© Urban & Vogel 2003 Herz 744 Herz 28 · 2003 · Nr. 8 © Urban & Vogel Effects of ACE Inhibition versus Non-ACE Inhibitor Antihypertensive Treatment on Myocardial Fibrosis in Patients with Arterial Hypertension Retrospective Analysis of 120 Patients with Left Ventricular Endomyocardial Biopsies Christian G. Brilla, Heinz Rupp, Bernhard Maisch 1 Background and Purpose: In experimental arterial hyperten- sion, left ventricular hypertrophy (LVH) becomes pathologic with impaired myocardial function if myocardial fibrosis oc- curs. Myocardial fibrosis is associated with activated circulat- ing or local renin-angiotensin-aldosterone systems. The pri- mary objective of this retrospective study was to determine whether patients with arterial hypertension treated with an- giotensin-converting enzyme inhibitors (ACEI) have less my- ocardial fibrosis than patients on non-ACEI treatment. Material and Methods: We examined left ventricular (LV) en- domyocardial biopsies of 97 consecutive patients with hyper- tensive heart disease due to primary hypertension treated with either any ACEI for at least 6 months (n = 34; HTN + ACEI) or non-ACEI antihypertensive drugs (n = 63; HTN). Normal hearts designated for heart transplantation served as controls (n = 23; CTR). Myocyte diameter (MyoD) and collagen volume fraction (CVF) were measured by morphometry, and pro-ma- trix metalloproteinases (proMMPs) 2 and 9 by zymography. In a subset of 35 patients, LV myocardial stiffness was deter- Einfluss der ACE-Hemmung im Vergleich zu einer antihypertensiven Therapie ohne ACE-Hemmer auf die Myokardfibrose bei Patienten mit primärer arterieller Hypertonie. Eine retrospektive Analyse von 120 Patienten mit linksventrikulären Endomyokardbiopsien Hintergrund und Ziel: Bei experimenteller arterieller Hyperto- nie geht die Entwicklung einer Myokardfibrose mit aktivierten zirkulierenden oder lokalen Renin-Angiotensin-Aldosteron- Systemen einher. Dies führt zu einer pathologischen linksven- trikulären Hypertrophie (LVH) mit eingeschränkter Myokard- funktion. Sowohl tierexperimentell als auch in einer kleinen prospektiven klinischen Untersuchung an Patienten mit primärem Bluthochdruck konnte gezeigt werden, dass eine Behandlung mit einem Angiotensinkonversionsenzym-(ACE-) Hemmer zu einer Regression der Myokardfibrose führt, ein- Key Words: Hypertension · Left ventricular hypertrophy · Myocardial fibrosis · Matrix metalloproteinases · ACE inhibition Herz 2003;28:744–53 DOI 10.1007/s00059-003-2524-6 1 Division of Cardiology, Center of Internal Medicine, Philipps Univer- sity of Marburg, Germany. mined by left heart catheterization with calculation of stiff- ness constant k. Results: In HTN + ACEI or HTN, MyoD (21.8 ± 0.3 µm and 22.4 ± 0.3 µm, respectively) and CVF (5.3 ± 0.6% and 7.6 ± 0.7%, re- spectively) were increased (p < 0.01) compared with CTR (16.0 ± 0.4 µm and 0.5 ± 0.2%, respectively). In HTN + ACEI, CVF was significantly lower (p < 0.02) and proMMP 2 was higher (0.063 ± 0.013 OD/mg) compared with HTN (0.037 ± 0.006 OD/mg; p < 0.05) while no significant difference of MyoD was evident. We found no correlation between CVF and MyoD (r = 0.13; p = 0.47), a positive correlation between k and CVF (r = 0.71; p < 0.00001), and no correlation between k and MyoD (r = 0.22; p = 0.24). Conclusion: In patients with hypertensive heart disease, my- ocyte hypertrophy and myocardial fibrosis are present. My- ocardial fibrosis and not myocyte hypertrophy determines myocardial stiffness. ACEI appear to diminish myocardial fi- brosis associated with enhanced collagen degradation irre- spective of LVH regression.