively analyzed for disease history and symptoms at the initial presentation as well as mortality. The authors obtained institutional review board (IRB) approval by the Ethics Committee (Medical Faculty of Heidelberg University) prior to commencing the study.

Results: Dyspnea was more common in patients admitted to intermediate care/intensive care units (48 vs 13%, <0.001) and showed a significantly higher percentage in the deceased (91 vs 48%, =0.004). The symptoms of all presenting patients were highly variable, and many manifestations commonly associated with COVID-19 like cough, fever, and sore throat were only detected in a subset of patients, 60%, 43%, and 33%, respectively.

Conclusion: Dyspnea was present significantly more often in patients dying of COVID-19 compared to all patients admitted to the IMC/ICU, necessitating adequate observation and monitoring. In all presenting patients, initial symptoms showed large variation; therefore, COVID should be considered as a main differential diagnosis at every patient presentation, and patients with high pre-test probability should, if possible, be isolated until testing results are known.
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http://dx.doi.org/10.2147/OAEM.S275983DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721290PMC
December 2020

Peptide YY (PYY) Is Associated with Cardiovascular Risk in Patients with Acute Myocardial Infarction.

J Clin Med 2020 Dec 6;9(12). Epub 2020 Dec 6.

Department of Internal Medicine I-Cardiology, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.

Aims: Recent studies have found circulating concentrations of the gastrointestinal hormone GLP-1 to be an excellent predictor of cardiovascular risk in patients with myocardial infarction. This illustrates a yet not appreciated crosstalk between the gastrointestinal and cardiovascular systems, which requires further investigation. The gut-derived hormone Peptide YY (PYY) is secreted from the same intestinal L-cells as GLP-1. Relevance of PYY in the context of cardiovascular disease has not been explored. In this study, we aimed to investigate PYY serum concentrations in patients with acute myocardial infarction and to evaluate their association with cardiovascular events.

Material And Methods: PYY levels were assessed in 834 patients presenting with acute myocardial infarction (553 Non-ST-Elevation Myocardial Infarction (NSTEMI) and 281 ST-Elevation Myocardial Infarction (STEMI)) at the time of hospital admission. The composite outcomes of first occurrence of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke (3-P-MACE), and all-cause mortality were assessed with a median follow-up of 338 days.

Results: PYY levels were significantly associated with age and cardiovascular risk factors, including hypertension, diabetes, and kidney function in addition to biomarkers of heart failure (NT-pro BNP) and inflammation (hs-CRP). Further, PYY was significantly associated with 3-P-MACE (HR: 1.7; 95% CI: 1-2.97; = 0.0495) and all-cause mortality (HR: 2.69; 95% CI: 1.61-4.47; = 0.0001) by univariable Cox regression analyses, which was however lost after adjusting for multiple confounders.

Conclusions: PYY levels are associated with parameters of cardiovascular risk as well as cardiovascular events and mortality in patients presenting with acute myocardial infarction. However, this significant association is lost after adjustment for further confounders.
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http://dx.doi.org/10.3390/jcm9123952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762108PMC
December 2020

Prognostic Value of Elevated Copeptin and High-Sensitivity Cardiac Troponin T in Patients with and without Acute Coronary Syndrome: The ConTrACS Study.

J Clin Med 2020 Nov 11;9(11). Epub 2020 Nov 11.

Department of Internal Medicine III, Heidelberg University Hospital, 69120 Heidelberg, Germany.

Aims: We aimed to assess the prognostic role of copeptin in patients presenting to the emergency department with acute symptoms and increased high-sensitivity cardiac troponin T.

Methods: A total of 3890 patients presenting with acute symptoms to the emergency department of Heidelberg University Hospital were assessed for increased hs-cTnT (>14 ng/L) from three cohorts: the Heidelberg Acute Coronary Syndrome (ACS) Registry ( = 2477), the BIOPS Registry ( = 320), and the ACS OMICS Registry ( = 1093). In a pooled analysis, 1956 patients remained, comprising of 1600 patients with ACS and 356 patients with non-ACS.

Results: Median follow-up was 1468 days in the ACS cohort and 709 days in the non-ACS cohort. Elevated copeptin levels (>10 pmol/L) were found in 1174 patients (60.0%) in the entire cohort (58.1% in ACS and 68.5% in non-ACS, respectively) and mortality rates were significantly higher than in patients with normal copeptin levels (29.0% vs. 10.7%, < 0.001). In a multivariate Cox regression, elevated copeptin was independently associated with all-cause death in the ACS (HR = 1.7, 1.3-2.3, = 0.002) and non-ACS cohort (HR = 2.7, 1.4-5.0, = 0.0018).

Conclusion: Copeptin may aid in identifying patients at risk for adverse outcomes in patients with increased levels of hs-cTnT in ACS patients and in non-ACS conditions.
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http://dx.doi.org/10.3390/jcm9113627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696893PMC
November 2020

A Practical Approach for the Use of High-Sensitivity Cardiac Troponin Assays in the Evaluation of Patients With Chest Pain.

Am J Cardiol 2021 01 24;139:1-7. Epub 2020 Oct 24.

Medizinische Klinik III, Department of Cardiology, Angiology and Pneumology, University Hospital of Heidelberg, Heidelberg, Germany.

Chest pain is a common clinical presentation, especially in the emergency department. Both rapid identification of patients with myocardial infarction as well as those with noncardiac chest pain is important in order to start therapy in the former and avoid unnecessary investigations and delay in discharge in the latter. Beside electrocardiogram, cardiac biomarkers are a key element in decision making. Conventional creatinine kinase and troponin assays are not sensitive enough and have to be repeated at least 6 to 12 hours after initial evaluation. New high-sensitivity cardiac troponin (hs-cTn) tests are currently available and if used appropriately can substantially improve management. Because of their high sensitivity and accuracy, these tests allow measurement of very low serum troponin levels, such as those present in healthy individuals and can detect small changes in troponin concentration within a short time frame. These tests are thus, very useful for the early diagnosis of myocardial infarction but can also be elevated in several other conditions that result in myocardial injury. A good understanding of the analytical characteristics of these assays is of uppermost importance for their appropriate use in clinical practice.
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http://dx.doi.org/10.1016/j.amjcard.2020.10.037DOI Listing
January 2021

Appropriateness of CT pulmonary angiograms according to current diagnostic guidelines based on risk stratification: A retrospective single-center study.

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2021 Mar 22;165(1):51-56. Epub 2020 Oct 22.

Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Germany.

Background And Aim: Assessment of appropriateness of CT pulmonary angiograms (CTPA) in patients with suspected pulmonary embolism (PE) is based on risk stratification algorithms such as simplified the Geneva Score (sGS) in combination with D-dimer blood tests. The aim of this study was to validate the diagnostic yield and appropriateness of CTPA examinations in accordance with 2014 European Society of Cardiology (ESC) guidelines.

Materials And Methods: Data from 155 outpatients who underwent CTPA for clinical suspicion of PE were gathered from the radiology information system (RIS) and the clinical information system (CIS). We assessed the presence of sGS items and D-dimer blood test results in RIS from CTPA request forms and from clinical documentation in CIS.

Results: Based on the RIS, there were 2.6% patients with high (sGS≥3) and 97.4% patients with low pre-test PE probability (sGS<3), and CTPA indication was formally comprehendible in 75.5% using sGS and D-dimer blood tests. Based on RIS and CIS data in combination, there were 41.3% patients with high and 58.7% patients with low pre-test PE probability, and CTPA indication was formally comprehendible in 88.4%. Using RIS and CIS in combination, PE probability was upgraded from low to high probability in 39.7% compared with RIS alone. In 12.9%, there was a lack of data in RIS for CTPA justification.

Conclusion: There is a high diagnostic yield when applying current diagnostic guidelines to our data. There was however a notable discrepancy between the data transferred to the CTPA request forms from the full clinical documentation, therefore not readily available for clinical decision making.
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http://dx.doi.org/10.5507/bp.2020.049DOI Listing
March 2021

Copeptin combined with either non-high sensitivity or high sensitivity cardiac troponin for instant rule-out of suspected non-ST segment elevation myocardial infarction.

Biomarkers 2020 Dec 31;25(8):649-658. Epub 2020 Oct 31.

3rd Department of Internal Medicine, Cardiology and Intensive Care Medicine, Wilhelminenhospital, Vienna, Austria.

Background: Whether Copeptin combined with high sensitivity troponin below the respective decision cut-offs improves rule-out of NSTEMI and may predict all-cause death at 30-day is under debate.

Methods: Data on 10,329 patients from 5 trials were pooled to evaluate the diagnostic and prognostic performance of an initial Copeptin below decision cut-off in combination with a (hs)-cTn below the uppler limit of normal (ULN) compared to a) the initial (hs)-cTn alone in the standard serial sampling strategy based on the 99th percentile and b) a single marker strategy (SMS) based on hs-cTn < limit of detection. Endpoints were sensitivities and negative predictive values (NPV) for rule-out of NSTEMI, 30-day all-cause mortality and rates of eligibility for DMS or SMS.

Results: NPV for NSTEMI was higher for DMS than for the initial cTn, regardless assay sensitivity. The highest NPVs were observed with DMS vs. hs-cTn (99.4% [95% CI: 99.0%-99.6%] vs. 98.8% [98.4%-99.1%],) , and improved performance was consistent across all important subgroups including presentation <3 h, again irrespective of assay sensitivity. The point estimate of all NPVs for all-cause death exceeded 99.75%. In the label populations, DMS versus SMS demonstrated comparably high NPVs for rule-out of NSTEMI (99.4% [99.0%-99.6%] vs. 99.9% [99.2%-100.0%]), very low mortality after rule-out (0.1% [0.0%-0.4% vs. 0.0% [0.0%-1.2%]), but eligibility for rule-out was 2.4-fold higher (61.4% [59.9%-62.9%] vs. 25.3% [23.7%-26.9%]) with DMS than SMS.

Conclusion: Findings from a large pooled cohort corroborate the safety of the dual marker strategy for instant rule-out of NSTEMI, extending evidence to hs-cTn. Copeptin below cut-off in combination with hs-cTn below ULN may be used in more than 2.4-times more patients presenting with suspected ACS than a single marker strategy based on very low hs-cTn, without the need to exclude very early presenters or other important subgroups.
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http://dx.doi.org/10.1080/1354750X.2020.1833084DOI Listing
December 2020

Effects of crowding in the emergency department on the diagnosis and management of suspected acute coronary syndrome using rapid algorithms: an observational study.

BMJ Open 2020 10 8;10(10):e041757. Epub 2020 Oct 8.

Department of Cardiology, Angiology and Pulmonology, Heidelberg University Hospital, Heidelberg, Germany

Objectives: Fast diagnostic algorithms using high-sensitivity troponin (hsTn) in suspected acute coronary syndrome (ACS) are regarded as beneficial to expedite diagnosis and safe discharge of patients in crowded emergency departments (ED). This study investigates the effects of crowding on process times related to the diagnostic protocol itself or other time delays, and outcomes.

Design: Prospective single-centre observational study.

Setting: ED (Germany).

Participants: Final study population of 2525 consecutive patients with suspected ACS within 12 months, after exclusion of patients with ST-elevation myocardial infarction, missing blood samples, referral from other hospitals or repeated visits.

Interventions: Use of fast algorithms as per 2015 European Society of Cardiology guidelines.

Main Outcome Measures: Crowding was defined as mismatch between patient numbers and monitoring capacities, or mean physician time per case, categorised as normal, high and very high crowding. Outcome measures were length of ED stay, direct discharge from ED, laboratory turn around times (TAT), utilisation of fast algorithms, absolute and relative non-laboratory time, as well as mortality.

Results: Crowding was associated with increased length of ED stay (3.75-4.89 hours, p<0.001). While median TAT of the first hsTnT increased (53-57 min, p<0.001), total TAT of serial hsTnT did not increase significantly with higher crowding (p=0.170). Lower utilisation of fast algorithms (p=0.009) and increase of additional hsTnT measurements after diagnosis (p=0.001) were observed in higher crowding. Most importantly, crowding was significantly associated with prolonged absolute (p<0.001), and particularly relative non-laboratory time (63.3%-71.3%, p<0.001). However, there was no significant effect of crowding on mortality, even after adjustment for relevant clinical variables.

Conclusions: Process times, and particularly non-laboratory times, are prolonged in a crowded ED diminishing some positive effects of fast diagnostic algorithms in suspected ACS. Higher crowding levels were not significantly associated with higher all-cause mortality rates.

Trial Registration Number: NCT03111862.
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http://dx.doi.org/10.1136/bmjopen-2020-041757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545662PMC
October 2020

[Comparison between chest pain units and stroke units : Essential components of the vascular emergency care system: comparison of structure, certification process, quality benchmarking and reimbursement].

Herz 2020 Sep 29. Epub 2020 Sep 29.

Zentrum für Kardiologie, Kardiologie I, Universitätsmedizin Mainz, Mainz, Deutschland.

Background: Chest pain units (CPU) and stroke units (SU) have both become established as essential components of clinical emergency care. For both instances dedicated certification processes are installed. Up to summer 2020, 290 CPUs and 335 SUs have been successfully certified.

Objective: The aim of this review is to compare the structures and the current certification situation of CPUs and SUs. Also, the younger CPU certification process is compared to the long established SU certification standard.

Material Und Methods: The comparison includes the historical background, the certification process, quality benchmarking, possible additive structures, the current status of certification in Germany, the transfer of the concept to the European level as well as reimbursement issues.

Results: Both certification concepts show clear analogies. Evidence for SUs is supported by a positive Cochrane analysis and for CPUs there are many studies from the German CPU registry. The main differences include a uniform CPU system versus a multistep SU system of certification. Furthermore, SU have obligatory elements of quality documentation but only facultative quality indicator assessment for CPUs. From an economic viewpoint operation and procedural key (OPS) numbers guarantee a better reflection of the use of resources in the complex treatment of stroke, which could not yet be established for CPUs.

Conclusion: The well-established CPU concept could additionally benefit from a superordinate quality control. Adequate quality benchmarking appears to be fundamental for gap analyses and for the establishment of a separate remuneration structure. In this respect the German Society for Cardiology as the certifying institution is required to establish an appropriate mechanism within the framework of regular updates of criteria.
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http://dx.doi.org/10.1007/s00059-020-04984-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7523490PMC
September 2020

Gender Differences in Patients Admitted to a Certified German Chest Pain Unit: Results from the German Chest Pain Unit Registry.

Cardiology 2020 11;145(9):562-569. Epub 2020 Aug 11.

3rd Department of Medicine, University Hospital Heidelberg, Heidelberg, Germany.

Introduction: Gender-specific atypical clinical presentation in acute coronary syndrome and sex-specific outcomes in cardiovascular disease in women are well known. The aim of this study is to analyze possible differences between men and women presenting to certified German chest pain units (CPUs).

Methods: Data from 13,900 patients derived from the German CPU registry were analyzed for gender differences in patient characteristics, cardiovascular disease manifestation, critical time intervals, treatment and prognosis.

Results: A total of 37.8% of patients were female. Typical chest pain occurred more frequently in men, while atypical symptoms occurred more frequently in women. Female gender was associated with longer pre- and in-hospital time delays. Women were more often diagnosed with a nonischemic origin of pain. In a 3-month follow-up, there was no gender-specific difference in combined major adverse coronary and cerebrovascular events.

Discussion/conclusion: This study points out gender-specific differences in prehospital time intervals and a significantly higher percentage of atypical symptoms in suspected myocardial ischemia as well as more noncoronary diagnoses in women. Symptom awareness and a broader diagnostic workup in women are essential.
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http://dx.doi.org/10.1159/000509276DOI Listing
August 2020

Instant rule-out of suspected non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin T with Copeptin versus a single low high-sensitivity cardiac troponin T: findings from a large pooled individual data analysis on 10,329 patients.

Clin Res Cardiol 2021 Feb 15;110(2):194-199. Epub 2020 Jul 15.

Department of Emergency Medicine, Campus Mitte and Virchow, Berlin, Germany.

Background: Evidence is sparse and inconsistent on the role of a dual marker strategy (DMS) combining Copeptin with cardiac troponin T (cTnT) for instant rule-out of a non-ST-segment myocardial infarction (NSTEMI) when high sensitivity cardiac troponin T (hs-cTnT) is used.

Methods: Data on 10,329 patients from 5 trials were pooled to evaluate initial Copeptin in combination with hs-cTnT against a single marker strategy (SMS) based on hs-cTnT < limit of detection. Endpoints were sensitivities and negative predictive values (NPV) for rule-out of NSTEMI, 30-day all-cause mortality and rates of applicability for DMS or SMS.

Results: NPV for rule-out of NSTEMI was high, exceeding 99.0% for the lower limits of the 95% confidence intervals (99.0% vs 99.2%) for DMS and SMS, and NPV for all cause death at 30 days was similar with very low mortality after rule-out [0.07% (0.0-0.4%) vs 0.0% (0.0-1.2%), p = 1.0], but applicability was 2.4-fold higher [64.6% (63.0-66.2%) vs 27.9% (26.2%-29.7%), p < 0.001] with DMS than SMS. In a secondary analysis on DMS after inclusion of high risk patients, performance and applicability were similar.

Conclusion: Findings corroborate the 2015 European Society of Cardiology recommendation to use dual marker strategy for instant rule-out of NSTEMI, extending evidence to hs-cTnT. Novel data demonstrate a comparably safe and effective instant rule-out with Copeptin in combination with hs-cTnT versus a single marker strategy based on very low hs-cTnT but a more than twofold higher applicability of the dual marker strategy without the need to exclude very early presenters or other important subgroups. Dual marker strategy using hs-cTnT at 99th percentile and Copeptin versus ESC 0-h immediate rule-out based on hs-cTnT < limit of detection.
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http://dx.doi.org/10.1007/s00392-020-01712-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862196PMC
February 2021

[Cardiac biomarkers and COVID-19 - Phenotypes and Interpretation].

Dtsch Med Wochenschr 2020 Jun 3;145(11):755-760. Epub 2020 Jun 3.

Universitätsklinikum Heidelberg, Abteilung Innere Medizin III, Kardiologie, Angiologie und Pneumologie.

Current pandemic caused by SARS-CoV-2 inducing viral COVID-19 pneumonia, is categorized in 3 stages. Some biomarkers could be assigned to one of these stages, showing a correlation to mortality in COVID-19 patients. Laboratory findings in COVID-19, especially when serially evaluated, may represent individual disease severity and prognosis. These may help planning and controlling therapeutic interventions. Biomarkers for myocardial injury (high sensitive cardiac troponin, hsTn) or hemodynamic stress (NTproBNP) may occur in COVID-19 pneumonia such as in other pneumonias, correlating with severity and prognosis of the underlying disease. In hospitalized COVID-19 patients' mild increases of hsTn or NTproBNP may be explained by cardiovascular comorbidities and direct or indirect cardiac damage or stress caused by or during COVID-19 pneumonia. In case of suspected NSTE-ACS and COVID-19, indications for echocardiography or reperfusion strategy should be carefully considered against the risk of contamination.
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http://dx.doi.org/10.1055/a-1158-5756DOI Listing
June 2020

Capacity changes in German certified chest pain units during COVID-19 outbreak response.

Clin Res Cardiol 2020 Dec 31;109(12):1469-1475. Epub 2020 May 31.

Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center Essen, University Duisburg-Essen, Essen, Germany.

Background: We sought to determine structure and changes in organisation and bed capacities of certified German chest pain units (CPU) in response to the emergency plan set-up as a response to the SARS-CoV-2 pandemic.

Methods And Results: The study was conducted in the form of a standardised telephone interview survey in certified German CPUs. Analyses comprised the overall setting of the CPU, bed capacities, possibilities for ventilation, possible changes in organisation and resources, chest pain patient admittance, overall availability of CPUs and bail-out strategies. The response rate was 91%. Nationwide, CPU bed capacities decreased by 3% in the early phase of COVID-19 pandemic response, exhibiting differences within and between the federal states. Pre-pandemic and pandemic bed capacities stayed below 1 CPU bed per 50,000 inhabitants. 97% of CPUs were affected by internal reorganisation pandemic plans at variable extent. While we observed a decrease of CPU beds within an emergency room (ER) set-up and on intermediate care units (ICU), beds in units being separated from ER and ICU were even increased in numbers.

Conclusions: Certified German CPUs are able to maintain adequate coverage for chest pain patients in COVID-19 pandemic despite structural changes. However, at this time, it appears important to add operating procedures during pandemic outbreaks to the certification criteria of forthcoming guidelines either at the individual CPU level or more centrally steered by the German Cardiac Society or the European Society of Cardiology.
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http://dx.doi.org/10.1007/s00392-020-01676-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261510PMC
December 2020

Biomarkers for infarct diagnosis and rapid rule-out/rule-in of acute myocardial infarction.

Herz 2020 Sep;45(6):509-519

Medizinische Klinik III, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany.

The 4th edition of the Universal Definition of Myocardial Infarction (MI) recommends measurement of cardiac troponin (cTn) T or I for the diagnosis of MI due to their absolute cardiac tissue specificity. In this MI definition, values exceeding the 99th percentile of a healthy reference population distinguish between detectable troponin due to physiological cell turnover as opposed to pathological myocardial injury. In clinical routine, high-sensitivity (hs) troponin assays that allow earlier diagnosis of MI and detection of myocardial injury that would have escaped detection due to the lower sensitivity of previous assay generations are increasingly used. While the 2015 European Society of Cardiology (ESC) guidelines already recommend a re-testing of cTn after 3 h, if an hs-cTn assay is available, faster protocols that reassess hs-cTn after 60-120 min are increasingly performed, since these protocols allow faster patient disposition, increase discharge rates from the emergency department (ED), and are at least as safe as the standard protocol for the guidance of discharge after rule-out. However, decision cut-offs are lower than the 99th percentile and concentration change criteria depend on the individual hs-cTn assay and protocol used. The following article provides an overview of the recommendations of the 4th universal MI definition as well as the current 2015 ESC guidelines on cTn and other potential biomarker candidates for patients presenting with suspected acute coronary syndromes. Limitations and areas of controversy are discussed.
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http://dx.doi.org/10.1007/s00059-020-04943-xDOI Listing
September 2020

Coronavirus Disease 2019 (COVID-19) and its implications for cardiovascular care: expert document from the German Cardiac Society and the World Heart Federation.

Clin Res Cardiol 2020 Dec 27;109(12):1446-1459. Epub 2020 May 27.

Department of Medicine-Cardiology,, J.W. Goethe University, Frankfurt, Germany.

Coronavirus diseases 2019 (COVID-19) has become a worldwide pandemic affecting people at high risk and particularly at advanced age, cardiovascular and pulmonary disease. As cardiovascular patients are at high risk but also have dyspnea and fatigue as leading symptoms, prevention, diagnostics and treatment in these patients are important to provide adequate care for those with or without COVID-19 but most importantly when comorbid cardiovascular conditions are present. Severe COVID-19 with acute respiratory distress (ARDS) is challenging as patients with elevated myocardial markers such as troponin are at enhanced high risk for fatal outcomes. As angiotensin-converting enzyme 2 (ACE2) is regarded as the viral receptor for cell entry and as the Coronavirus is downregulating this enzyme, which provides cardiovascular and pulmonary protection, there is ongoing discussions on whether treatment with cardiovascular drugs, which upregulate the viral receptor ACE2 should be modified. As most of the COVID-19 patients have cardiovascular comorbidities like hypertension, diabetes, coronary artery disease and heart failure, which imposes a high risk on these patients, cardiovascular therapy should not be modified or even withdrawn. As cardiac injury is a common feature of COVID-19 associated ARDS and is linked with poor outcomes, swift diagnostic management and specialist care of cardiovascular patients in the area of COVID-19 is of particular importance and deserves special attention.
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http://dx.doi.org/10.1007/s00392-020-01656-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252421PMC
December 2020

Application of the fourth universal definition of myocardial infarction in clinical practice.

Biomarkers 2020 Jun 14;25(4):322-330. Epub 2020 May 14.

Department of Medical Sciences, Uppsala University and Uppsala Clinical Research Center, Uppsala University, Sweden.

The Fourth Universal Definition of Myocardial Infarction (MI) has highlighted the different pathophysiological mechanisms that may lead to ischaemic and non-ischaemic myocardial injury and has emphasised that the diagnosis of myocardial infarction requires the presence of acute myocardial ischaemia in the setting of acute myocardial injury. This case based review intends to illustrate basic principles on how to apply this new, revised definition in clinical practice. The distinction between different types of MIs (type 1 or type 2) and the delineation of MI from acute non-ischaemic myocardial injury may be challenging in individual patients, which is illustrated by presenting and discussing real-life routine cases. Type 1 MI is a consequence of coronary plaque rupture or erosion with intracoronary thrombus formation that is usually apparent on coronary angiography. Plausible triggering mechanisms causing myocardial oxygen supply/demand mismatch must be identified for the diagnosis of type 2 MI and its treatment should focus initially on management of the underlying disease attributable to acute myocardial ischaemia.
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http://dx.doi.org/10.1080/1354750X.2020.1764108DOI Listing
June 2020

microRNA neural networks improve diagnosis of acute coronary syndrome (ACS).

J Mol Cell Cardiol 2021 02 17;151:155-162. Epub 2020 Apr 17.

Department of Internal Medicine III, Heidelberg University, Heidelberg, Germany; DZHK (German Centre for Cardiovascular Research), Germany; Department of Genetics, Stanford Genome Technology Center, Stanford University School of Medicine, Stanford, CA, USA. Electronic address:

Background: Cardiac troponins are the preferred biomarkers of acute myocardial infarction. Despite superior sensitivity, serial testing of Troponins to identify patients suffering acute coronary syndromes is still required in many cases to overcome limited specificity. Moreover, unstable angina pectoris relies on reported symptoms in the troponin-negative group. In this study, we investigated genome-wide miRNA levels in a prospective cohort of patients with clinically suspected ACS and determined their diagnostic value by applying an in silico neural network.

Methods: PAXgene blood and serum samples were drawn and hsTnT was measured in patients at initial presentation to our Chest-Pain Unit. After clinical and diagnostic workup, patients were adjudicated by senior cardiologists in duty to their final diagnosis: STEMI, NSTEMI, unstable angina pectoris and non-ACS patients. ACS patients and a cohort of healthy controls underwent deep transcriptome sequencing. Machine learning was implemented to construct diagnostic miRNA classifiers.

Results: We developed a neural network model which incorporates 34 validated ACS miRNAs, showing excellent classification results. By further developing additional machine learning models and selecting the best miRNAs, we achieved an accuracy of 0.96 (95% CI 0.96-0.97), sensitivity of 0.95, specificity of 0.96 and AUC of 0.99. The one-point hsTnT value reached an accuracy of 0.89, sensitivity of 0.82, specificity of 0.96, and AUC of 0.96.

Conclusions: Here we show the concept of neural network based biomarkers for ACS. This approach also opens the possibility to include multi-modal data points to further increase precision and perform classification of other ACS differential diagnoses.
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http://dx.doi.org/10.1016/j.yjmcc.2020.04.014DOI Listing
February 2021

Safety and efficacy of the European Society of Cardiology 0/1-hour algorithm for diagnosis of myocardial infarction: systematic review and meta-analysis.

Heart 2020 Jul 3;106(13):985-991. Epub 2020 Apr 3.

Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan

Objective: The European Society of Cardiology (ESC) 0/1 hour algorithm has been primarily validated in Europe, America and Australasia with less knowledge of its performance outside of these settings. We aim to evaluate the performance of the ESC 0/1 hour algorithm across different contexts.

Methods: We searched PubMed, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials for relevant studies published between 1 January 2008 and 31 May 2019. The primary outcome was index myocardial infarction and the secondary outcome was major adverse cardiac event or mortality. A bivariate random-effects meta-analysis was used to derive the pooled estimate of each outcome.

Results: A total of 11 014 patients from 10 cohorts were analysed for the primary outcome. The algorithm based on high-sensitivity cardiac troponin (hs-cTn)T (Roche), hs-cTnI (Abbott) and hs-cTnI (Siemens) had pooled sensitivity of 98.4% (95% CI=95.1% to 99.5%), 98.1% (95% CI=94.6% to 99.3%) and 98.7% (95% CI=97.3% to 99.3%), respectively. The algorithm based on hs-cTnT (Roche) and hs-cTnI (Siemens) had pooled specificity of 91.2% (95% CI=86.0% to 94.6%) and 95.9% (95% CI=94.1% to 97.2%), respectively. Among patients in the rule-out category, the pooled mortality rate at 30 days and at 1 year was 0.1% (95% CI=0.0% to 0.4%) and 0.8% (95% CI=0.5% to 1.2%), respectively. Among patients in the observation zone, the pooled mortality rate was 0.7% (95% CI=0.3% to 1.2%) at 30 days but increased to 8.1% (95% CI=6.1% to 10.4%) at 1 year, comparable to the mortality rate in the rule-in group.

Conclusion: The ESC 0/1 hour algorithm has high diagnostic accuracy but may not be sufficiently safe if the 1% miss-rate for myocardial infarction is desired.

Prospero Registration Number: CRD42019142280.
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http://dx.doi.org/10.1136/heartjnl-2019-316343DOI Listing
July 2020

German chest pain unit registry: data review after the first decade of certification.

Herz 2021 Apr 30;46(Suppl 1):24-32. Epub 2020 Mar 30.

Institute for Myocardial Infarction Research Foundation, Ludwigshafen, Germany.

In 2008, the German Cardiac Society (GCS) introduced a certification program for specialized chest pain units (CPUs). In order to benchmark the performance of the certified CPUs, a nationwide German CPU registry was established. Since then, data for more than 34,000 patients have been included. The concept of certified CPUs in Germany has been widely accepted and its success is underlined by its recent inclusion in national and international guidelines. As of December 2019, 286 CPUs have been successfully certified or recertified by the GCS. This review focuses on the data retrieved from the CPU registry during the first decade of certification. As demonstrated by 16 manuscripts stemming from the registry, certified German CPUs demonstrate high quality of care in acute coronary syndrome and beyond. It is also noted that the German CPU registry allowed for further analysis of the gap in guideline adherence. With the current update of the CPU certification criteria, central data collection as a best-practice criterion will be abandoned, and after some productive years the registry has temporarily been stopped.
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http://dx.doi.org/10.1007/s00059-020-04912-4DOI Listing
April 2021

Diagnostic performance of D-dimer in predicting venous thromboembolism and acute aortic dissection.

Eur Heart J Acute Cardiovasc Care 2020 Mar 18:2048872620907322. Epub 2020 Mar 18.

Department of Internal Medicine III, Cardiology, Angiology and Pulmonology, Heidelberg University Hospital, Germany.

Background: D-dimer is elevated in a variety of conditions. The purpose of this study was to assess the positive predictive value of D-dimer to rule in patients with confirmed pulmonary embolism, deep vein thrombosis, acute aortic dissection or thrombosis of the upper extremity in comparison to patients with elevated D-dimer for other reasons.

Methods And Results: We studied 1334 patients presenting to the emergency department with pulmonary embolism (=193), deep vein thrombosis (=73), acute aortic dissection (=22), thrombosis of the upper extremity (=8) and 1038 controls. The positive predictive value was increased with higher D-dimer concentrations improving the ability to identify diseases with high thrombus burden. Patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity showed a maximum positive predictive value of 85.2% at a D-dimer level of 7.8 mg/L (95% confidence interval (CI) 78.1 to 90.4). The maximum positive predictive value was lower in cancer patients with venous thromboembolism, acute aortic dissection and thrombosis of the upper extremity, reaching 68.9% at a D-dimer level of 7.5 mg/L (95% CI 57.4 to 78.4). The positive likelihood ratio was very consistent with the positive predictive value. Using a cut-off level of 0.5 mg/L, D-dimer showed a high sensitivity of at least 93%, but a very low specificity of nearly 0%. Conversely, an optimised cut-off value of 4.6 mg/L increased specificity to 95% for the detection of life-threatening venous thromboembolism, acute aortic dissection or thrombosis of the upper extremity at the costs of moderate sensitivities (58% for pulmonary embolism, 41% for deep vein thrombosis, 65% for pulmonary embolism with co-existent deep vein thrombosis, 50% for acute aortic dissection and 13% for thrombosis of the upper extremity). Using the same cut-off in cancer patients, higher values were observed for sensitivity at a specificity level of more than 95%. The area under the curve for the discrimination of venous thromboembolism/acute aortic dissection/thrombosis of the upper extremity from controls was significantly higher in cancer versus non-cancer patients (area under the curve 0.905 in cancer patients, 95% CI 0.89 to 0.92, vs. area under the curve 0.857 in non-cancer patients, 95% CI 0.84 to 0.88; =0.0349).

Conclusion: D-dimers are useful not only to rule out but also to rule in venous thromboembolism and acute aortic dissection with an at least moderate discriminatory ability, both in patients with and without cancer.
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http://dx.doi.org/10.1177/2048872620907322DOI Listing
March 2020