|
1
|
Albus M, Zimmermann T, Median D, Rumora K, Isayeva G, Amrein M, Schaefer I, Walter J, Michel E, Huré G, Strebel I, Caobelli F, Haaf P, Frey SM, Mueller C, Zellweger MJ. Combining anatomical and biochemical markers in the detection and risk stratification of coronary artery disease. Eur Heart J Cardiovasc Imaging 2024; 25:1197-1205. [PMID: 38591997 PMCID: PMC11346366 DOI: 10.1093/ehjci/jeae093] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 03/08/2024] [Accepted: 03/25/2024] [Indexed: 04/10/2024] Open
Abstract
AIMS We aimed to test the hypothesis if combining coronary artery calcium score (Ca-score) as a quantitative anatomical marker of coronary atherosclerosis with high-sensitivity cardiac troponin as a quantitative biochemical marker of myocardial injury provided incremental value in the detection of functionally relevant coronary artery disease (fCAD) and risk stratification. METHODS AND RESULTS Consecutive patients undergoing myocardial perfusion single-photon emission computed tomography (MPS) without prior CAD were enrolled. The diagnosis of fCAD was based on the presence of ischaemia on MPS and coronary angiography; fCAD was centrally adjudicated in the diagnostic and prognostic domain. Diagnostic accuracy was evaluated using the area under the receiver-operating characteristic curve (AUC). The composite of cardiovascular death and non-fatal acute myocardial infarction (AMI) within 730 days was the primary prognostic endpoint. Among 1715 patients eligible for the diagnostic analysis, 399 patients had fCAD. The combination of Ca-score and high-sensitivity cardiac troponin T (hs-cTnT) had good diagnostic accuracy for the diagnosis of fCAD (AUC 0.79, 95% confidence interval (CI) 0.77-0.81), but no incremental value compared with the Ca-score alone (AUC 0.79, 95% CI 0.77-0.81, P = 0.965). Similar results were observed using high-sensitivity cardiac troponin I (AUC 0.80, 95% CI 0.77-0.82) instead of hs-cTnT. Among 1709 patients (99.7%) with available follow-up, 59 patients (3.5%) suffered the composite primary prognostic endpoint (non-fatal AMI, n = 34; CV death, n = 28). Both Ca-score and hs-cTnT had independent prognostic value. Increased risk was restricted to patients with elevation in both markers. CONCLUSION The combination of the Ca-score with hs-cTnT increases the prognostic accuracy for future events but does not provide incremental value vs. the Ca-score alone for the diagnosis of fCAD. STUDY REGISTRATION Clinical trial registration: NCT00470587.
Collapse
Affiliation(s)
- Miriam Albus
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
- Department of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Tobias Zimmermann
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
- Departement of Anesthesiology and Intensive Care, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Daniela Median
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| | - Klara Rumora
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| | - Ganna Isayeva
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| | - Melissa Amrein
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| | - Ibrahim Schaefer
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
- Department of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Joan Walter
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
- Department of Medical Oncology and Hematology, University Hospital Zurich, University of Zurich, Zürich, Switzerland
| | - Evita Michel
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| | - Gabrielle Huré
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| | - Ivo Strebel
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| | - Federico Caobelli
- Department of Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Philip Haaf
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| | - Simon M Frey
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| | - Christian Mueller
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| | - Michael J Zellweger
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland
| |
Collapse
|
|
2
|
Bock C, Walter JE, Rieck B, Strebel I, Rumora K, Schaefer I, Zellweger MJ, Borgwardt K, Müller C. Enhancing the diagnosis of functionally relevant coronary artery disease with machine learning. Nat Commun 2024; 15:5034. [PMID: 38866791 PMCID: PMC11169272 DOI: 10.1038/s41467-024-49390-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 05/31/2024] [Indexed: 06/14/2024] Open
Abstract
Functionally relevant coronary artery disease (fCAD) can result in premature death or nonfatal acute myocardial infarction. Its early detection is a fundamentally important task in medicine. Classical detection approaches suffer from limited diagnostic accuracy or expose patients to possibly harmful radiation. Here we show how machine learning (ML) can outperform cardiologists in predicting the presence of stress-induced fCAD in terms of area under the receiver operating characteristic (AUROC: 0.71 vs. 0.64, p = 4.0E-13). We present two ML approaches, the first using eight static clinical variables, whereas the second leverages electrocardiogram signals from exercise stress testing. At a target post-test probability for fCAD of <15%, ML facilitates a potential reduction of imaging procedures by 15-17% compared to the cardiologist's judgement. Predictive performance is validated on an internal temporal data split as well as externally. We also show that combining clinical judgement with conventional ML and deep learning using logistic regression results in a mean AUROC of 0.74.
Collapse
Affiliation(s)
- Christian Bock
- Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland
- Swiss Institute for Bioinformatics, Lausanne, Switzerland
| | - Joan Elias Walter
- Cardiovascular Research Institute Basel, University Hospital of Basel, University of Basel, Basel, Switzerland
- Department of Cardiology, University Hospital of Basel, University of Basel, Basel, Switzerland
- Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Bastian Rieck
- Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland
- Swiss Institute for Bioinformatics, Lausanne, Switzerland
- Institute of AI for Health, Helmholtz Munich and Technical University of Munich, Munich, Germany
| | - Ivo Strebel
- Cardiovascular Research Institute Basel, University Hospital of Basel, University of Basel, Basel, Switzerland
- Department of Cardiology, University Hospital of Basel, University of Basel, Basel, Switzerland
| | - Klara Rumora
- Cardiovascular Research Institute Basel, University Hospital of Basel, University of Basel, Basel, Switzerland
- Department of Cardiology, University Hospital of Basel, University of Basel, Basel, Switzerland
| | - Ibrahim Schaefer
- Cardiovascular Research Institute Basel, University Hospital of Basel, University of Basel, Basel, Switzerland
- Department of Cardiology, University Hospital of Basel, University of Basel, Basel, Switzerland
| | - Michael J Zellweger
- Cardiovascular Research Institute Basel, University Hospital of Basel, University of Basel, Basel, Switzerland
- Department of Cardiology, University Hospital of Basel, University of Basel, Basel, Switzerland
| | - Karsten Borgwardt
- Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
- Swiss Institute for Bioinformatics, Lausanne, Switzerland.
- Department of Machine Learning and Systems Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.
| | - Christian Müller
- Cardiovascular Research Institute Basel, University Hospital of Basel, University of Basel, Basel, Switzerland.
- Department of Cardiology, University Hospital of Basel, University of Basel, Basel, Switzerland.
| |
Collapse
|
|
3
|
Zabolotskikh I, Potievskaya V, Bautin A, Grigoryev E, Grigoryev S, Gritsan A, Kirov M, Kuzovlev A, Lebedinskii K, Subbotin V. Perioperative management of patients with coronary artery disease. Guidelines of the All-Russian Public Organization “Federation of Anaesthesiologists and Reanimatologists” (the 2nd revision). RUSSIAN JOURNAL OF ANESTHESIOLOGY AND REANIMATOLOGY 2024:6. [DOI: 10.17116/anaesthesiology20240516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
4
|
Isayeva G, Potlukova E, Rumora K, Lopez Ayala P, Kurun A, Leibfarth JP, Schäfer I, Michel E, Pesen K, Zellweger MJ, Trendelenburg M, Hejlesen TK, Hansen AG, Thiel S, Mueller C. Diagnostic and prognostic value of H-ficolin for functionally relevant coronary artery disease. Clin Chim Acta 2023; 551:117582. [PMID: 37802208 DOI: 10.1016/j.cca.2023.117582] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 10/03/2023] [Accepted: 10/03/2023] [Indexed: 10/08/2023]
Abstract
BACKGROUND We aimed to test the diagnostic and prognostic ability of H-ficolin, an initiator of the lectin pathway of the complement system, for functionally relevant coronary artery disease (fCAD), and explore its determinants. METHODS The presence of fCAD was adjudicated using myocardial perfusion imaging single-photon emission tomography and coronary angiography. H-ficolin levels were measured by a sandwich-type immunoassay at rest, peak stress-test, and 2 h after stress-test. Cardiovascular death and non-fatal myocardial infarction were assessed during 5-year follow-up. RESULTS Among 1,571 patients (32.3 % women), fCAD was detected in 462 patients (29.4 %). H-ficolin concentration at rest was 18.6 (15.3-21.8) µg/ml in patients with fCAD versus 17.8 (15.4-21.5) µg/ml, p = 0.33, in patients without fCAD, resulting in an AUC of 0.53 (95 %CI 0.48-0.56). During follow-up, 107 patients (6.8 %) had non-fatal myocardial infarction and 99 patients (6.3 %) experienced cardiovascular death. In Cox regression analysis, H-ficolin was not a predictor of events in the overall cohort. Subgroup analysis suggested a potential link between H-ficolin and non-fatal myocardial infarction in patients without fCAD (adjusted HR 1.03, 95 % CI 1.02-1.15, p = 0.005). H-ficolin concentration showed a weak positive correlation with systolic (r = 0.069, p < 0.001) and diastolic blood pressure (r = 0.111, p < 0.001). CONCLUSION H-ficolin concentration did not have diagnostic and/or prognostic value in patients referred for fCAD work-up.
Collapse
Affiliation(s)
- Ganna Isayeva
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, University of Basel, Switzerland.
| | - Eliska Potlukova
- Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland
| | - Klara Rumora
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, University of Basel, Switzerland
| | - Pedro Lopez Ayala
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, University of Basel, Switzerland
| | - Atakan Kurun
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, University of Basel, Switzerland
| | - Jan-Philipp Leibfarth
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, University of Basel, Switzerland
| | - Ibrahim Schäfer
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, University of Basel, Switzerland
| | - Evita Michel
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, University of Basel, Switzerland
| | - Kaan Pesen
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, University of Basel, Switzerland
| | - Michael J Zellweger
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, University of Basel, Switzerland
| | - Marten Trendelenburg
- Department of Internal Medicine, University Hospital Basel, University of Basel, Switzerland
| | | | | | - Steffen Thiel
- Department of Biomedicine, Aarhus University, Denmark
| | - Christian Mueller
- Cardiovascular Research Institute Basel (CRIB), University Heart Center, University Hospital Basel, University of Basel, Switzerland.
| |
Collapse
|
|
5
|
Buergin N, Lopez-Ayala P, Hirsiger JR, Mueller P, Median D, Glarner N, Rumora K, Herrmann T, Koechlin L, Haaf P, Rentsch K, Battegay M, Banderet F, Berger CT, Mueller C. Sex-specific differences in myocardial injury incidence after COVID-19 mRNA-1273 booster vaccination. Eur J Heart Fail 2023; 25:1871-1881. [PMID: 37470105 DOI: 10.1002/ejhf.2978] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Revised: 07/04/2023] [Accepted: 07/05/2023] [Indexed: 07/21/2023] Open
Abstract
AIMS To explore the incidence and potential mechanisms of oligosymptomatic myocardial injury following COVID-19 mRNA booster vaccination. METHODS AND RESULTS Hospital employees scheduled to undergo mRNA-1273 booster vaccination were assessed for mRNA-1273 vaccination-associated myocardial injury, defined as acute dynamic increase in high-sensitivity cardiac troponin T (hs-cTnT) concentration above the sex-specific upper limit of normal on day 3 (48-96 h) after vaccination without evidence of an alternative cause. To explore possible mechanisms, antibodies against interleukin-1 receptor antagonist (IL-1RA), the SARS-CoV-2-nucleoprotein (NP) and -spike (S1) proteins and an array of 14 inflammatory cytokines were quantified. Among 777 participants (median age 37 years, 69.5% women), 40 participants (5.1%; 95% confidence interval [CI] 3.7-7.0%) had elevated hs-cTnT concentration on day 3 and mRNA-1273 vaccine-associated myocardial injury was adjudicated in 22 participants (2.8% [95% CI 1.7-4.3%]). Twenty cases occurred in women (3.7% [95% CI 2.3-5.7%]), two in men (0.8% [95% CI 0.1-3.0%]). Hs-cTnT elevations were mild and only temporary. No patient had electrocardiographic changes, and none developed major adverse cardiac events within 30 days (0% [95% CI 0-0.4%]). In the overall booster cohort, hs-cTnT concentrations (day 3; median 5, interquartile range [IQR] 4-6 ng/L) were significantly higher compared to matched controls (n = 777, median 3 [IQR 3-5] ng/L, p < 0.001). Cases had comparable systemic reactogenicity, concentrations of anti-IL-1RA, anti-NP, anti-S1, and markers quantifying systemic inflammation, but lower concentrations of interferon (IFN)-λ1 (IL-29) and granulocyte-macrophage colony-stimulating factor (GM-CSF) versus persons without vaccine-associated myocardial injury. CONCLUSION mRNA-1273 vaccine-associated myocardial injury was more common than previously thought, being mild and transient, and more frequent in women versus men. The possible protective role of IFN-λ1 (IL-29) and GM-CSF warrant further studies.
Collapse
Affiliation(s)
- Natacha Buergin
- Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Pedro Lopez-Ayala
- Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Julia R Hirsiger
- Department of Biomedicine, Translational Immunology, University of Basel, Basel, Switzerland
| | - Philip Mueller
- Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Daniela Median
- Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Noemi Glarner
- Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Klara Rumora
- Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Timon Herrmann
- Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Luca Koechlin
- Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Philip Haaf
- Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Katharina Rentsch
- Department of Laboratory Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Manuel Battegay
- Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Florian Banderet
- Department of Internal Medicine, Medical Outpatient Unit, University Hospital Basel, Basel, Switzerland
- Health Service, University Hospital Basel, Basel, Switzerland
| | - Christoph T Berger
- Department of Biomedicine, Translational Immunology, University of Basel, Basel, Switzerland
- University Center for Immunology, University Hospital Basel, Basel, Switzerland
| | - Christian Mueller
- Department of Cardiology and Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| |
Collapse
|
|
6
|
Levi N, Hasin T. Myocardial injury related to SARS-CoV-2 mRNA vaccination: The plot thickens. Eur J Heart Fail 2023; 25:1882-1883. [PMID: 37642187 DOI: 10.1002/ejhf.3013] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 08/22/2023] [Indexed: 08/31/2023] Open
Affiliation(s)
- Nir Levi
- Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Tal Hasin
- Jesselson Integrated Heart Center, Shaare Zedek Medical Center, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| |
Collapse
|
|
7
|
Wereski R, Adamson P, Shek Daud NS, McDermott M, Taggart C, Bularga A, Kimenai DM, Lowry MTH, Tuck C, Anand A, Lowe DJ, Chapman AR, Mills NL. High-Sensitivity Cardiac Troponin for Risk Assessment in Patients With Chronic Coronary Artery Disease. J Am Coll Cardiol 2023; 82:473-485. [PMID: 37532417 DOI: 10.1016/j.jacc.2023.05.046] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 05/09/2023] [Accepted: 05/11/2023] [Indexed: 08/04/2023]
Abstract
BACKGROUND Cardiac troponin is used for risk stratification of patients with acute coronary syndromes; however, the role of testing in other settings remains unclear. OBJECTIVES The aim of this study was to evaluate whether cardiac troponin testing could enhance risk stratification in patients with chronic coronary artery disease independent of disease severity and conventional risk measures. METHODS In a prospective cohort of consecutive patients with symptoms suggestive of stable angina attending for outpatient coronary angiography, high-sensitivity cardiac troponin I was measured before angiography, and clinicians were blinded to the results. The primary outcome was myocardial infarction or cardiovascular death during follow-up. RESULTS In 4,240 patients (age 66 years [IQR: 59-73 years], 33% female), coronary artery disease was identified in 3,888 (92%) who had 255 (6%) primary outcome events during a median follow-up of 2.4 years (IQR: 1.3-3.6 years). In patients with coronary artery disease, troponin concentrations were 2-fold higher in those with an event compared with those without (6.7 ng/L [IQR: 3.2-14.2 ng/L] vs 3.3 ng/L [IQR: 1.7-6.6 ng/L]; P < 0.001). Troponin concentrations were associated with the primary outcome after adjusting for cardiovascular risk factors and coronary artery disease severity (adjusted HR: 2.3; 95% CI: 1.7-3.0, log10 troponin; P < 0.001). A troponin concentration >10 ng/L identified patients with a 50% increase in the risk of myocardial infarction or cardiovascular death. CONCLUSIONS In patients with chronic coronary artery disease, cardiac troponin predicts risk of myocardial infarction or cardiovascular death independent of cardiovascular risk factors and disease severity. Further studies are required to evaluate whether routine testing could inform the selection of high-risk patients for treatment intensification. (Myocardial Injury in Patients Referred for Coronary Angiography [MICA]; ISRCTN15620297).
Collapse
Affiliation(s)
- Ryan Wereski
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. https://twitter.com/RyanWereski
| | - Philip Adamson
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Nur Shazlin Shek Daud
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Michael McDermott
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Caelan Taggart
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Anda Bularga
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Dorien M Kimenai
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Mathew T H Lowry
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Chris Tuck
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - Atul Anand
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
| | - David J Lowe
- University of Glasgow, School of Medicine, Glasgow, United Kingdom
| | - Andrew R Chapman
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. https://twitter.com/chapdoc1
| | - Nicholas L Mills
- British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom; Usher Institute, University of Edinburgh, Edinburgh, United Kingdom.
| |
Collapse
|
|
8
|
Amrein M, Meier S, Schäfer I, Schaedelin S, Willemse E, Benkert P, Walter J, Puelacher C, Zimmermann T, Median D, Egli C, Leppert D, Twerenbold R, Zellweger M, Kuhle J, Mueller C. Serum neurofilament light chain in functionally relevant coronary artery disease and adverse cardiovascular outcomes. Biomarkers 2023; 28:341-351. [PMID: 36714921 DOI: 10.1080/1354750x.2023.2172211] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Background: Functionally relevant coronary artery disease (fCAD), causing symptoms of myocardial ischemia, can currently only be reliably detected with advanced cardiac imaging. Serum neurofilament light chain (sNfL) is a biomarker for neuro-axonal injury known to be elevated by cardiovascular (CV) risk factors and cerebrovascular small-vessel diseases. Due to their pathophysiological similarities with fCAD and the link to CV risk factors, we hypothesised that sNfL may have diagnostic and prognostic value for fCAD and adverse cardiovascular outcomes.Methods: Of the large prospective Basel VIII study (NCT01838148), 4'016 consecutive patients undergoing cardiac work-up for suspected fCAD were included (median age 68 years, 32.5% women, 46.9% with history of CAD). The presence of fCAD was adjudicated using myocardial perfusion imaging single-photon emission tomography (MPI-SPECT) and coronary angiography. sNfL was measured using a high-sensitive single-molecule array assay. All-cause and cardiovascular death, myocardial infarction (MI), and stroke/transient ischaemic attack (TIA) during 5-year follow-up were the prognostic endpoints.Results: The diagnostic accuracy of sNfL for fCAD as quantified by the area under the curve (AUC) was low (0.58, 95%CI 0.56-0.60). sNfL was strongly associated with age, renal dysfunction, and body mass index and was a strong and independent predictor of all-cause death, cardiovascular death, and stroke/TIA but not MI. Time-dependent AUC for cardiovascular-death at 1-year was 0.85, 95%CI 0.80-0.89, and 0.81, 95%CI 0.77-0.86 at 2-years.Conclusion: While sNfL concentrations did not show a diagnostic role for fCAD, in contrast, sNfL was a strong and independent predictor of cardiovascular outcomes, including all-cause death, cardiovascular death and stroke/TIA.
Collapse
Affiliation(s)
- Melissa Amrein
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Stephanie Meier
- Multiple Sclerosis Centre, Neurology, Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.,Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital and University of Basel, Basel, Switzerland
| | - Ibrahim Schäfer
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Sabine Schaedelin
- Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital and University of Basel, Basel, Switzerland
| | - Eline Willemse
- Multiple Sclerosis Centre, Neurology, Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.,Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital and University of Basel, Basel, Switzerland
| | - Pascal Benkert
- Clinical Trial Unit, Department of Clinical Research, University Hospital Basel, Basel, Switzerland
| | - Joan Walter
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Christian Puelacher
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Tobias Zimmermann
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Daniela Median
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Caroline Egli
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - David Leppert
- Multiple Sclerosis Centre, Neurology, Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.,Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital and University of Basel, Basel, Switzerland
| | - Raphael Twerenbold
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland.,University Center of Cardiovascular Science & Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany
| | - Michael Zellweger
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Jens Kuhle
- Multiple Sclerosis Centre, Neurology, Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.,Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), University Hospital and University of Basel, Basel, Switzerland
| | - Christian Mueller
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland
| |
Collapse
|
|
9
|
Halvorsen S, Mehilli J, Cassese S, Hall TS, Abdelhamid M, Barbato E, De Hert S, de Laval I, Geisler T, Hinterbuchner L, Ibanez B, Lenarczyk R, Mansmann UR, McGreavy P, Mueller C, Muneretto C, Niessner A, Potpara TS, Ristić A, Sade LE, Schirmer H, Schüpke S, Sillesen H, Skulstad H, Torracca L, Tutarel O, Van Der Meer P, Wojakowski W, Zacharowski K. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J 2022; 43:3826-3924. [PMID: 36017553 DOI: 10.1093/eurheartj/ehac270] [Citation(s) in RCA: 388] [Impact Index Per Article: 129.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
|
|
10
|
Williams SA, Ostroff R, Hinterberg MA, Coresh J, Ballantyne CM, Matsushita K, Mueller CE, Walter J, Jonasson C, Holman RR, Shah SH, Sattar N, Taylor R, Lean ME, Kato S, Shimokawa H, Sakata Y, Nochioka K, Parikh CR, Coca SG, Omland T, Chadwick J, Astling D, Hagar Y, Kureshi N, Loupy K, Paterson C, Primus J, Simpson M, Trujillo NP, Ganz P. A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk. Sci Transl Med 2022; 14:eabj9625. [PMID: 35385337 DOI: 10.1126/scitranslmed.abj9625] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
A reliable, individualized, and dynamic surrogate of cardiovascular risk, synoptic for key biologic mechanisms, could shorten the path for drug development, enhance drug cost-effectiveness and improve patient outcomes. We used highly multiplexed proteomics to address these objectives, measuring about 5000 proteins in each of 32,130 archived plasma samples from 22,849 participants in nine clinical studies. We used machine learning to derive a 27-protein model predicting 4-year likelihood of myocardial infarction, stroke, heart failure, or death. The 27 proteins encompassed 10 biologic systems, and 12 were associated with relevant causal genetic traits. We independently validated results in 11,609 participants. Compared to a clinical model, the ratio of observed events in quintile 5 to quintile 1 was 6.7 for proteins versus 2.9 for the clinical model, AUCs (95% CI) were 0.73 (0.72 to 0.74) versus 0.64 (0.62 to 0.65), c-statistics were 0.71 (0.69 to 0.72) versus 0.62 (0.60 to 0.63), and the net reclassification index was +0.43. Adding the clinical model to the proteins only improved discrimination metrics by 0.01 to 0.02. Event rates in four predefined protein risk categories were 5.6, 11.2, 20.0, and 43.4% within 4 years; median time to event was 1.71 years. Protein predictions were directionally concordant with changed outcomes. Adverse risks were predicted for aging, approaching an event, anthracycline chemotherapy, diabetes, smoking, rheumatoid arthritis, cancer history, cardiovascular disease, high systolic blood pressure, and lipids. Reduced risks were predicted for weight loss and exenatide. The 27-protein model has potential as a "universal" surrogate end point for cardiovascular risk.
Collapse
Affiliation(s)
| | | | | | - Josef Coresh
- Johns Hopkins University, Baltimore, MD 21218, USA
| | | | | | - Christian E Mueller
- Cardiovascular Research Institute, University of Basel, Basel 4001, Switzerland
| | - Joan Walter
- Cardiovascular Research Institute, University of Basel, Basel 4001, Switzerland.,Institute of Diagnostic and Interventional Radiology, University Hospital Zürich, University of Zürich, Zürich 7491, Switzerland
| | - Christian Jonasson
- Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim 7491, Norway
| | - Rury R Holman
- Diabetes Trials Unit, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK
| | - Svati H Shah
- Division of Cardiology, Duke Department of Medicine, and Duke Molecular Physiology Institute, Duke University, Durham, NC 27710, USA
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G12 8QQ, UK
| | - Roy Taylor
- Newcastle Magnetic Resonance Centre, University of Newcastle upon Tyne, Newcastle upon Tyne NE1 7RU, UK
| | - Michael E Lean
- School of Medicine, Nursing and Dentistry, University of Glasgow, Glasgow G12 8QQ, UK
| | | | - Hiroaki Shimokawa
- Tohoku University Graduate School of Medicine, Sendai 980-8576, Japan.,Graduate School, International University of Health and Welfare, Narita 286-8686, Japan
| | - Yasuhiko Sakata
- Tohoku University Graduate School of Medicine, Sendai 980-8576, Japan
| | - Kotaro Nochioka
- Tohoku University Graduate School of Medicine, Sendai 980-8576, Japan
| | | | - Steven G Coca
- Mt Sinai Clinical and Translational Science Research Unit, Icahn School of Medicine at Mount Sinai, New York, NY 11766, USA
| | - Torbjørn Omland
- Department of Cardiology, Akershus University Hospital and University of Oslo, Oslo 1478, Norway
| | | | | | | | | | | | | | | | | | | | - Peter Ganz
- Zuckerberg San Francisco General Hospital, University of California, San Francisco, San Francisco, CA 94110, USA
| |
Collapse
|
|
11
|
Walter JE, Amrein MLF, Schäfer I, Zimmermann T, Lopez-Ayala P, Boeddinghaus J, Twerenbold R, Puelacher C, Nestelberger T, Wussler D, Honegger U, Badertscher P, Eugen-Olsen J, Koechlin L, Fahrni G, Jeger R, Kaiser C, Zellweger M, Mueller C. Soluble urokinase plasminogen activator receptor and functionally relevant coronary artery disease: a prospective cohort study. Biomarkers 2022; 27:278-285. [PMID: 35112976 DOI: 10.1080/1354750x.2022.2038269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
BACKGROUND Soluble urokinase plasminogen activator receptor (suPAR) is an emerging biomarker associated with anatomical CAD burden and cardiovascular outcomes including myocardial infarction (MI) and death. We aimed at validating previous findings of the prognostic value of suPAR and evaluated its diagnostic potential for functional relevant CAD (fCAD). METHODS Consecutive patients with suspected fCAD were enrolled. Adjudication of fCAD was performed blinded to suPAR concentrations by myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography. Prognostic outcome measures included all-cause, cardiovascular death, and incident MI during 2-year follow-up. RESULTS Among consecutive 968 patients, SuPAR concentrations were higher in patients with fCAD compared to those without (3.45ng/mL versus 3.20ng/mL, p = 0.007), without acceptable diagnostic accuracy (area under the curve [AUC]: 0.56, 95%CI 0.52-0.60). SuPAR correlated with high-sensitivity cardiac-troponin (hs-cTn) T (Spearman's rho (ρ) 0.393, p < 0.001), NT-proBNP (ρ = 0.327, p < 0.001), age (ρ = 0.364, p < 0.001) and very weakly with coronary atherosclerosis (ρ = 0.123, p < 0.001). Prognostic discrimination of suPAR was moderate for cardiovascular death (AUC =0.72, 95%CI 0.62-0.81) and all-cause death (AUC =0.72, 95%CI 0.65-0.79) at 2-years. SuPAR remained a significant predictor for all-cause death in the full model (HR =1.96, p = 0.001). CONCLUSIONS SuPAR was an independent predictor of all-cause death, without diagnostic utility for fCAD.
Collapse
Affiliation(s)
- Joan Elias Walter
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland.,Department of Radiology, University Hospital Zurich, University of Zurich, Switzerland
| | - Melissa Lee Fen Amrein
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Ibrahim Schäfer
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Tobias Zimmermann
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Pedro Lopez-Ayala
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Jasper Boeddinghaus
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Raphael Twerenbold
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland.,University Heart & Vascular Center Hamburg, Germany
| | - Christian Puelacher
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland.,Department of Radiology, University Hospital Zurich, University of Zurich, Switzerland
| | - Thomas Nestelberger
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland.,Vancouver General Hospital, University of British Columbia, Canada
| | - Desiree Wussler
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland.,Universitäts-Herzzentrum Bad Krozingen, Germany
| | - Ursina Honegger
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Patrick Badertscher
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Jesper Eugen-Olsen
- Clinical Research Centre, Copenhagen University Hospital Hvidovre, Denmark
| | - Luca Koechlin
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland.,Department of Cardiac Surgery, University Hospital Basel, University of Basel, Switzerland
| | - Gregor Fahrni
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Raban Jeger
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Christoph Kaiser
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Michael Zellweger
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| | - Christian Mueller
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Switzerland
| |
Collapse
|
|
12
|
Amrein M, Li XS, Walter J, Wang Z, Zimmermann T, Strebel I, Honegger U, Leu K, Schäfer I, Twerenbold R, Puelacher C, Glarner N, Nestelberger T, Koechlin L, Ceresa B, Haaf P, Bakula A, Zellweger M, Hazen SL, Mueller C. Gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) and cardiovascular risk in patients with suspected functionally relevant coronary artery disease (fCAD). Clin Res Cardiol 2022; 111:692-704. [PMID: 35220448 PMCID: PMC9151506 DOI: 10.1007/s00392-022-01992-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 02/10/2022] [Indexed: 12/29/2022]
Abstract
BACKGROUND Trimethylamine N-oxide (TMAO) has been associated with cardiovascular outcomes. However, the diagnostic value of TMAO and its precursors have not been assessed for functionally relevant coronary artery disease (fCAD) and its prognostic potential in this setting needs to be evaluated. METHODS Among 1726 patients with suspected fCAD serum TMAO, and its precursors betaine, choline and carnitine, were quantified using liquid chromatography tandem mass spectrometry. Diagnosis of fCAD was performed by myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography blinded to marker concentrations. Incident all-cause death, cardiovascular death (CVD) and myocardial infarction (MI) were assessed during 5-years follow-up. RESULTS Concentrations of TMAO, betaine, choline and carnitine were significantly higher in patients with fCAD versus those without (TMAO 5.33 μM vs 4.66 μM, p < 0.001); however, diagnostic accuracy was low (TMAO area under the receiver operating curve [AUC]: 0.56, 95% CI [0.53-0.59], p < 0.001). In prognostic analyses, TMAO, choline and carnitine above the median were associated with significantly (p < 0.001 for all) higher cumulative events for death and CVD during 5-years follow-up. TMAO remained a significant predictor for death and CVD even in full models adjusted for renal function (HR = 1.58 (1.16, 2.14), p = 0.003; HR = 1.66 [1.07, 2.59], p = 0.025). Prognostic discriminative accuracy for TMAO was good and robust for death and CVD (2-years AUC for CVD 0.73, 95% CI [0.65-0.80]). CONCLUSION TMAO and its precursors, betaine, choline and carnitine were significantly associated with fCAD, but with limited diagnostic value. TMAO was a strong predictor for incident death and CVD in patients with suspected fCAD. CLINICAL TRIAL REGISTRATION NCT01838148.
Collapse
Affiliation(s)
- Melissa Amrein
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Xinmin S. Li
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 USA
| | - Joan Walter
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland ,Department of Radiology, University Hospital Zürich, University of Zürich, Zürich, Switzerland
| | - Zeneng Wang
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 USA
| | - Tobias Zimmermann
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland ,Department of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Ivo Strebel
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Ursina Honegger
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Kathrin Leu
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Ibrahim Schäfer
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland ,Department of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Raphael Twerenbold
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Christian Puelacher
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland ,Department of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Noemi Glarner
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Thomas Nestelberger
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland ,Departement of Cardiology, University of British Columbia, Vancouver, Canada
| | - Luca Koechlin
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland ,Department of Cardiac Surgery, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Benjamin Ceresa
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Philip Haaf
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Adam Bakula
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Michael Zellweger
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
| | - Stanley L. Hazen
- Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 USA ,Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195 USA
| | - Christian Mueller
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031, Basel, Switzerland.
| |
Collapse
|
|
13
|
Ramasamy I. Highly sensitive troponin I assay in the diagnosis of coronary artery disease in patients with suspected stable angina. World J Cardiol 2021; 13:745-757. [PMID: 35070116 PMCID: PMC8716973 DOI: 10.4330/wjc.v13.i12.745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/23/2021] [Accepted: 12/03/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Evaluation of suspected stable angina patients with probable coronary artery disease (CAD) in the community is challenging. In the United Kingdom, patients with suspected stable angina are referred by community physicians to be assessed by specialists within the hospital system in rapid access chest pain clinics (RACPC). The role of a highly sensitive troponin I (uscTnI) assay in the diagnosis of suspected CAD in a RACPC in a “real-life” setting in a non-academic hospital has not been explored.
AIM To examine the diagnostic value of uscTnI (detection limit 0.12 ng/L, upper reference range 8.15 ng/L, and detected uscTnI in 96.8% of the reference population), in the evaluation of stable CAD in a non-selected patient group, with several co-morbidities, who presented to the RACPC.
METHODS One hundred and seventy two RACPC patients were assigned to either functional or anatomical testing according to the hospital protocol.
RESULTS The investigations offered to patients were exercise tolerance test 7.6%, 24 h ECG 1.2%, Echocardiogram 14.5%, stress echocardiogram 8.1%, coronary computed tomography angiography (CCTA) 12.8%, coronary angiogram 13.4%, 17.4% were diagnosed with non-cardiac chest pain, 3.5% treated as stable angina, 8.2% reviewed by cardiologists, electronic medical records were not available in 10.4%. Receiver operating characteristic curves for CAD used uscTnI values measured in patients who underwent functional testing, angiogram or CCTA. Values > 0.52 ng/L showed 100% sensitivity and at > 11.6 ng/L showed 100% specificity. In the range > 0.52-11.6 ng/L, uscTnI may not have the same diagnostic potential. In patients assigned to coronary angiogram higher concentrations of uscTnI was associated with severe CAD. Low levels of uscTnI and low pre-test probability of CAD (QRISK3) may decrease patient numbers assigned to CCTA.
CONCLUSION The uscTnI diagnostic cut-off values in a RACPC will depend on patient population and their presenting co-morbidity. In the presence of clinical comorbidities and previous CAD the uscTnI needs to be used in conjunction with clinical assessment.
Collapse
Affiliation(s)
- Indra Ramasamy
- Department of Biochemistry, Worcester Royal Hospital, Worcester WR5 1DD, United Kingdom
| |
Collapse
|
|
14
|
Inconsistent Findings of Cardiac Troponin T and I in Clinical Routine Diagnostics: Factors of Influence. J Clin Med 2021; 10:jcm10143148. [PMID: 34300313 PMCID: PMC8305654 DOI: 10.3390/jcm10143148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/05/2021] [Accepted: 07/14/2021] [Indexed: 11/17/2022] Open
Abstract
Cardiac troponins are crucial for the diagnosis of acute myocardial infarction. Despite known differences in their diagnostic implication, there are no recommendations for only one of the two troponins, cardiac troponin I (cTnI) and troponin T (cTnT) so far. In an everyday routine diagnostic, cTnT (Roche) as well as cTnI (Abbott) were measured in 5667 samples from 3264 patient cases. We investigated the number of identical or discrepant troponin findings. Regarding cTnI, we considered both, sex-dependent and unisex cutoffs. In particular, the number of cTnT positive and cTnI negative results was strikingly high in 14.0% of cTnT positive samples and increases to 23.8% by using sex-specific cTnI cutoffs. This group was considerably greater than the group of cTnI positive and cTnT negative results, also after elimination of patients with an eGFR < 60 mL/min/1.73 m2. Comparing the troponin cases with a dynamic increase or decrease between two measurements, we saw a balanced number of discrepant cases (between cTnT+/cTnI- and cTnT-/cTnI+), which was, however, still present. Using ROC analysis, sex-dependent cutoffs improved sensitivity and specificity of cTnI. This study shows in a large cohort that comparing the two cardiac troponins does not amount to identical analytical results. Consideration of sex-dependent cutoffs may improve sensitivity and specificity.
Collapse
|
|
15
|
Nestelberger T, Boeddinghaus J, Giménez MR, Lopez-Ayala P, Ratmann PD, Badertscher P, Wildi K, Wussler D, Koechlin L, Arslani K, Zimmermann T, Freese M, Rinderknecht T, Miró Ò, Martin-Sanchez FJ, Kawecki D, Geigy N, Keller D, Twerenbold R, Müller C. Direct comparison of high-sensitivity cardiac troponin T and I in the early differentiation of type 1 vs. type 2 myocardial infarction. EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE 2021; 11:62-74. [PMID: 34195803 DOI: 10.1093/ehjacc/zuab039] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/01/2021] [Accepted: 05/19/2021] [Indexed: 11/14/2022]
Abstract
AIMS To directly compare the diagnostic accuracy of high-sensitivity cardiac troponin (hs-cTn) T vs. hs-cTnI in the early non-invasive differentiation of Type 1 myocardial infarction (T1MI) due to plaque rupture and atherothrombosis from Type 2 myocardial infarction (T2MI) due to supply-demand mismatch. METHODS AND RESULTS In a prospective multicentre diagnostic study, two independent cardiologists centrally adjudicated the final diagnosis of T1MI vs. T2MI according to the fourth universal definition of myocardial infarction (MI), using all available clinical information including cardiac imaging in patients presenting with acute chest pain. Diagnostic accuracy was quantified by the area under the receiver operating characteristics curve (AUC). The most extensively validated hs-cTnT-Elecsys and hs-cTnI-Architect assays were measured at presentation, 1 h, and 2 h. Among 5887 patients, 1106 (19%) had a final diagnosis of MI, including 860 (78%) T1MI and 246 (22%) T2MI. The AUC of hs-cTnT-Elecsys to differentiate T1MI from T2MI was moderate and comparable to that provided by hs-cTnI-Architect: hs-cTnT-Elecsys AUC-presentation 0.67 [95% confidence interval (CI) 0.64-0.71], AUC-1 h 0.70 (95% CI 0.66-0.74), and AUC-2 h 0.71 (95% CI 0.66-0.75) vs. hs-cTnI-Architect AUC-presentation 0.71 (95% CI 0.67-0.74), AUC-1 h 0.72 (95% CI 0.68-0.76), and AUC-2 h 0.74 (95% CI 0.69-0.78), all P = not significant (NS). Similarly, the AUC of absolute changes was moderate and comparable for hs-cTnT-Elecsys and hs-cTnI-Architect (all P = NS). Cut-off concentrations achieving at least 90% specificity for the differentiation of T1MI vs. T2MI were >114 ng/L for hs-cTnT-Elecsys [odds ratio (OR) 4.2, 95% CI 2.7-6.6] and >371 ng/L for hs-cTnI-Architect (OR 4.0, 95% CI 2.6-6.2). CONCLUSION hs-cTnT-Elecsys and hs-cTnI-Architect provided comparable, albeit only moderate, diagnostic accuracy for the early differentiation of T1MI vs. T2MI. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov number, NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587.
Collapse
Affiliation(s)
- Thomas Nestelberger
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
- Division of Cardiology, Vancouver General Hospital, University of British Columbia, 899 12th Avenue West, V5Z 1M9 Vancouver BC, Canada
| | - Jasper Boeddinghaus
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
| | - Maria Rubini Giménez
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
- Department of Internal Medicine and Cardiology, Heart Center Leipzig-University Hospital, Strümpellstrasse 39, 04289 Leipzig, Germany
| | - Pedro Lopez-Ayala
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
| | - Paul David Ratmann
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
| | - Patrick Badertscher
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
- Department of Cardiology, Medical University of South Carolina, 179 Ashley Avenue, Charleston, SC, USA
| | - Karin Wildi
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
- Critical Care Research Institute, The Prince Charles Hospital, Brisbane and University of Queensland, 627 Rode Road, Chemside Queensland 4032, Brisbane, Australia
| | - Desiree Wussler
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
| | - Luca Koechlin
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
- Department of Cardiac Surgery, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland
| | - Ketina Arslani
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
| | - Tobias Zimmermann
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
| | - Michael Freese
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
| | - Therese Rinderknecht
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
| | - Òscar Miró
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
- Emergency Department, Hospital Clinic, Barcelona, Villarroel 170, 08036 Barcelona, Spain
| | - F Javier Martin-Sanchez
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
- Servicio de Urgencias, Hospital Clínico San Carlos, Profesor Martin Lagos, 28040, Madrid, Spain
| | - Damian Kawecki
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
- 2nd Department of Cardiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland
| | - Nicolas Geigy
- Emergency Department, Kantonsspital Liestal, Rheinstrasse 26, 4410 Liestal, Switzerland
| | - Dagmar Keller
- Emergency Department, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland
| | - Raphael Twerenbold
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
| | - Christian Müller
- Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland
- GREAT Network, Via Antonio Serra 54, 00191 Rome, Italy
| |
Collapse
|
|
16
|
Walter J, du Fay de Lavallaz J, Koechlin L, Zimmermann T, Boeddinghaus J, Honegger U, Strebel I, Twerenbold R, Amrein M, Nestelberger T, Wussler D, Puelacher C, Badertscher P, Zellweger M, Fahrni G, Jeger R, Kaiser C, Reichlin T, Mueller C. Using High-Sensitivity Cardiac Troponin for the Exclusion of Inducible Myocardial Ischemia in Symptomatic Patients: A Cohort Study. Ann Intern Med 2020; 172:175-185. [PMID: 31905377 DOI: 10.7326/m19-0080] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND The optimal noninvasive method for surveillance in symptomatic patients with stable coronary artery disease (CAD) is unknown. OBJECTIVE To apply a novel approach using very low concentrations of high-sensitivity cardiac troponin I (hs-cTnI) for exclusion of inducible myocardial ischemia in symptomatic patients with CAD. DESIGN Prospective diagnostic cohort study. (ClinicalTrials.gov: NCT01838148). SETTING University hospital. PATIENTS 1896 consecutive patients with CAD referred with symptoms possibly related to inducible myocardial ischemia. MEASUREMENTS Presence of inducible myocardial ischemia was adjudicated using myocardial perfusion imaging with single-photon emission computed tomography, as well as coronary angiography and fractional flow reserve measurements where available. Staff blinded to adjudication measured circulating hs-cTn concentrations. An hs-cTnI cutoff of 2.5 ng/L, derived previously in mostly asymptomatic patients with CAD, was assessed. Predefined target performance criteria were at least 90% negative predictive value (NPV) and at least 90% sensitivity for exclusion of inducible myocardial ischemia. Sensitivity analyses were based on measurements with an hs-cTnT assay and an alternative hs-cTnI assay with even higher analytic sensitivity (limit of detection, 0.1 ng/L). RESULTS Overall, 865 patients (46%) had inducible myocardial ischemia. The hs-cTnI cutoff of 2.5 ng/L provided an NPV of 70% (95% CI, 64% to 75%) and a sensitivity of 90% (CI, 88% to 92%) for exclusion of inducible myocardial ischemia. No hs-cTnI cutoff reached both performance characteristics predefined as targets. Similarly, using the alternative assays for hs-cTnI or hs-cTnT, no cutoff achieved the target performance: hs-cTnT concentrations less than 5 ng/L yielded an NPV of 66% (CI, 59% to 72%), and hs-cTnI concentrations less than 2 ng/L yielded an NPV of 68% (CI, 62% to 74%). LIMITATION Data were generated in a large single-center diagnostic study using central adjudication. CONCLUSION In symptomatic patients with CAD, very low hs-cTn concentrations, including hs-cTnI concentrations less than 2.5 ng/L, do not generally allow users to safely exclude inducible myocardial ischemia. PRIMARY FUNDING SOURCE European Union, Swiss National Science Foundation, Kommission für Technologie und Innovation (Innosuisse), Swiss Heart Foundation, Cardiovascular Research Foundation Basel, University of Basel, University Hospital Basel, Roche, Abbott, and Singulex.
Collapse
Affiliation(s)
- Joan Walter
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Jeanne du Fay de Lavallaz
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Luca Koechlin
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Tobias Zimmermann
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Jasper Boeddinghaus
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Ursina Honegger
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Ivo Strebel
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Raphael Twerenbold
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Melissa Amrein
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Thomas Nestelberger
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Desiree Wussler
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Christian Puelacher
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Patrick Badertscher
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland, and University of Illinois at Chicago, Chicago, Illinois (P.B.)
| | - Michael Zellweger
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Gregor Fahrni
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Raban Jeger
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Christoph Kaiser
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| | - Tobias Reichlin
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, and University Hospital Bern, University of Bern, Bern, Switzerland (T.R.)
| | - Christian Mueller
- Cardiovascular Research Institute Basel, University Hospital Basel, and University of Basel, Basel, Switzerland (J.W., J.D., L.K., T.Z., J.B., U.H., I.S., R.T., M.A., T.N., D.W., C.P., M.Z., G.F., R.J., C.K., C.M.)
| |
Collapse
|
|
17
|
Honegger U, Walter JE, Mueller D, Puelacher C, Schaerli N, Twerenbold R, Badertscher P, Boeddinghaus J, Nestelberger T, du Fay de Lavallaz J, Wussler D, Pfister O, Jeger R, Kaiser C, Wild D, Schmidt-Trucksäss A, Reichlin T, Mueller C. Prevalence and determinants of exercise-induced left ventricular dysfunction in patients with coronary artery disease. Eur J Clin Invest 2019; 49:e13112. [PMID: 30925205 DOI: 10.1111/eci.13112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 02/28/2019] [Accepted: 03/21/2019] [Indexed: 01/24/2023]
Abstract
BACKGROUND The phenomenon of exercise-induced left ventricular dysfunction (LVD) is incompletely understood. Better understanding of its prevalence and determinants might help to address the current potential oversimplification of the relation between physical activity and cardiac health in patients with coronary artery disease (CAD). METHODS We prospectively assessed the prevalence and determinants of exercise-induced LVD in patients with stable CAD and normal LV function at rest undergoing bicycle rest/stress myocardial perfusion imaging single-photon emission computed tomography (MPI-SPECT). Exercise-induced LVD was defined as a relevant (5% or more) drop in left ventricular ejection fraction after maximal exercise. High-sensitivity cardiac troponin I/T (Hs-cTnI/T) and N-terminal probrain natriuretic peptide (NT-proBNP) concentrations were measured before exercise to quantify cardiomyocyte injury and hemodynamic cardiac stress, respectively. RESULTS Among 317 patients, exercise-induced LVD was present in 83 (26%) patients. Exercise-induced LVD was associated with the extent of exercise-inducible myocardial ischaemia as well as transient ischaemic dilatation. Still, 43% of patients developing exercise-induced LVD did not have functionally relevant CAD. Neither baseline characteristics, nor the quantification of the extent of cardiomyocyte injury and hemodynamic cardiac stress using hs-cTnI/T and NT-proBNP concentrations, respectively, allowed predicting exercise-induced LVD. CONCLUSION One out of four patients with stable CAD develops exercise-induced LVD after bicycle exercise test. While the extent of exercise-inducible myocardial ischaemia is a predictor, other still unrecognized mechanisms also seem to play a major role, as nearly half of all patients with exercise-induced LVD do not have functionally relevant CAD.
Collapse
Affiliation(s)
- Ursina Honegger
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Joan E Walter
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Deborah Mueller
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Christian Puelacher
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland.,Division of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Nicolas Schaerli
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland.,Division of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Raphael Twerenbold
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland.,Department of General and Interventional Cardiology, University Heart Center Hamburg, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Patrick Badertscher
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Jasper Boeddinghaus
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland.,Division of Internal Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Thomas Nestelberger
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Jeanne du Fay de Lavallaz
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Desiree Wussler
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Otmar Pfister
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Raban Jeger
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Christoph Kaiser
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Damian Wild
- Division of Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | | | - Tobias Reichlin
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| | - Christian Mueller
- Department of Cardiology, Cardiovascular Research Institute Basel (CRIB), University Hospital Basel, University of Basel, Basel, Switzerland
| |
Collapse
|
|
18
|
Can Biomarkers of Myocardial Injury Provide Complementary Information to Coronary Imaging? JACC Cardiovasc Imaging 2019; 12:1117-1119. [DOI: 10.1016/j.jcmg.2019.05.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
|
|
19
|
Cwikiel J, Seljeflot I, Fagerland MW, Wachtell K, Arnesen H, Berge E, Flaa A. High-sensitive cardiac Troponin T and exercise stress test for evaluation of angiographically significant coronary disease. Int J Cardiol 2019; 287:1-6. [PMID: 31006595 DOI: 10.1016/j.ijcard.2019.04.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2018] [Revised: 04/02/2019] [Accepted: 04/05/2019] [Indexed: 11/16/2022]
Abstract
BACKGROUND Exercise stress test (EST) has a moderate precision for diagnosis of CAD and could potentially obtain improved accuracy if adding a reliable cardiac biomarker to the test. OBJECTIVE We aimed to investigate resting levels and change in hs-cTnT during EST in patients with and without angiographically significant CAD. Moreover, we intended to explore the additive value of hs-cTnT to EST results in diagnosis of stable CAD. We hypothesized that hs-cTnT would be higher in CAD patients and increase diagnostic precision of EST. METHOD Patients presenting with symptoms of stable CAD, performed a maximal EST on a bicycle ergometer. Venous blood samples were taken at rest and within 5 min post-exercise. All patients underwent coronary angiography. Significant CAD was defined as having ≥75% stenosis in one or more segments of the coronary arteries. RESULTS Out of the 297 participants, significant CAD was found in 111 (37%) patients. Patients with significant CAD compared to without, had higher resting levels of hs-cTnT (median 8.1 vs 5.0 ng/L) and no significant difference in exercise-induced change (median 0.5 vs 0.3 ng/L), p < 0.001 and p = 0.086 respectively. Combined resting hs-cTnT with EST had higher predictive value for significant CAD than EST alone, AUC = 0.751 vs. AUC = 0.637. In an adjusted multivariable regression analysis, resting hs-cTnT >6.0 ng/L was predictive for having significant CAD, OR 2.55 (CI 95% 1.40, 4.65 p = 0.002). CONCLUSION In patients with suspected stable CAD, hs-cTnT has a predictive value alone, as well as added to a diagnostic EST for CAD.
Collapse
Affiliation(s)
- Joanna Cwikiel
- Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevaal, Norway; Faculty of Medicine, University of Oslo, Norway; Section of Cardiovascular and Renal Research Oslo University Hospital Ullevaal, Norway.
| | - Ingebjørg Seljeflot
- Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevaal, Norway; Department of Cardiology, Oslo University Hospital Ullevaal, Norway; Faculty of Medicine, University of Oslo, Norway.
| | - Morten W Fagerland
- Oslo Centre for Biostatistics and Epidemiology, Research Support Service, Oslo University Hospital, Oslo, Norway.
| | - Kristian Wachtell
- Department of Cardiology, Section for Cardiology Intervention, Division of Cardiovascular and Pulmonary Diseases, Oslo University Hospital, Norway.
| | - Harald Arnesen
- Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ullevaal, Norway; Faculty of Medicine, University of Oslo, Norway.
| | - Eivind Berge
- Department of Cardiology, Oslo University Hospital Ullevaal, Norway.
| | - Arnljot Flaa
- Department of Cardiology, Oslo University Hospital Ullevaal, Norway; Section of Cardiovascular and Renal Research Oslo University Hospital Ullevaal, Norway
| |
Collapse
|
|
20
|
Cardiac Troponin in Stable Chest Pain. J Am Coll Cardiol 2019; 73:2120-2121. [DOI: 10.1016/j.jacc.2019.02.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 02/19/2019] [Indexed: 11/20/2022]
|
|
21
|
Adamson PD, Mills NL. High-Sensitivity Troponin and the Selection of Patients for Cardiac Imaging in the Outpatient Clinic. Clin Chem 2018; 64:1555-1557. [PMID: 30237147 DOI: 10.1373/clinchem.2018.294629] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Accepted: 09/04/2018] [Indexed: 11/06/2022]
Affiliation(s)
- Philip D Adamson
- BHF Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom.,Christchurch Heart Institute, University of Otago, Christchurch, New Zealand
| | - Nicholas L Mills
- BHF Centre for Cardiovascular Research, University of Edinburgh, Edinburgh, United Kingdom; .,Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom
| |
Collapse
|