Measurement of myocardial extracellular volume fraction and cardiomyocyte diameter before and 6 months after aortic valve replacement in patients with severe aortic stenosis

Presenting Author(s)

• 

  Noor Sharrack, MD, PhD

  Cardiology registrar
  Leeds institute of cardiovascular and metabolic medicine
  Leeds, England, United Kingdom

Primary Author(s)

• 

  Noor Sharrack, MD, PhD

  Cardiology registrar
  Leeds institute of cardiovascular and metabolic medicine
  Leeds, England, United Kingdom

Co-Author(s)

• AM

  Alex Makins

  Research Fellow
  University of Leeds
  Leeds, United Kingdom
• JB

  John D D. Biglands, PhD, MSc

  Clinician scientist
  Leeds Institute of Cardiovascular and Metabolic Medicine
  Leeds, England, United Kingdom
• PK

  Peter Kellman, PhD

  Director
  National Heart, Lung, and Blood Institute, National Institutes of Health, United States
• 

  Sven Plein, MD, PhD

  Professor of Cardiology
  Leeds Institute of Cardiovascular and Metabolic Medicine
  Leeds, England, United Kingdom
• DB

  David L. Buckley, PhD

  Professor of Medical Physics
  Leeds Institute of Cardiovascular and Metabolic Medicine, United Kingdom

Background: Extra cellular volume fraction (ECV) is an independent predictor of mortality in aortic stenosis (AS). ECV can be measured using myocardial T1 maps acquired before and after contrast administration. Standard ECV measurements do not consider the limited rate of water exchange (WX) between cardiomyocytes and the extracellular matrix which can result in underestimated ECV at higher contrast agent concentrations.

The objective was to estimate ECV in patients with severe AS before and after surgical aortic valve replacement (AVR) using a 2-site exchange model (2SXM) that also enables estimates of cell water residence time (τ_ic; an indicator of the minor diameter of the cardiomyocytes).

Methods: 20 patients (67 ± 6 years) with severe AS, referred for AVR, underwent MRI on a 3T MR system before and 6 months after AVR. T1 measurements were made using a multiparametric saturation-recovery single-shot acquisition before and at multiple time points post-injection of contrast agent. A 2SXM and standard linear model (LM) were used to estimate ECV from which indexed cell and matrix volumes were calculated. The 2SXM model was also used to estimate τ_ic.

Results: Data were acquired before and 174 (157 to 267) days after AVR. Indexed left ventricular mass reduced following AVR, from 80 ± 18 g/m² to 63 ± 12 g/m² (p< 0.001). ECV estimates increased from 22 ± 4% to 29 ± 5% (p< 0.001) using the LM compared to 28 ± 5% to 33 ± 5% (p=0.010) using the 2SXM. Indexed cell volume decreased from 59 ± 14 cm³/m² to 43 ± 10 cm³/m² (p < 0.001; LM) and from 55 ± 14 cm³/m² to 41 ± 9 cm³/m² (p< 0.001; 2SXM). Indexed matrix volume did not change significantly by either method (LM, 17 ± 4 cm³/m² to 17 ± 3 cm³/m²; 2SXM, 21 ± 5 cm³/m² to 19 ± 4 cm³/m²). τ_ic decreased from 0.21 ± 0.12 s to 0.12 ± 0.09 s (p=0.006).

Conclusion: Cellular hypertrophy regressed 6 months following AVR; the extracellular matrix volume did not change significantly. τ_ic decreased post AVR indicating that the reduction in cell volume can be largely attributed to a reduction in cardiomyocyte diameter.

Table 1: Basic demographic and CMR parameters pre and post AVR. Results presented as mean ±SD or median (range). P values considered significant at <0.05 highlighted with *. AVR- aortic valve replacement, LVEF- left ventricular ejection fraction, LVEDV- left ventricular end diastolic volume, LVEDV(i)- left ventricular end diastolic volume (indexed), MWT- maximal wall thickness, LVM- left ventricular mass, LVMi- left ventricular mass indexed

Characteristic	Patients pre AVR (n=20)	Patients 6 months post AVR (n=20)	P value
Haematocrit (%)	42 ± 5	39 ± 6	0.005*
LVEF (%)	60 ± 8	61 ± 7	0.723
LVEDV (ml)	145 ± 52	132 (69 to 239)	0.070
LVEDV(i) (ml/m2)	73 ± 19	66 (49 to 105)	0.114
MWT (mm)	14 ± 2	11 ± 2	< 0.001*
LVM (g)	158 ± 53	126 ± 36	< 0.001*
LVMi (g/m2)	80 ± 18	63 ± 12	< 0.001*

Figure 1 Change in ECV following AVR measured using the 2SXM (blue) and the LM (red). The LM slightly overestimates the increase in ECV compared to the 2SXM (p = 0.034).
Change in indexed cell and matrix volumes following AVR measured using the 2SXM (blue & green) and the LM (red & orange). Both models show a significant reduction in cell volume (p < 0.001) and no significant change in matrix volume, but the LM overestimates the cell volume regression compared to the 2SXM (p = 0.003).