Ventricular myocardial remodeling is a cause of heart failure in ARVD patients. Angiotensin-converting enzyme (ACE) inhibitors inhibit the TGF-B pathway and have an anti-apoptotic action. ACE inhibitors are currently prescribed to reduce hypertension, to treat heart failure or to protect the heart following ischemic insult. Expression patterns of matrix metalloproteinase-9 (MMP-9) and its specific inhibitors, tissue inhibitor of metalloproteinases (TIMP) 1 and 2, are closely correlated with physiological and pathological processes characterized by the degradation and accumulation of the extracellular matrix. We aimed to study the turnover of tissue collagen in patients.

Dosages ofmmP9 and its inhibitors, TIMP1 and TIMP2, were performed in 26 patients treated with beta blockers (BB) and ACEs and in 20 patients treated with BB without ACEs. Each patient had blood samples taken one year apart. Tissue collagen turnover was identified by the evolution of themmP9/TIMP1 ratio and themmP9/TIMP2 ratio between the 2 time samples (Student’s t-test for paired samples).

A stabilization of themmP9/TIMP1 andmmP9/TIMP2 ratio was present in patients treated with angiotensin-converting enzyme inhibitors (3.04±1.88 vs 3.36±2.86 formmP9/TIMP1; 8.79±8.18 vs 8.31±6.70 formmP9/ TIMP2). In contrast, there was a significant increase of themmP9/TIMP1 ratio in patients treated without ACE inhibitors (2.74±2.36 vs 4.53±3.62, p=0.03). No significant increase ofmmP9/TIMP2 was observed (7.39±5.17 vs 9.00±6.64) in these patients. The increasedmmP9/TIMP1 ratio for BB patients was triggered by an increase inmmP9 concentration (554.8±368.5 vs. 876.0±619.7, p=0.04) and a decrease in TIMP1 concentration (223.2±72.8 vs 205.1±71.6, p=0.01).

This study suggests that ACE inhibitors decrease myocardial damage in ARVD patients and strengthens the need for a prospective clinical evaluation of antifibrotic drugs in this disease.