Extracellular Myocardial Volume in Patients With Aortic Stenosis

Abstract

Background: Myocardial fibrosis is a key mechanism of left ventricular decompensation in aortic stenosis and can be quantified using cardiovascular magnetic resonance (CMR) measures such as extracellular volume fraction (ECV%). Outcomes following aortic valve intervention may be linked to the presence and extent of myocardial fibrosis.

Objectives: This study sought to determine associations between ECV% and markers of left ventricular decompensation and post-intervention clinical outcomes.

Methods: Patients with severe aortic stenosis underwent CMR, including ECV% quantification using modified Look-Locker inversion recovery-based T1 mapping and late gadolinium enhancement before aortic valve intervention. A central core laboratory quantified CMR parameters.

Results: Four-hundred forty patients (age 70 ± 10 years, 59% male) from 10 international centers underwent CMR a median of 15 days (IQR: 4 to 58 days) before aortic valve intervention. ECV% did not vary by scanner manufacturer, magnetic field strength, or T1 mapping sequence (all p > 0.20). ECV% correlated with markers of left ventricular decompensation including left ventricular mass, left atrial volume, New York Heart Association functional class III/IV, late gadolinium enhancement, and lower left ventricular ejection fraction (p < 0.05 for all), the latter 2 associations being independent of all other clinical variables (p = 0.035 and p < 0.001). After a median of 3.8 years (IQR: 2.8 to 4.6 years) of follow-up, 52 patients had died, 14 from adjudicated cardiovascular causes. A progressive increase in all-cause mortality was seen across tertiles of ECV% (17.3, 31.6, and 52.7 deaths per 1,000 patient-years; log-rank test; p = 0.009). Not only was ECV% associated with cardiovascular mortality (p = 0.003), but it was also independently associated with all-cause mortality following adjustment for age, sex, ejection fraction, and late gadolinium enhancement (hazard ratio per percent increase in ECV%: 1.10; 95% confidence interval [1.02 to 1.19]; p = 0.013).

Conclusions: In patients with severe aortic stenosis scheduled for aortic valve intervention, an increased ECV% is a measure of left ventricular decompensation and a powerful independent predictor of mortality.

Keywords: T1 mapping; aortic stenosis; cardiovascular magnetic resonance; diffuse myocardial fibrosis.

Graphical abstract

Figure 1

Flow Diagram of Study Participants CMR = cardiovascular magnetic resonance; SAVR = surgical aortic valve replacement; TAVR = transcatheter aortic valve replacement.

Figure 2

Multiparametric CMR Assessment Cardiovascular magnetic resonance (CMR) short-axis cine images were contoured to provide ventricular volumes, mass, and ejection fraction (A). Areas of late gadolinium enhancement (B, red arrows) were quantified using the full-width-at-half-maximum technique. Native (C) and post-contrast (D) T1 maps were analyzed, and the mean value from segment 9 (shaded blue) and blood pool (orange contour) were used to calculate the extracellular volume fraction (ECV%). ECV% values did not vary by field strength (p = 0.98) (F), and minimal variation in ECV% values was observed across the different centers (G). By contrast, native T1 values varied significantly by center (H), mainly due to the effect of magnetic field strength (blue = 1.5-T, red = 3.0-T). Contour legend: red = left ventricular endocardial; green = left ventricular epicardial; yellow = right ventricular endocardial; purple = papillary muscle; orange = blood pool region of interest; blue = myocardial (segment 9) region of interest. AMC = Asan Medical Center, Seoul, Korea; BER = Berlin, Germany; BHC = Barts Heart Centre, London, United Kingdom; EDI = Edinburgh, United Kingdom; GLE = Leicester, United Kingdom; LGI = Leeds, United Kingdom; ORH = Oxford, United Kingdom; QUE = Québec, Canada; Sh = ShMOLLI T1 mapping sequence used; SNUH = Seoul National University Hospital, Seoul, Korea; UPMC = Pittsburgh, Pennsylvania.

Figure 3

Markers of LV Decompensation Across ECV% and iECV Tertiles When comparing clinical and imaging variables across extracellular volume fraction (ECV%) tertiles, there was a progressive increase in LV mass (A), LV end-diastolic volume (C), and proportion of patients with late gadolinium enhancement (E), with a reduction in LVEF (G). A similar pattern was seen when comparing these characteristics across tertiles of indexed extracellular volume (iECV) (B, D, F, and H). EDVi = indexed end-diastolic volume; LGE = late gadolinium enhancement; LV = left ventricle; LVEF = left ventricular ejection fraction.

Figure 4

Distribution of ECV% and Relationship With Clinical Events ECV% is normally distributed (A). When divided into tertiles, both the all-cause mortality rate (red squares) and cardiovascular mortality (purple squares) progressively increased across the tertiles. On Kaplan-Meier analysis, there was a progressive increase in all-cause mortality across tertiles of ECV% (B) (p = 0.009). ECV% remained an independent predictor of all-cause mortality on multivariable analysis (C) (hazard ratio: 1.10; p = 0.013). Abbreviations as in Figure 3.

Central Illustration

T1 Mapping Assessments of Myocardial Fibrosis in Aortic Stenosis Extracellular volume fraction (ECV%) using cardiovascular magnetic resonance (CMR) serves as an objective marker of left ventricular decompensation and is independently associated with long-term clinical outcomes in patients with aortic stenosis.