Reappraising myocardial fibrosis in severe aortic stenosis: an invasive and non-invasive study in 133 patients

Figures

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  Figure 1. Aortic stenosis, myocardial hypertrophy and fibrosis by imaging and biopsy. Four exemplar patients showing continuous-wave Doppler (maximum velocities >4m/s; Column 1), short axis cine stills demonstrating degrees of left ventricular hypertrophy (Cine; Column 2), matching late gadolinium enhancement images (LGE, Column 3), matching extracellular volume fraction (ECV, Column 4), myocardial biopsy stained with picrosirus red [collagen volume fraction (CVF), Column 5]. Patient A has minimal LVH, no LGE, an ECV of 28.4% and minimal biopsy subendocardial fibrosis (CVF 4.6%). Patient B has concentric LVH, patchy non-infarct LGE, an ECV of 29.9% and moderate biopsy fibrosis (CVF 19.3%). Patient C has concentric LVH, widespread non-infarct LGE, an ECV of 36.5%, and severe biopsy fibrosis (CVF 24.5%). Patient D has mild concentric LVH, subtle subendocardial LGE (white arrow), an ECV of 24.5%, thickened endocardium, and subendocardial scarring. Scale bars (Columns 2–4) equal 5 cm.

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  Figure 2. Biopsies with and without endocardium—presence of a gradient of fibrosis. (A) Collagen volume fraction in biopsies with and without endocardium. (B) Collagen volume fraction in samples with endocardium divided in tertiles. Box plots show the 5th and 95th (vertical lines), 25th and 75th (boxes), and 50th (horizontal line) percentile values for collagen volume fraction. (C) Representative images of three biopsies with endocardium (left panel needle and middle and right panel scalpel). (D) Representative images of four biopsies without endocardium (needle).

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  Figure 3. Patterns of fibrosis—endocardial thickening and myocardial microscars and interstitial fibrosis. (A) The endocardium in a control subject (left panel) and in two aortic stenosis patients at the same magnification. The arrows show the endocardial thickness (green in normal, black in aortic stenosis). (B) Higher magnification showing minimal subendocardial interstitial fibrosis in a control subject (left panel) and extensive microscars and interstitial fibrosis in two aortic stenosis patients. Circles identify microscars and arrows diffuse fibrosis.

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  Figure 4. Association of late gadolinium enhancement with collagen volume fraction. Late gadolinium enhancement (LGE) quantified in grams by a three standard deviation method correlated strongest with collagen volume fraction (CVF) in endocardial containing samples (linear fit: y = 0.814x + 3.109).

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  Figure 5. Associations of imaging and blood biomarkers. Late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) correlated with NT-proBNP (A and B) and with hs-TnT ( C and D) (linear fit: A y = 0.119x – 1.498; B y = 0.037x + 0.103; C y = 0.025x + 1.567; Dy = 0.110x + 1.008).