Global remodeling of the ventricular interstitium in idiopathic myocardial fibrosis and sudden cardiac death.
OBJECTIVE
Characterization of a distinct, and as yet unexplained phenotype of sudden cardiac death (SCD).


BACKGROUND
In a subgroup of patients with SCD, postmortem findings are limited to isolated idiopathic myocardial fibrosis (IMF). The absence of confounding factors may facilitate evaluation of the relationship between myocardial fibrosis and ventricular arrhythmogenesis.


METHODS
Six patients with IMF were identified from a postmortem, consecutive 13-year series of 270 subjects presenting with SCD. Ventricular interstitial remodeling was assessed quantitatively and qualitatively and comparisons made with 6 age- and sex-matched control subjects who suffered noncardiac death. Myocardial collagen volume fraction and perivascular fibrosis ratio were determined and evidence for inflammatory response and apoptotic cell death was sought. The potential role of transforming growth factor beta 1 (TGF-beta(1)) in the pathogenesis of IMF was evaluated.


RESULTS
Overall myocardial collagen volume fraction was 1.6-fold higher in IMF (mean age 34 +/- 4 yrs) vs. controls (mean age 34 +/- 4 yrs, .022 +/- .001 vs .013 +/- .001; P < .001). Collagen volume fraction increase was diffuse but disproportionately so in the LV inferior wall (3.4-fold increase; .035 +/- .005 vs .012 +/- .018; P < .001). Perivascular fibrosis ratio was also increased (.770 +/- .014 vs .723 +/- .010; P = .007). There was no evidence of either myocardial inflammatory response or myocyte apoptosis in cases or controls. Expression of TGF-beta(1) was significantly increased in IMF vs controls.


CONCLUSIONS
IMF involves diffuse and heterogeneous remodeling of the ventricular interstitium, with a predilection for the LV inferior wall. TGF-beta(1) is a potential mediator of interstitial remodeling in IMF and SCD.
John
Benjamin T
BT
Division of Cardiology, Oregon Health & Science University, Portland, Oregon, USA.
Tamarappoo
Balaji K
BK
Titus
Jack L
JL
Edwards
William D
WD
Shen
Win-K
WK
Chugh
Sumeet S
SS
D000328:Adult; D000704:Analysis of Variance; D017209:Apoptosis / Q000502:physiology; D002102:Cadaver; D016022:Case-Control Studies; D003094:Collagen / Q000378:metabolism; D016757:Death, Sudden, Cardiac; D004719:Endomyocardial Fibrosis / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D020257:Ventricular Remodeling / Q000502:physiology*
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen