Prognostic Value of Cardiac Magnetic Resonance Tissue Characterization in Risk Stratifying Patients With Suspected Myocarditis

Abstract

Background: Diagnosing myocarditis is challenged by nonspecific clinical signs and symptoms and low accuracy of endomyocardial biopsy. Cardiac magnetic resonance imaging (CMR) provides both cardiac anatomy and tissue characterization in this setting, but the prognostic value of this method as a primary assessment tool in patients with suspected myocarditis remains limited.

Objectives: This study sought to determine cardiac event-free survival of a consecutive cohort with suspected myocarditis with regard to CMR findings.

Methods: Six hundred seventy patients with suspected myocarditis underwent CMR including late gadolinium enhancement (LGE) parameters between 2002 and 2015 and were included and followed. We performed multivariable model for major adverse cardiovascular events (MACE) and determined the continuous net reclassification improvement by LGE markers.

Results: At a median follow-up of 4.7 years (interquartile range [IQR]: 2.3 to 7.3 years), 98 patients experienced a MACE. Two hundred ninety-four (44%) patients showed LGE presence, which was associated with a more than doubling risk of MACE (hazard ratio [HR]: 2.22; 95% confidence interval [CI]: 1.47 to 3.35; p < 0.001). Annualized MACE rates were 4.8% and 2.1% corresponding to LGE presence and absence, respectively (p < 0.001). In the multivariable model, LGE presence maintained significant association with MACE (HR: 1.72; 95% CI: 1.08 to 2.76; p = 0.023). The computed continuous net reclassification improvement was 0.39 (95% CI: 0.10 to 0.67) when LGE presence was added to the multivariable model for MACE. Regarding location and pattern, septal and midwall LGE showed strongest associations with MACE (HR: 2.55; 95% CI: 1.77 to 3.83 and HR: 2.39; 95% CI: 1.54 to 3.69, respectively; both p < 0.001). A patchy distribution portended to a near 3-fold increased hazard to MACE (HR: 2.93; 95% CI: 1.79 to 4.80; p < 0.001). LGE extent (per 10% increase) corresponded to a 79% increase in risk of MACE (HR: 1.79; 95% CI: 1.25 to 2.57; p = 0.002). A normal CMR study corresponded to low annual MACE and death rates of 0.8% and 0.3%, respectively.

Conclusions: CMR tissue characterization provides effective risk stratification in patients with suspected myocarditis.

Keywords: CMR; cardiovascular magnetic resonance imaging; extracellular volume; myocarditis; outcome.

FIGURE 1. Examples of Different LGE Distributions and Patterns Seen in the Cohort

(A) Patient #1. A short-axis view is displayed with a patchy LGE distribution and an epicardial and midwall pattern, which can also be depicted in the same patient in a 4-chamber view (B). (C) Patient #2. The short-axis image showing LGE presence in anterolateral, inferolateral, and inferior locations, in a linear distribution and a mostly midwall pattern. (D, E) Patient #3. A patchy distribution with midwall pattern located in the septum is shown in a short-axis view, which was confirmed by a 4-chamber view (E). (F) Patient #4. A diffuse LGE distribution, mainly in the midwall. White arrows describe LGE. LGE = late gadolinium enhancement.

FIGURE 2

Consort Diagram of Patient Enrollment

FIGURE 3. Annualized Event Rates Between LGE Presence and LGE Absence in Patients With Suspected Myocarditis

There are significant differences between the annualized event rates for MACE and death between patients with suspected myocarditis and LGE presence versus those without LGE. LGE = late gadolinium enhancement; MACE = major adverse cardiac event(s).

FIGURE 4. The Event-Free (MACE) Survival Probability Curve of Patients With Suspected Myocarditis and Combination of LGE Presence and LVEF Are Displayed

Patients with LVEF ≥40% and LGE absence have a significantly better prognosis compared to those with LVEF ≥40% and LGE presence. However, patients with LVEF <40% and LGE absence or presence have the worst outcome compared to those with LVEF ≥40%. LVEF = left ventricular ejection fraction; other abbreviations as in Figures 1 and 3.

FIGURE 5. Annualized Event Rates Between LGE Presence and LGE Absence and LVEF in Patients With Suspected Myocarditis

There are significant differences between the annualized event rates for MACE and death between patients with suspected myocarditis and LVEF ≥40% with LGE presence versus those without LGE. In patients with suspected myocarditis and LVEF <40%, annualized event rates for MACE and death were not significantly different between patients with LGE present versus patients without LGE. Abbreviations as in Figures 1, 3, and 4..

CENTRAL ILLUSTRATION. Patient With Suspected Myocarditis Who Was Referred for CMR Evaluation and Event-Free Survival Probability Curve

This is a case of a 20-year-old male without prior cardiac history who was referred for CMR with suspected myocarditis. The patient presented with chest pain, electrocardiogram changes with inferior ST-segment elevations, elevated troponin, and no angiographically significant coronary artery disease. No recent viral or other illness was known and the patient did not take any medication nor was there illegal substance abuse. EMB was not performed. CMR showed linear, epicardial LGE (A) in the anterior, anterolateral, and inferior/inferolateral segments (white arrows). LGE extent was measured using the FWHM quantification method with an ROI 1 placed in the identified affected myocardium (pink arrow/pink contour). LGE extent presented to be 15.6% (B). On T2-weighted imaging there is increased signal in the same segments where LGE was present (C, white arrows). Signal intensity (SI) ratio of myocardium/skeletal muscle (D, ROI 2 with brown arrow/brown contour) indicates edema in the affected segments with SI ratio being ≥2.0. (E) The event-free (MACE) survival probability curve of patients with suspected myocarditis showed that patients with LGE presence had a significantly worse outcome compared to those without LGE. CMR = cardiac magnetic resonance imaging; EMB = endomyocardial biopsy; FWHM = full width half maximum; LGE = late gadolinium enhancement; MACE = major adverse cardiovascular event; ROI = region of interest..