Hemodynamic effects of a single oral dose of enalapril among children with asymptomatic chronic mitral regurgitation.
BACKGROUND
Angiotensin-converting enzyme inhibitors have been shown to have beneficial effects in the short- and long-term treatment of adult patients with chronic mitral regurgitation. The safety and efficacy of such treatment have not been established for children. The objective of this study was to assess the effect of the angiotensin-converting enzyme inhibitor enalapril on the severity of valvar mitral regurgitation and the systolic performance of overloaded left ventricle of children.


METHODS
Ten patients 3 to 16 years of age (mean age 9.6 +/- 3.8 years) with moderate to severe chronic mitral insufficiency were examined by means of Doppler echocardiography before and 2 hours after receiving a single oral dose of enalapril (0.40 mg/kg). Effective regurgitant orifice area, regurgitant volume and fraction, left ventricular end-diastolic and end-systolic volumes indexed for body surface area, left ventricular pump function (total ejection fraction), left ventricular contractility (stress-adjusted velocity of shortening) and afterload (peak systolic and end-systolic circumferential wall stress), and systemic vascular resistance were calculated before and after treatment.


RESULTS
The following values decreased significantly compared with baseline values: effective regurgitant orifice area (36.2 +/- 17.4 versus 25.9 +/- 16.5 mm(2), P =.00008), regurgitant volume (53.6 +/- 27.4 versus 36.1 +/- 24.5 mL, P =.0002), regurgitant fraction (56.7 +/- 14.5% versus 39.9 +/- 17.0%, P =. 0009), left ventricular end-diastolic volume indexed for body surface area (81.3 +/- 17.4 versus 76.1 +/- 16.1 mL/m(2), P =.005), left ventricular end-systolic volume indexed for body surface area (26.7 +/- 9.1 versus 22.6 +/- 8.9 mL/m(2), P =.02), afterload (peak systolic circumferential wall stress 135.8 +/- 15.3 versus 123.5 +/- 19.7 g/cm(2), P =.005; end-systolic circumferential wall stress 57.8 +/- 12.4 versus 48.3 +/- 12.8 g/cm(2), P =.005), and systemic vascular resistance (2012.2 +/- 536.1 versus 1622.7 +/- 389 dyne. sec. cm(-5), P =.005). Left ventricular pump function increased (total ejection fraction 67.6 +/- 5.7% versus 71.7 +/- 6.5%, P =. 005) without significant changes in left ventricular contractility (stress-adjusted velocity of shortening -0.35 +/- 0.8 versus -0.21 +/- 1.3 SD, P not significant).


CONCLUSIONS
The data showed that for pediatric patients single-dose treatment with oral enalapril reduces the severity of mitral regurgitation and improves left ventricular loading conditions and systolic performance without impairment of myocardial contractility. Persistence of these unloading effects in long-term therapy might slow the evolution of left ventricular dysfunction caused by overload-induced myocardial damage and possibly delay the time at which surgical repair or replacement of the mitral valve becomes necessary.
Calabrò
R
R
Department of Pediatric Cardiology, II University of Naples, Italy.
Pisacane
C
C
Pacileo
G
G
Russo
M G
MG
D000284:Administration, Oral; D000293:Adolescent; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001783:Blood Flow Velocity / Q000187:drug effects; D002306:Cardiac Volume / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015150:Echocardiography, Doppler; D004656:Enalapril / Q000008:administration & dosage*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008944:Mitral Valve Insufficiency / Q000000981:diagnostic imaging / Q000188:drug therapy*; D009200:Myocardial Contraction / Q000187:drug effects; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril