Hypertrophic cardiomyopathy in pediatric patients: effect of verapamil on regional and global left ventricular diastolic function.
OBJECTIVE
To assess the effects of treatment with verapamil on regional and global left ventricular (LV) diastolic function in paediatric patients with hypertrophic cardiomyopathy (HCM).


METHODS
Twelve patients (age range 5.1 to 12.3 years, median 8.6) with HCM were evaluated during ongoing chronic oral treatment with verapamil (4 mg/kg/day) and four days after withdrawal of therapy. Twelve age- and body surface area-matched normal children served as controls. In an echocardiographic study, global LV diastolic function was evaluated by assessing isovolumic relaxation time (IVRT) and mitral flow indexes, including peak filling rate normalized to mitral stroke volume (PFR/SV). In addition, regional LV diastolic function was assessed by pulsed-wave Doppler tissue imaging at the subendocardial portion of the middle region of the anterior and posterior interventricular septum, and anterolateral and inferior walls to measure the peak velocities and the velocity-time integrals of myocardial excursion in both early diastole and atrial systole. In addition, as an index of diastolic asynchrony (AsyI), the variation in time to peak filling rate, measured as the time from the peak of the R wave on the electrocardiogram to the peak of the regional E wave, among the four myocardial regions was defined by subtracting the smallest value from the greatest and expressing the difference as a percentage of the smallest value.


RESULTS
Compared with the controls, patients with HCM without therapy showed a longer IVRT (P<0.01) and a decrease in PFR/SV (P<0.01) without a compensatory increase in filling during atrial systole. Oral administration of verapamil induced a significant shortening of the IVRT (P=0.003) and an increase in PFR/SV (P=0.02). Furthermore, patients with HCM without therapy showed a significantly longer time to peak filling rate (P<0.01) associated with a decreased peak velocity in early diastole without a concomitant increase in peak velocity during atrial systole in each of the myocardial regions. Furthermore, the AsyI was higher in the HCM group than in controls (19% versus 6%, respectively), and this index was inversely correlated with the PFR/SV (r=-0.86, P<0.001). The regional diastolic velocity of the myocardium at each of the four analyzed regions was not significantly different with verapamil, but the AsyI was significantly lower (P<0.05).


CONCLUSIONS
Children with HCM show abnormalities of both global and regional LV diastolic function. In these patients, chronic administration of verapamil plays a crucial role in the improvement in global LV filling and, as a consequence, in clinical manifestations. The beneficial effects of verapamil seem to be related to a reduction in diastolic asynchrony more than to significant changes in diastolic velocities of the myocardial fibres.
Pacileo
G
G
Second University, Naples, Italy. gpacile@tin.it
De Cristofaro
M
M
Russo
M G
MG
Sarubbi
B
B
Pisacane
C
C
Calabrò
R
R
D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002312:Cardiomyopathy, Hypertrophic / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D003971:Diastole / Q000187:drug effects*; D015150:Echocardiography, Doppler; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D016277:Ventricular Function, Left / Q000187:drug effects*; D014700:Verapamil / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D014700:Verapamil