Sung-Ji Park MD, PhD^a,*, Sung Woo Cho MD, PhD^b,*, Sung Mok Kim MD, PhD^c, Joonghyun Ahn MS^d, Keumhee Carriere PhD^{d, e}, Dong Seop Jeong MD, PhD^f, Sang-Chol Lee MD, PhD^a, Seung Woo Park MD, PhD^a, Yeon Hyeon Choe MD, PhD^c, Pyo Won Park MD, PhD^f, Jae K. Oh MD<sup>a, g

a</sup> Department of Medicine, Division of Cardiology, Cardiovascular Imaging Center, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
^b Department of Medicine, Division of Cardiology, Inje University College of Medicine, Seoul Paik Hospital, Seoul, Republic of Korea
^c Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
^d Biostatistics and Clinical Epidemiology Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Republic of Korea
^e Department of Mathematical and Statistical Sciences, University of Alberta, Edmonton, Alberta, Canada
^f Department of Thoracic Surgery, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
^g Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota

^*Drs. Park and Cho contributed equally to this work and are joint first authors.

Addresses for correspondence:
Dr. Sung-Ji Park, Division of Cardiology, Department of Internal Medicine, Cardiovascular Imaging Center, Heart Vascular Stroke Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.

Dr. Sung Mok Kim, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81, Irwon-ro, Gangnam-gu, Seoul 06351, Republic of Korea.

Objectives
This study assessed diffuse myocardial fibrosis (MF) by cardiac magnetic resonance (CMR) imaging and speckle-tracking echocardiography (STE) in patients with severe aortic stenosis (AS) and validated findings by using histologic confirmation of MF.

Background
MF is a concomitant pathologic finding related to hypertrophic response in severe AS. It would be beneficial to have reliable imaging methods to assess MF.

Methods
CMR and STE were performed in 71 consecutive patients with severe AS before aortic valve replacement. The extracellular volume (ECV) and native T1 values obtained by CMR and global longitudinal strain (GLS) values by STE were measured. The degree of MF was quantified by using Masson trichrome stain in myocardial biopsy specimens obtained intraoperatively. The study population was divided into 3 groups according to the degree of MF on histology (mild, moderate, and severe MF).

Results
The severe MF group had a higher incidence of heart failure (HF) and diastolic dysfunction than the mild and moderate MF groups. The ECV (r = 0.465; p < 0.0001), GLS (r = 0.421; p = 0.0003), and native T1 (r = 0.429; p = 0.0002) values were significantly correlated with the degree of MF. GLS was moderately correlated with ECV (r = 0.455; p = 0.0001) and less with the native T1 (r = 0.372; p = 0.0014) value. The model using ECV (R2 = 0.44; Akaike Information Criterion [AIC] = 55.8) was found to predict the degree of MF most accurately than that with GLS (R² = 0.35; AIC = 66.84) and the native T1 (R² = 0.36; AIC = 66.18) value. The secondary endpoint of interest was clinical outcome of a composite of total mortality, admission for HF, or development of HF symptoms. During follow-up (median: 4.6 years), and there were 16 clinical events. Although statistically insignificant, ECV is more closely related to prediction of the clinical outcome than native T1 or GLS.

Conclusions
ECV as assessed by CMR could be an ideal surrogate marker for diffuse MF in patients with severe AS among all 3 models considered.

Key Words : extracellular volume; global longitudinal strain; myocardial fibrosis; severe aortic stenosis