Activation delay after premature stimulation in chronically diseased human myocardium relates to the architecture of interstitial fibrosis.
BACKGROUND
Progressive activation delay starting at long coupling intervals of premature stimuli has been shown to correlate with sudden cardiac death in patients with hypertrophic cardiomyopathy. The purpose of this study was to elucidate the mechanism of increased activation delay in chronically diseased myocardium.


RESULTS
High-resolution unipolar mapping (105, 208, or 247 recording sites with interelectrode distances of 0.8, 0.5, or 0.3 mm, respectively) of epicardial electrical activity was carried out during premature stimulation in 11 explanted human hearts. The hearts came from patients who underwent heart transplantation and were in the end stage of heart failure (coronary artery disease, 4; hypertrophic cardiomyopathy, 1; and dilated cardiomyopathy, 6). Eight hearts were Langendorff-perfused. Epicardial sheets were taken from the remaining hearts and studied in a tissue bath. Activation maps and conduction curves were constructed and correlated with histology. Conduction curves revealing prominent increase of activation delay were associated with zones of dense, patchy fibrosis with long fibrotic strands. Dense, diffuse fibrosis with short fibrotic strands only marginally affected conduction curves. The course of conduction curves in patchy fibrotic areas greatly depended on the direction of propagation relative to fiber direction.


CONCLUSIONS
The study demonstrates that in chronically diseased human myocardium, nonuniform anisotropic characteristics imposed by long fibrotic strands cause a progressive increase of activation delay, starting at long coupling intervals of premature stimuli. The increase strongly depends on the direction of the wave front with respect to fiber direction and the architecture of fibrosis.
Kawara
T
T
Experimental and Molecular Cardiology Group, Cardiovascular Research Institute, Amsterdam, the Netherlands.
Derksen
R
R
de Groot
J R
JR
Coronel
R
R
Tasseron
S
S
Linnenbank
A C
AC
Hauer
R N
RN
Kirkels
H
H
Janse
M J
MJ
de Bakker
J M
JM
D000328:Adult; D002908:Chronic Disease; D004558:Electric Stimulation; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D010477:Perfusion; D013997:Time Factors