Splenic switch-off in three-dimensional adenosine stress cardiac magnetic resonance perfusion for differentiating true-negative from potentially false-negative studies identified by fractional flow reserve

Journal of Cardiovascular Magnetic Resonance, vol. 27, pp. 101933

Abstract

False-negative cardiovascular magnetic resonance (CMR) perfusion results may arise from inadequate stress responses, even when patients exhibit an adequate clinical or heart-rate response to adenosine. This study aimed to explore the ability of qualitative and quantitative splenic switch-off (SSO) markers to differentiate true-negative from potentially false-negative adenosine stress-perfusion CMR findings in a cohort where fractional flow reserve (FFR) was used to adjudicate lesion significance. Patients with known or suspected coronary artery disease (CAD) from five centers underwent three-dimensional (3D) adenosine stress perfusion CMR and coronary angiography with FFR. SSO was assessed qualitatively using both standard stress-to-rest (SSO) and a stress-only (SSO stress ) approach. In addition, quantitative signal intensity (SI) ratios were assessed, including the splenic stress-to-rest SI-ratio (SI stress/rest ) and the spleen-to-myocardium SI ratio at stress (SI spleen/myocarcium ). The diagnostic accuracy of these measures was evaluated using cross-validated area under the curve (cvAUC) analysis. Among 179 patients (mean age 63 ± 10 years; 130 male), SSO prevalence was 73% (130/179) and was significantly more frequent in true-negative than false-negative CMR cases (80.6% [54/67] vs 36.8% [7/19], p < 0.001). SSO stress showed moderate agreement (κ = 0.60) and robust diagnostic performance (AUC 0.80), as compared to SSO. Splenic SI stress/rest and SI spleen/myocarcium at stress demonstrated high predictive accuracy for visual SSO, with cvAUCs of 0.94 (95% CI: 0.90–0.96) and 0.90 (95% CI: 0.86–0.95), respectively. The positive likelihood ratio of SSO for true-negative CMR was 1.70, while the negative likelihood ratio was 0.24. Qualitative and quantitative splenic-switch off metrics classified 77%–80% (66-69/86) of negative CMR cases correctly as true- or potentially false-negatives, with sensitivities ranging from 81.4% to 91.2%. Clinically applicable cut-offs for differentiating true- and false-negative studies with splenic SI stress/rest and SI spleen/myocarcium at stress were identified as ≤0.32 and ≤0.38, respectively. In a multicenter cohort using FFR-adjudicated reference for lesion severity, qualitative SSO and quantitative SI metrics were associated with myocardial stress adequacy and these markers may improve the interpretation of negative stress-perfusion CMR studies.

Authors 13

1. Mihály Károlyi

   University of Zurich · University Hospital Zurich

   Affiliation as printed

   Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland

   Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, University of Zurich, Switzerland; Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland

2. Maximilian Füetterer

   ETH Zurich · Institute for Biomedical Engineering

   Affiliation as printed

   Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

   Institute for Biomedical engineering, University and ETH Zurich, Switzerland

3. Márton Kolossváry

   Gottsegen National Cardiovascular Center · Obuda University

   Affiliation as printed

   Gottsegen National Cardiovascular Center, Budapest, Hungary; Physiological Controls Research Center, University Research and Innovation Center, Óbuda University, Budapest, Hungary

4. Verena Wilzeck

   University of Zurich · ETH Zurich · University Hospital Zurich · Institute for Biomedical Engineering

   Affiliation as printed

   Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

   Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, University of Zurich, Switzerland; Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Institute for Biomedical engineering, University and ETH Zurich, Switzerland

5. Sven Plein

   University of Leeds

   Affiliation as printed

   Multidisciplinary Cardiovascular Research Centre and the Department of Biomedical Imaging, Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

   Multidisciplinary Cardiovascular Research Centre & the Department of Biomedical Imaging, Science, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK

6. Alexander Gotschy

   University of Zurich · ETH Zurich · University Hospital Zurich · Institute for Biomedical Engineering

   Affiliation as printed

   Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

   Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, University of Zurich, Switzerland; Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Institute for Biomedical engineering, University and ETH Zurich, Switzerland

7. Michael Frick Aachen Department of Internal Medicine I (Cardiology)

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Department of Internal Medicine I, Cardiology, Angiology and Internal Intensive Care Medicine, University Hospital RWTH Aachen University, Aachen, Germany

   Department of Internal Medicine I, Cardiology, Angiology and Internal Intensive Care Medicine, University hospital RWTH Aachen University, Aachen, Germany

8. Rolf Gebker
   Affiliation as printed

   MVZ Diagnostikum Berlin 2020 GmbH, Berlin, Germany

9. Hatem Alkadhi

   University of Zurich · University Hospital Zurich

   Affiliation as printed

   Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

   Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, University of Zurich, Switzerland

10. Ingo Paetsch

    Leipzig University

    Affiliation as printed

    Department of Electrophysiology, HELIOS Heart Center Leipzig at University of Leipzig, Leipzig, Germany

11. Cosima Jahnke

    Leipzig University

    Affiliation as printed

    Department of Electrophysiology, HELIOS Heart Center Leipzig at University of Leipzig, Leipzig, Germany

12. Sebastian Kozerke

    ETH Zurich · Institute for Biomedical Engineering

    Affiliation as printed

    Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland

    Institute for Biomedical engineering, University and ETH Zurich, Switzerland

13. Robert Manka corresponding

    University of Zurich · ETH Zurich · University Hospital Zurich · Institute for Biomedical Engineering

    Affiliation as printed

    Diagnostic and Interventional Radiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland. Electronic address: Robert.Manka@usz.ch

    Diagnostic and Interventional Radiology, University Hospital Zurich, Zurich, University of Zurich, Switzerland; Department of Cardiology, University Heart Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Institute for Biomedical engineering, University and ETH Zurich, Switzerland. Electronic address: Robert.Manka@usz.ch