Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis

Figures

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  Central Illustration. Extracellular Volume Fraction Dichotomizes the Myocardium Into Cell and Matrix Compartments (A) The in vivo myocardium consists of cells and the surrounding extracellular matrix. Reactive fibrosis is characterized by expansion of the extracellular matrix, whereas replacement fibrosis follows cell death by focal scar. (B) Cardiovascular magnetic resonance measures both focal fibrosis (scar) by late gadolinium enhancement imaging, where the scar appears bright, and diffuse fibrosis by extracellular volume fraction (ECV) imaging. The ECV divides the myocardium into cell and matrix compartments and allows calculation of cell and matrix volumes. (C) A patient with a left ventricular (LV) volume of 100 ml and an ECV of 25% would have a cell volume of 75 ml and a matrix volume of 25 ml. Regression of left ventricular mass following aortic valve replacement can be driven by matrix regression alone, where the ECV reduces; by cellular regression alone, where the ECV increases; or by a proportional regression in cellular and matrix compartments, where the ECV is unchanged.

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  Figure 1. Study Flow Chart A total of 181 patients with severe, symptomatic aortic stenosis were recruited (48% of all surgical aortic valve replacements [AVR] at our institution [University College London Hospital NHS Trust, London, United Kingdom]). Before AVR, 10 patients were excluded (claustrophobia [n = 4], cardiac amyloid [n = 2], severe mitral regurgitation [n = 2], pseudosevere aortic stenosis [n = 1], Fabry disease [n = 1]), and 3 patients did not undergo AVR and were treated medically. Following AVR (164 surgical, 4 transcatheter), 4 further patients were excluded because of cardiac amyloid. By 1 year, there were 11 deaths and 16 patients with pacemakers; 21 patients declined follow-up. A total of 116 patients underwent 1-year follow-up assessment. CABG = coronary artery bypass grafting; CMR = cardiac magnetic resonance; eGFR = estimated glomerular filtration rate; mAVR = mechanical aortic valve replacement; pre OP = pre-operative; TAVR = transcatheter aortic valve replacement; tAVR = tissue bioprosthetic aortic valve replacement.

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  Figure 2. Cell and Matrix Remodeling 1 Year After AVR (A) At 1-year post–aortic valve replacement (AVR), there was a 19% reduction in indexed left ventricular (LV) mass (88 ± 26 g/m2 to 71 ± 19 g/m2; p < 0.001) (B) The extracellular volume fraction (ECV) increased unexpectedly from 28.2 ± 2.9% to 29.9 ± 4.0% (p < 0.001). (C) Derived indexed cell volume (left ventricular mass index × [1 − ECV]) reduced by 22% (64 ± 18 ml/m2 to 50 ± 13 ml/m2; p < 0.001), and (D) derived indexed matrix volume (left ventricular mass index × ECV) reduced by 16% (25 ± 9 ml/m2 to 21 ± 7 ml/m2; p < 0.001).

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  Figure 3. Reverse Myocardial Remodeling After AVR A 66-year-old man with severe aortic stenosis (peak velocity 4.66 m/s; mean gradient 57 mm Hg; aortic valve area 0.5 cm2). Cardiac magnetic resonance before aortic valve replacement (AVR) showed concentric left ventricular (LV) hypertrophy (133 g/m2). Late gadolinium enhancement (LGE) demonstrated limited nonischemic focal scar (5.3 g/m2 [4%]). Extracellular volume fraction (ECV) was 27.5%. At 1 year after AVR (mechanical bileaflet valve), there was a 22% reduction in LV mass (to 104 g/m2). The LV mass regression resulted from a 24% reduction in cell volume and a 17% reduction in matrix volume, so the ECV rose to 29.1%. The focal fibrosis (late gadolinium enhancement [LGE]) was unchanged (5.4 g/m2 [5%]), but it slightly increased when it was expressed as a percentage of the LV mass.