Short-term hemodynamic effect of angiotensin-converting enzyme inhibition in patients with severe aortic stenosis: a placebo-controlled, randomized study.
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(2)) 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(2) 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.


CONCLUSIONS
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.
Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: md@dadlnet.dk.
Morten
M
Dalsgaard
Department of Cardiology, Copenhagen University Hospital, Hillerød Hospital, Hillerød, Denmark.
Kasper
K
Iversen
Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Jesper
J
Kjaergaard
Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Peer
P
Grande
Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Jens Peter
JP
Goetze
Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Peter
P
Clemmensen
Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
Christian
C
Hassager
D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001024:Aortic Valve Stenosis / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril