Short-term Effect of ACE Inhibition in Severe Aortic Stenosis
Short-term Effect of ACE Inhibition in Severe Aortic Stenosis
Background In patients with severe aortic stenosis (AS), treatment with angiotensin-converting enzyme inhibitors has previously been considered contraindicated. However, there is a lack of clinical evidence to confirm these potential hemodynamic risks and benefits.
Methods Forty-four patients with severe AS (aortic valve area <1 cm) were randomized to treatment with trandolapril 22 mg daily/placebo (1:1). Right heart catheterization and echocardiography were performed at rest and during exercise at baseline and on day 3. Follow-up was performed before valve replacement or after a maximum of 8 weeks, when exercise echocardiography was repeated.
Results Compared with placebo, systolic blood pressure and systemic arterial compliance significantly changed at day 3 (−14 ± 11 vs −5 ± 13 mm Hg, P = .02, and 0.08 ± 0.16 vs −0.05 ± 0.86 mL/m per mm Hg, P = .03, respectively). Changes in left ventricular end systolic volume (LVESV) was nonsignificant (−8 ± 9 vs −3 ± 11 mL, P = .17). At a median of 49 days of follow-up, changes in LVESV and N-terminal pro-brain natriuretic peptide were even lower revealing significant differences between the groups (−7.8 ± 2.6 vs −0.5 ± 2.5 mL, P = .04, and −19 ± 7 vs 0.8 ± 6 pmol/L, P = .04, respectively). No episodes of symptomatic hypotension were noted, and other hemodynamic parameters remained unchanged.
Conclusion Angiotensin-converting enzyme inhibition in severe AS caused a decrease in LVESV and N-terminal pro-brain natriuretic peptide with other hemodynamic parameters preserved both at rest and during exercise implying hemodynamic improvement with left ventricular unloading.
Aortic stenosis (AS) due to calcification of the aortic valve is a common disease, affecting 2% to 9% of the elderly. With increasing life expectancy, the prevalence of AS is expected to rise in the future. Hitherto, no disease-modifying drug has been identified, and the only effective treatment available is aortic valve replacement. Along with progression of the valve stenosis, structural changes of the left ventricle (LV) may occur that allow adaptation to the increase in afterload. This includes development of hypertrophy and eventually fibrosis of LV and the subsequent impairment of systolic and diastolic function. Angiotensin-converting enzyme inhibitors (ACE-Is) might reduce these changes by inhibiting the renin-angiotensin system, and potential benefits to the aortic valve and the LV have been suggested. However, there are some concerns about its use. In severe AS, treatment with ACE-I has been considered contraindicated, due to the theoretical possibility that arterial vasodilatation in combination with fixed valve obstruction might result in an increase in the transaortic gradient, resulting in hypotension and thereby myocardial hypoperfusion and a subsequent decrease in cardiac output, especially during exercise. To date, however, there has been no clinical evidence to confirm these potential risks or benefits with respect to hemodynamic characteristics. We performed a prospective double-blinded study investigating the safety and acute hemodynamic effects of ACE-I treatment in patients with severe symptomatic and asymptomatic AS.
Abstract and Introduction
Abstract
Background In patients with severe aortic stenosis (AS), treatment with angiotensin-converting enzyme inhibitors has previously been considered contraindicated. However, there is a lack of clinical evidence to confirm these potential hemodynamic risks and benefits.
Methods Forty-four patients with severe AS (aortic valve area <1 cm) were randomized to treatment with trandolapril 22 mg daily/placebo (1:1). Right heart catheterization and echocardiography were performed at rest and during exercise at baseline and on day 3. Follow-up was performed before valve replacement or after a maximum of 8 weeks, when exercise echocardiography was repeated.
Results Compared with placebo, systolic blood pressure and systemic arterial compliance significantly changed at day 3 (−14 ± 11 vs −5 ± 13 mm Hg, P = .02, and 0.08 ± 0.16 vs −0.05 ± 0.86 mL/m per mm Hg, P = .03, respectively). Changes in left ventricular end systolic volume (LVESV) was nonsignificant (−8 ± 9 vs −3 ± 11 mL, P = .17). At a median of 49 days of follow-up, changes in LVESV and N-terminal pro-brain natriuretic peptide were even lower revealing significant differences between the groups (−7.8 ± 2.6 vs −0.5 ± 2.5 mL, P = .04, and −19 ± 7 vs 0.8 ± 6 pmol/L, P = .04, respectively). No episodes of symptomatic hypotension were noted, and other hemodynamic parameters remained unchanged.
Conclusion Angiotensin-converting enzyme inhibition in severe AS caused a decrease in LVESV and N-terminal pro-brain natriuretic peptide with other hemodynamic parameters preserved both at rest and during exercise implying hemodynamic improvement with left ventricular unloading.
Introduction
Aortic stenosis (AS) due to calcification of the aortic valve is a common disease, affecting 2% to 9% of the elderly. With increasing life expectancy, the prevalence of AS is expected to rise in the future. Hitherto, no disease-modifying drug has been identified, and the only effective treatment available is aortic valve replacement. Along with progression of the valve stenosis, structural changes of the left ventricle (LV) may occur that allow adaptation to the increase in afterload. This includes development of hypertrophy and eventually fibrosis of LV and the subsequent impairment of systolic and diastolic function. Angiotensin-converting enzyme inhibitors (ACE-Is) might reduce these changes by inhibiting the renin-angiotensin system, and potential benefits to the aortic valve and the LV have been suggested. However, there are some concerns about its use. In severe AS, treatment with ACE-I has been considered contraindicated, due to the theoretical possibility that arterial vasodilatation in combination with fixed valve obstruction might result in an increase in the transaortic gradient, resulting in hypotension and thereby myocardial hypoperfusion and a subsequent decrease in cardiac output, especially during exercise. To date, however, there has been no clinical evidence to confirm these potential risks or benefits with respect to hemodynamic characteristics. We performed a prospective double-blinded study investigating the safety and acute hemodynamic effects of ACE-I treatment in patients with severe symptomatic and asymptomatic AS.
