Increased myocardial collagen turnover in patients with progressive cardiac conduction disease.

BACKGROUND: Histopathologically, progressive cardiac conduction disease (PCCD) is characterized by progressive fibrosis and sclerodegenerative changes in the proximal and distal conduction system of the heart. Therefore, we sought to determine the serum levels of myocardial collagen turnover markers, extracellular matrix components, transforming growth factor beta(1) (TGFbeta(1)), and bone morphogenic protein-7 (BMP-7) in this population. METHODS: Study population included 20 patients (6 M/14 F, mean age 76 +/- 8 years) with acquired, permanent 2:1, or complete atrioventricular block and compared with age- and sex-matched, asymptomatic, healthy control subjects (n = 18, 6 M/12 F, mean age 75 +/- 7 years). Serum myocardial collagen turnover markers:matrix metalloproteinases (MMP-1, 2, 9), tissue inhibitor of matrix metalloproteinase (TIMP-1), amino-terminal propeptide of procollagen type I (PINP) and type III (PIIINP), carboxy-terminal telopeptide of collagen type I (CITP), and carboxy-terminal propeptide of procollagen type I (PICP), serum extracellular matrix components (laminin and fibronectin), TGFbeta(1), and BMP-7 levels were measured in both groups. RESULTS: Serum PICP (849 +/- 396 vs 631 +/- 294 ng/mL, P = 0.04), PIIINP (3.7 +/- 1.3 vs 3 +/- 1 mug/L, P = 0.03), CITP (0.68 +/- 0.35 vs 0.48 +/- 0.25 ng/mL, P = 0.037), and plasma MMP-9 (58.8 +/- 56 vs 25.9 +/- 17.3 ng/mL, P = 0.006) levels were higher in patient population compared to control subjects. Serum MMP-1 (24.1 +/- 20.5 vs 13.6 +/- 7.5 ng/mL, P = 0.045) and MMP-2 (1310 +/- 139 vs 1186 +/- 163 ng/mL, P = 0.01) levels were higher in control subjects compared to patient population. There was no difference in serum TIMP-1, PINP, laminin, fibronectin, TGFbeta(1), and BMP-7 levels between two groups. CONCLUSION: Our findings demonstrate the presence of increased myocardial collagen turnover and active fibrotic process in patients with PCCD compared to control subjects.

Demonstration of ventricular myocardial extensions into the pulmonary artery and aorta beyond the ventriculo-arterial junction.

BACKGROUND: A subgroup of outflow tract (OT) ventricular tachycardias (VT) originate from the aortic sinuses or the main stem of the pulmonary artery. The anatomic substrate for these tachycardias is unknown. The aim of this study was to investigate the presence of ventricular myocardial extensions (VME) into the pulmonary artery (PA) and aorta (Ao) beyond the ventriculo-arterial junction (VAJ) and determine the anatomical and histological characteristics of these muscle extensions. METHODS: Ninety-five consecutive human hearts obtained at autopsy were studied. Longitudinal strips of tissue containing each cusp, aortic, and pulmonary artery walls and left and right ventricular outflow tracts were excised and histologically analyzed. Anatomical measurements, including length and thickness of VMEs, obtained at autopsy, were made. RESULTS: VMEs beyond the VAJ were found in 21 of 95 (22%) patients studied. VMEs were found in 16 of 95 PAs (17%) and 7 of 95 Aos (7%) were examined. VMEs were located within the adventitia in 23 (88%) and on the epicardial surface in three (12%). The majority of VMEs were in continuity with the underlying ventricular OT muscle tissue. Myocellular hypertrophy and fibrosis were present in 19 (73%) and fatty tissue between the layers of VME in 18 (69%). Clinical data were available in 14 of 21 patients with positive VME. None of the patients (clinical data available group) had history of cardiac disease or signs or symptoms (palpitations or syncope) of cardiac disease. CONCLUSIONS: VMEs into the PA and Ao beyond the VAJ are relatively common. It seems that their mere presence does not predispose to OT VTs. There are probably intrinsic arrhythmogenic properties in tissues specific to these regions in those patients who develop OT VTs.