Splenic Switch-Off in 3D Adenosine Stress CMR Perfusion for Differentiating False-Negative from True-Negative Studies Identified by FFR.

Abstract

Background: False-negative cardiac 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 markers to differentiate false-negative from true-negative adenosine stress-perfusion CMR findings, in a cohort where fractional flow reserve (FFR) was used to adjudicate lesion significance.

Methods: Patients with known or suspected coronary artery disease (CAD) from five centers underwent 3D adenosine stress perfusion CMR and coronary angiography with FFR. Splenic switch-off 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.

Results: Among 179 patients (mean age 63 ± 10 years; 130 male), SSO prevalence was 73% and was significantly more frequent in true-negative than false-negative CMR cases (80.6% vs. 36.8%, 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, indicating false-negative CMR when SSO was absent. Qualitative and quantitative splenic-switch off metrics classified 77-80% of negative CMR cases correctly as true- or 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.

Conclusion: In a multicenter cohort using FFR-adjudicated reference for lesion severity, qualitative SSO and quantitative signal intensity metrics were associated with myocardial stress adequacy and these markers may improve the interpretation of negative stress-perfusion CMR studies.