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Effect of cibenzoline on regional left ventricular function in hypertrophic obstructive cardiomyopathy
I Kondo1, K Mizushige, S Nozaki
1Second Department of Internal Medicine, Kagawa Medical University, Japan.
Insights
Cibenzoline improved left ventricular (LV) outflow obstruction in hypertrophic obstructive cardiomyopathy (HOCM) by normalizing asynchronous contractions in the LV posterior wall, not the septum. This suggests a potential therapeutic mechanism for HOCM treatment.
Area of Science:
- Cardiology
- Biomedical Engineering
- Pharmacology
Background:
- Hypertrophic obstructive cardiomyopathy (HOCM) is characterized by left ventricular (LV) outflow tract obstruction.
- Cibenzoline, a class Ia antiarrhythmic drug, is used to alleviate this obstruction.
- The precise mechanism of cibenzoline's action in HOCM remains debated.
Purpose of the Study:
- To investigate the effects of cibenzoline on regional LV function.
- To assess changes in myocardial acoustic properties using ultrasonic integrated backscatter.
- To elucidate the mechanism of LV outflow obstruction relief in HOCM.
Main Methods:
- Utilized ultrasonic integrated backscatter to measure wall thickening (%WT) and cyclic variation of integrated backscatter (mag-CVIBS).
- Assessed contractile element asynchrony via phase difference between CVIBS and %WT in the LV posterior wall.
- Measured LV outflow tract pressure gradients using continuous-wave Doppler echocardiography in 10 HOCM patients and 16 controls.
Main Results:
- Cibenzoline reduced %WT in the LV posterior wall but not in the interventricular septum (IVS).
- Baseline phase difference was higher in HOCM patients, indicating greater asynchrony.
- Cibenzoline normalized the phase difference in the LV posterior wall and significantly decreased LV outflow tract pressure gradients.
Conclusions:
- Cibenzoline alters regional myocardial function and acoustic properties in the LV posterior wall of HOCM patients.
- Normalization of the phase difference in the LV posterior wall correlates with reduced LV outflow tract pressure gradients.
- The therapeutic effect of cibenzoline in HOCM may stem from negative inotropy and improved synchrony in the LV posterior wall, rather than the IVS.
Background:
Cibenzoline, a class Ia antiarrhythmic drug, can be used to relieve left ventricular (LV) outflow obstruction in hypertrophic obstructive cardiomyopathy (HOCM). However, the mechanism of this agent in HOCM has been controversial.
Hypothesis:
This study was designed to investigate the effect of cibenzoline on regional LV function and the acoustic properties in HOCM using ultrasonic integrated backscatter.
Methods:
Ten patients with HOCM and 16 healthy volunteers were examined. In patients with HOCM, wall thickening (%WT) and the magnitude of cyclic variation of integrated backscatter (mag-CVIBS) in the interventricular septum (IVS) and LV posterior wall were measured before and after oral administration of cibenzoline. To assess asynchrony of contractile elements, the phase difference between CVIBS and %WT were measured from the LV posterior wall. Pressure gradients at the LV outflow tract were estimated using continuous-wave Doppler echocardiography.
Results:
Although %WT decreased significantly in the LV posterior wall, %WT and mag-CVIBS remained unchanged in the IVS. The phase difference in the LV posterior wall was significantly greater in patients with HOCM than in healthy volunteers (HOCM:healthy volunteers, 1.57 +/- 0.23:1.00 +/- 0.03, p < 0.001) at baseline. After administration of cibenzoline, the phase difference shifted to normal value (from 1.57 +/- 0.23 to 1.28 +/- 0.27, p = 0.0382), and pressure gradients at the LV outflow tract decreased (from 109 +/- 55 to 58 +/- 48 mmHg, p = 0.0063). Changes in pressure gradients at the LV outflow tract and the phase difference were closely related.
Conclusions:
Regional function and the acoustic properties of myocardium in HOCM were altered by cibenzoline in the LV posterior wall but remained unchanged in the IVS. The normalization of the phase difference in the LV posterior wall was closely related to the decrease in pressure gradients at the LV outflow tract. These findings suggest that negative inotropic action and the improvement of asynchrony in the LV posterior wall rather than in the IVS may contribute to the reduction of pressure gradients at the LV outflow tract in HOCM.