Intramyocardial adiposity after myocardial infarction: new implications of a substrate for ventricular tachycardia

Circulation. 2013 Nov 19;128(21):2296-308. doi: 10.1161/CIRCULATIONAHA.113.002238. Epub 2013 Sep 13.

Abstract

Background: Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI.

Methods and results: Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI-; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT-; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular 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 (r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (P>0.29). However, the MI+VT+ group demonstrated a significant (all P≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT- group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 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 left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.

Keywords: adipose tissue; cicatrix; connexin 43; electrophysiology; myocardial infarction; scar; tachycardia, ventricular.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity*
  • Animals
  • Collagen / metabolism
  • Connexin 43 / metabolism
  • Disease Models, Animal
  • Electrophysiologic Techniques, Cardiac
  • Gap Junctions / metabolism
  • Gap Junctions / pathology
  • Heart Conduction System / metabolism
  • Heart Conduction System / pathology
  • Male
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / physiopathology
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Orchiectomy
  • Sheep
  • Tachycardia, Ventricular / metabolism
  • Tachycardia, Ventricular / pathology*
  • Tachycardia, Ventricular / physiopathology
  • Ventricular Remodeling / physiology

Substances

  • Connexin 43
  • Collagen