Comparison of myocardial fibrosis quantification methods by cardiovascular magnetic resonance imaging for risk stratification of patients with suspected myocarditis

Abstract

Background: Although the presence of late gadolinium enhancement (LGE) using cardiovascular magnetic resonance imaging (CMR) is a significant discriminator of events in patients with suspected myocarditis, no data are available on the optimal LGE quantification method.

Methods: Six hundred seventy consecutive patients (48 ± 16 years, 59% male) with suspected myocarditis were enrolled between 2002 and 2015. We performed LGE quantitation using seven different signal intensity thresholding methods based either on 2, 3, 4, 5, 6, 7 standard deviations (SD) above remote myocardium or full width at half maximum (FWHM). In addition, a LGE visual presence score (LGE-VPS) (LGE present/absent in each segment) was assessed. For each of these methods, the strength of association of LGE results with major adverse cardiac events (MACE) was determined. Inter-and intra-rater variability using intraclass-correlation coefficient (ICC) was performed for all methods.

Results: Ninety-eight (15%) patients experienced a MACE at a medium follow-up of 4.7 years. LGE quantification by FWHM, 2- and 3-SD demonstrated univariable association with MACE (hazard ratio [HR] 1.05, 95% confidence interval [CI]:1.02-1.08, p = 0.001; HR 1.02, 95%CI:1.00-1.04; p = 0.001; HR 1.02, 95%CI: 1.00-1.05, p = 0.035, respectively), whereas 4-SD through 7-SD methods did not reach significant association. LGE-VPS also demonstrated association with MACE (HR 1.09, 95%CI: 1.04-1.15, p < 0.001). In the multivariable model, FWHM, 2-SD methods, and LGE-VPS each demonstrated significant association with MACE adjusted to age, sex, BMI and LVEF (adjusted HR of 1.04, 1.02, and 1.07; p = 0.009, p = 0.035; and p = 0.005, respectively). In these, FWHM and LGE-VPS had the highest degrees of inter and intra-rater reproducibility based on their high ICC values.

Conclusions: FWHM is the optimal semi-automated quantification method in risk-stratifying patients with suspected myocarditis, demonstrating the strongest association with MACE and the highest technical consistency. Visual LGE scoring is a reliable alternative method and is associated with a comparable association with MACE and reproducibility in these patients.

Trial registration number: NCT03470571 . Registered 13th March 2018. Retrospectively registered.

Keywords: CMR; Cardiovascular magnetic resonance imaging; FWHM; Full width half maximum; MACE; Myocarditis; Outcome; Quantification method; SD; Standard deviation.

Conflict of interest statement

Ethics approval and consent to participate

All study procedures were reviewed and approved by our Institutional Review Board at Brigham and Women’s Hospital, Harvard Medical School Boston in accordance with institutional guidelines. Given the retrospective nature of the current data spanning the past decade, obtaining informed consent from each patient was not logistically feasible, and a waiver for signing informed consent was obtained from by our Institutional Review Board. For patients who were followed-up by email or phone, signed informed consent is available.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Example of the different late gadolinium enhancement (LGE) quantification methods in a patient with suspected myocarditis. a LGE-image with endocardium and epicardium is demarcated, b 2-SD (LGE: 28.9 g, 24.9% of total left ventricular (LV) mass); c 3-SD (19.4g, 16.8%); d 4-SD (12.2 g, 10.5%); e 5-SD (8.1g, 7.0%); f 6-SD (5.2 g, 4.5%); g 7-SD (3.3 g, 2.9%); h full width half maximum (FWHM) (14.7 g, 12.6%). Total LV mass was 116 g. The fibrosis is outlined in yellow. For 2 to 7-SD a region of interest (ROI) 1 is identified in the reference remote myocardium (yellow arrow/yellow contour). For FWHM, an automated ROI 2 is identified in the affected myocardium (pink arrow/pink contour). Of note, only the midventricular slice is represented, however, total LGE quantification includes mass and percentage of the entire left ventricle. SD = standard deviation

Fig. 2

Difference in LGE mass (%) between different semi-automated quantification methods in LGE positive cases are displayed. Comparing the different semi-quantitative LGE quantification methods, the greatest amount of LGE was measured with the 2-SD method and lowest with the 7-SD method. Confidence intervals were broader in lower SD methods. LGE = Late gadolinium enhancement, FWHM = Full width at half maximum, SD = Standard deviation

Fig. 3

Univariable association of different semi-automated LGE (%) quantification methods with outcome. Comparing the different semi-quantitative LGE quantification methods, only 2-SD, 3-SD and FWHM were significantly associated with MACE. LGE = Late gadolinium enhancement, FWHM = Full width at half maximum, SD = Standard deviation, MACE = Major adverse cardiovascular event, HR = Hazard ratio, CI = Confidence interval

Fig. 4

Reproducibility of different LGE quantification methods. Intra-rater and inter-rater variability for each LGE quantification method (calculated as 1 - intraclass correlation coefficient [ICC]) of the different methods is lowest in visual scores and FWHM. Intra-rater variability is less marked than inter-rater variability, as would be expected. Of the quantifications methods significantly associated with MACE, FWHM, LGE-VPS and LGE-VTS showed the best inter- and intra-rater variability. FWHM = Full width half maximum, SD = Standard deviation; LGE-VPS = visual LGE presence score; LGE-VTS = visual LGE transmurality score; MACE = Major adverse cardiovascular event