Imaging of Clinically Unrecognized Myocardial Fibrosis in Patients With Suspected Coronary Artery Disease

Abstract

Background: Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia.

Objectives: This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia.

Methods: In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE).

Results: UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p < 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p < 0.001), statin (p < 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p < 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p < 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p < 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE.

Conclusions: In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891).

Keywords: coronary artery disease; secondary prevention; silent myocardial infarction; stress cardiac magnetic resonance; unrecognized myocardial infarction.

Copyright © 2020 American College of Cardiology Foundation. All rights reserved.

Figures

Central Illustration.

Time-to-Event Curves for Death and/or MI and MACE. Time-to-event curves for death and/or myocardial infarction (MI) (top) and major adverse cardiac events (MACE) (bottom). Event-free survival for patients with recognized myocardial infarction (RMI), unrecognized myocardial infarction (UMI), and neither form of MI are shown in black, red, and blue respectively. Statistical analysis using log-rank test for “no MI versus MI” and “unrecognized MI versus recognized MI.” CI = confidence interval.

Figure 1.

Use of Cardiovascular Medications in the Study Population. Treatment rates for aspirin, statin, beta-blocker, angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) and diuretics according to the presence or absence of myocardial infarction (MI)—unrecognized myocardial infarction (UMI) or recognized myocardial infarction (RMI). N = 2,349.

Figure 2.

Time-to-Event Curves for Death and/or MI and MACE in Patients Without Ischemia on Stress CMR Time-to-event curves for death and/or MI (top) and major adverse cardiac events (MACE) (bottom) in patients without ischemia on stress cardiac magnetic resonance (CMR). Event-free survival for patients with RMI, UMI, and neither form of MI are shown in black, red, and blue respectively. Statistical analysis using log-rank test for “no MI versus MI” and “UMI versus RMI.” CI = confidence interval; other abbreviations as in Figure 1.