Morphology and significance of the left ventricular collagen network in young patients with hypertrophic cardiomyopathy and sudden cardiac death

BACKGROUND Hypertrophic cardiomyopathy (HCM) is a primary cardiac disease w ith a diverse clinical spectrum, in which many of the abnormal structural a nd pathophysiologic features are consequences of inappropriate left ventric ular hypertrophy. METHODS We analyzed the amount, distribution and structure of the cardiac c ollagen network in transmural sections of the ventricular septum (thickness 17 to 40 mm, mean 25 mm) in 16 previously asymptomatic children and young adults with HCM (11 to 31 years of age, mean 20 years) who died suddenly. T he morphologic appearance and volume fractions of interstitial (matrix) and perivascular (adventitial) collagen were analyzed with polarization micros copy and computerized videodensitometry in picrosirius red-stained sections . Findings were compared with 16 structurally normal hearts, 5 with systemi c hypertension and 6 infants who died of HCM. RESULTS Adults and young children with HCM had an eightfold greater amount of matrix collagen compared with normal controls (14.1 +/- 8.8% vs. 1.8 +/- 1% of the tissue section; p < 0.0001), and a threefold increase compared w ith patients with systemic hypertension (4.5 +/- 1.3%; p < 0.001) and infan ts with HCM (4.0 +/- 2.4%; p < 0.001). Compared with normal controls and hy pertensives, adults and young children (and infants) with HCM showed increa sed numbers and thickness of each collagen fiber component of the matrix (p erimysial coils, pericellular weaves and struts), which were often arranged in disorganized patterns. In HCM patients, the amount of collagen was not a consequence of other clinical, demographic and morphologic disease variab les. CONCLUSIONS Left ventricular collagen matrix in young, previously asymptoma tic patients with HCM who died suddenly is morphologically abnormal and sub stantially increased in size. The enlarged matrix collagen compartment is p resent in HCM at an early age, further expands during growth, is partially responsible for increased ventricular septal thickness and likely represent s a primary morphologic abnormality in this disease. These findings support the view that the complex HCM disease process is not confined to sarcomere protein abnormalities, bur also involves connective tissue elements. (C) 1 999 by the American College of Cardiology.