Intramyocardial Adiposity Post-Myocardial Infarction: New Implications of a Substrate for Ventricular Tachycardia
Background—Collagen has been attributed as the principle structural substrate of ventricular tachycardia (VT) post-myocardial infarction (MI) even though adiposity of myocardium post-MI is well recognised histologically. We investigated the association of intramyocardial adiposity in comparison to collagen on electrophysiological (EP) properties, connexin-43 (Cx43) expression, and VT induction post-MI.
Methods and Results—Simultaneous, left ventricular (LV) plunge-needle, and noncontact mapping was performed in sheep (a) without MI (MI-, n=5), (b) with MI and inducible VT (MI+VT+, n=7) and (c) with MI and no inducible VT (MI+VT-, n=8). Histological intramyocardial quantity of adipose, collagen, and degree of discontinuity was co-registered with EP parameters (MI+, 290 specimens). Additional assessment of Cx43 expression was performed. LV scar contained a body-mass-independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density, and discontinuity contributed to a greater inverse correlation (r) with conduction velocity (CV, r: adipose=0.39, discontinuity=0.45, collagen=0.26), and electrogram amplitude (Vpp, r: adipose=0.73, contiguity=0.77, collagen=0.68), compared to collagen. Collagen density was similar between MI+ groups (p>0.29). However the MI+VT+ group demonstrated a significant (all p<=0.01) increase of adipose (8%) and discontinuity (qualitative); and decrease of CV (13%), and Vpp (21%) at MI borders compared to the MI+VT- group. In scar, myocytes adjacent to fibro-fatty interfaces demonstrated increased Cx43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation, and exhibited attenuation of excitation wavelength (p<0.001).
Conclusions—Intramyocardial adiposity, in association with myocardial discontinuity within LV scar borders is a significant factor associated with altered EP properties, aberrant Cx43 expression, and increased propensity for VT post-MI.
- connexin43 expression
- cardiac gap junction connexins
- adipose tissue
- myocardial infarction
- ventricular tachycardia
- conduction velocity
- Received February 26, 2013.
- Revision received August 23, 2013.
- Accepted August 27, 2013.