J Cardiol 2006 Oct; 48（4）: 209 – 213

Cibenzoline Attenuates Coronary
Systolic Reversal Flow in a PatientWith Hypertrophic Obstructive
Cardiomyopathy: A Case Report
KeishiSAIHARA, MD

Shuichi HAMASAKI, MD, FJCC
YutakaOTSUJI, MD, FJCC

Takashi

YOSHITAMA, MD

Sanemasa

ISHIDA, MD

Tetsuro

KATAOKA, MD

Hideki OKUI, MD
Chuwa

TEI, MD, FJCC

Abstract ─────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────────
Effects of cibenzoline on coronary hemodynamics, especially systolic reversal flow, were assessed in a53-year-old man with hypertrophic obstructive cardiomyopathy by coronary flow study using a Dopplerguidewire. Intravenous administration of cibenzoline resulted in decreases in the pressure gradient（60 to0 mmHg）and systolic left ventricular pressure（162 to 126 mmHg）, and an increase in systolic arterial pressure（102 to 132 mmHg）. Furthermore, the systolic reversal flow observed at baseline was markedly diminished following administration of cibenzoline. Therefore, we speculate that cibenzoline reduces ventricularwall stress by diminishing the left ventricular obstruction that occurs with compression of the intramyocardial arteries. Cibenzoline-induced attenuation of coronary systolic reversal flow may be associated with theeffectiveness of cibenzoline for diminishing the left ventricular obstruction.
──────────────────────────────────────────────────────────────────────────────────────────────────────────────────────J Cardiol 2006 Oct ; 48（4）: 209−213

Key Words
Cardiomyopathies, hypertrophic obstructive
Coronary circulation
Doppler ultrasound guidewire
Drug administration cibenzoline

INTRODUCTION
The degree of left ventricular outflow tractobstruction correlates with prognosis in patientswith hypertrophic cardiomyopathy（HCM）. 1）
Cibenzoline administration resulted in attenuationof left ventricular outflow pressure gradients inpatients with hypertrophic obstructive cardiomyopathy（ HOCM）, which, in turn, is related to adecrease in myocardial contractility.2−4）
Measurement of phasic coronary flow dynamics

at baseline shows that compression of the intramural coronary bed, elevated peak diastolic coronary
flow velocity, and reduced peak systolic coronary
flow velocity are frequently observed in patientswith HOCM. Several studies have demonstrated
coronary systolic reversal flow in patients withHOCM.5−8）However, the effects of cibenzoline on
coronary hemodynamics and coronary flow velocity pattern have not been characterized.
The present case describes cibenzoline-induced
attenuation of systolic reversal flow in a patient──────────────────────────────────────────────
鹿児島大学大学院医歯学総合研究科 循環器・呼吸器・代謝内科学 : 〒 890−8520 鹿児島県鹿児島市桜ヶ丘 8−35−1
Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, Kagoshima
Address for correspondence : HAMASAKI S, MD, FJCC, Department of Cardiovascular, Respiratory and Metabolic Medicine,Graduate School of Medicine, Kagoshima University, Sakuragaoka 8−35−1, Kagoshima, Kagoshima 890−8520 ; E-mail :hamasksh@m.kufm.kagoshima-u.ac.jp
Manuscript received April 24, 2006 ; revised May 26, 2006 ; accepted May 31, 2006

209

210

Saihara, Hamasaki, Otsuji et alFig. 1 Echocardiograms
A : Parasternal long-axis echocardiogram. The interventricular septum thickness（between arrows）was
32 mm, and the thickness of the posterior wall was 30 mm（between arrowheads）. Concentric left ventricular hypertrophy and narrowness of left ventricular dimensions could be detected in this view.
B : M-mode echocardiogram of the mitral valve shows systolic anterior motion of the mitral valve（arrows）.

with HOCM.
CASE REPORTA 53-year-old man was hospitalized inNovember 2004 secondary to rotary vertigo andexertional dyspnea（New York Heart Association
functional class Ⅱ）. Blood pressure was 122/62mmHg, and a systolic ejection murmur（grade 3/6）
was heard at the fourth intercostal space at the left
sternal border. An S4 heart sound was also appreciated. Chest radiography demonstrated cardiomegaly with a cardiothoracic ratio of 63.5% andprominent right second and left fourth arches.
Electrocardiography showed sinus rhythm at
70 beats/min, left axis deviation（ − 66 °）, highvoltage in the left side of the heart, a QS pattern inleads Ⅴ3 to Ⅴ6, and inverted T-waves in Ⅰ, aⅤL,
and Ⅴ4 to Ⅴ6. Laboratory data were unremarkable
except for elevation of brain natriuretic peptide andatrial natriuretic peptide（ 462 and 160 pg/ml,respectively）. Echocardiography showed diffuse
and severe left ventricular hypertrophy and apicalasynergy（ejection fraction of 60%）. Thickness of
the interventricular septum was 30 mm, and that ofthe ventricular posterior wall was 32 mm（Fig. 1−A）. M-mode echocardiography showed systolic
anterior movement of the anterior mitral leaflet（Fig. 1−B）. Continuous wave Doppler echocardiography showed a peak flow velocity of
4.6 m/sec, and the systolic pressure gradient wascalculated as 84 mmHg throughout the left ventric-ular outflow tract. Coronary angiography revealed
no significant stenosis.
To assess the hemodynamic impact of the left
ventricular pressure gradient, left ventricular andaortic pressures were obtained at baseline and during cibenzoline administration. A 0.014-inch
Doppler guidewire was placed in the left anterior
descending coronary artery, and average peakvelocity was recorded continuously. Intravenous
administration of cibenzoline（30 mg）resulted indecreases in the pressure gradient（60 to 0 mmHg）
and systolic left ventricular pressure（ 162 to126 mmHg）
and an increase in systolic arterial pressure（102 to 132 mmHg ; Fig. 2）. Furthermore, thesystolic reversal flow observed at baseline wasmarkedly diminished following administration ofcibenzoline, whereas average peak velocity
decreased from 53 to 32 cm/sec（Fig. 3）and coronary artery diameter remained generally unchanged（3.3 vs 3.2 mm）. Left anterior descending coronary
artery coronary blood flow（CBF ＝ cross-sectional9）
area × average peak velocity × 0.5）also decreased from 107 to 76 ml/min.
DISCUSSION
In this case, administration of cibenzoline
induced decreased coronary blood flow, although
the aortic diastolic pressure was increased as shownin Figs. 2 and 3. There are several reasons for thisdiscrepancy. First, the aortic-left ventricular diastolic pressure and the time spent in diastole are theJ Cardiol 2006 Oct; 48（4）: 209 – 213

Systolic Reversal Flow and Cibenzoline

211Fig. 2 Pressure gradient between the left
ventricle and the ascending aorta
before（left）
and after administrationof cibenzoline（right）
Administration of cibenzoline resulted indecreases in the pressure gradient（60 to0 mmHg）
and systolic left ventricular pressure（162 to 126 mmHg）and an increase insystolic arterial pressure（102 to 132 mmHg）.
AoP ＝ aortic pressure ; LVP ＝ left ventricular pressure.

Control

After administrating cibenzoline

Fig. 3 Representative coronary flow velocity pattern before（left）
and after injection of 30 mg ofcibenzoline（right）
The systolic reversal flow（arrows in left）was markedly diminished following administration of cibenzoline（right）.

major determinants of coronary blood flow.
However, elevated diastolic aortic pressure does
not result in unneeded perfusion because ofautoregulation. Second, myocardial oxygen consumption can be estimated by myocardial mass,
wall stress, contractility, and heart rate. Out of thesefour determinants, wall stress and contractility weremarkedly diminished immediately after cibenzoline
administration, which might reduce coronary bloodJ Cardiol 2006 Oct; 48（4）: 209 – 213flow by sparing myocardial oxgen consumption.
Third, systolic reversal flow may be associated withthis discrepancy. Antegrade diastolic coronary
blood flow compensating for systolic reversal flow
might be returned to normal by cibenzoline administration.
This is the first case of cibenzoline-inducedchanges in average coronary artery peak velocity
patterns in a patient with HOCM. Systolic reversal

212

Saihara, Hamasaki, Otsuji et al

flow in patients with HCM has been reported5,6,8−10）
and was thought to be secondary to an increase insystolic-extravascular coronary bed compression
and to increased systolic perivascular resistancecaused by differences in cardiac muscle structure.5,6,11）The present study indicates that the left
ventricular outflow gradient magnitude and resultant changes in ventricular wall tension are related
to the coronary blood flow velocity pattern.
Cibenzoline has a negative inotropic andchronotropic effect.12）Left ventricular ejection timecorrelates with the severity of left ventricular pressure gradient in patients with HOCM.13）
Differences in left ventricular pressure gradientcorrelated with left ventricular ejection time index
before and after administration of cibenzoline.2）
Thus, the decrease in left ventricular ejection timeassociated with cibenzoline may be related todecreases in left ventricular outflow obstruction andto changes in left ventricular myocardial contractility.
Angiographic evidence suggests septal perforator
artery compression in hypertrophic cardiomyopathy
could result in proximal reversal of systolic bloodflow.14）This is consistent with the baseline observations in the present case. The systolic reversal
flow may be secondary to increased left ventricularpressure and decreased aortic driving pressure dur要

ing systolic ejections that encourage retrograde
flow from the septum and left anterior descending
artery. The release phase during cibenzoline administration was associated with return of the left ventricular pressure to basal levels, abolition of left
ventricular-aortic gradient, and normalization of thephasic coronary flow velocity pattern. In the present patient, cibenzoline-induced attenuation ofsystolic reversal flow resulted in decreases in peakleft ventricular pressure, left ventricular external
work, and coronary blood flow. Therefore, we speculate that cibenzoline reduces ventricular wallstress by diminishing the left ventricular obstruction that occurs with compression of the intramyocardial arteries.
Cibenzoline-mediated improvement in pressure
gradients between the left ventricle and ascending
aorta was found in a patient with obstructive hypertrophic cardiomyopathy. Cibenzoline administration also resulted in attenuation of coronary systolic
reversal flow in the left anterior descending artery,which may be associated with the responsiveness of
cibenzoline for reducing the left ventricularobstruction. Although the mechanism and generalizability of this phenomenon remain unclear, thiscase demonstrates the profound effects of cibenzoline on coronary regulation and myocardial contractility.
約

シベンゾリンが冠動脈収縮期逆流を減弱させることが検証された閉塞性肥大型心筋症の 1 症例
才原啓司

濱崎秀一

尾 辻豊

石田実雅

片岡哲郎

奥井英樹

吉 玉
鄭隆
忠 和

閉塞性肥大型心筋症におけるシベンゾリンの冠血流動態，とくに収縮期逆流に及ぼす影響について検討したところ，興味深い知見を示した症例を経験したので報告する．症例は 53 歳，男性で，ドップラーガイドワイヤーを用いて冠血流動態の検討を行った．シベンゾリンの静注により左室収縮期圧は 162 から 126 mmHg に減少し，左室と大動脈の収縮期圧較差は 60 から 0 mmHg にまで改善した．その結果，大動脈収縮期圧は 102 から 132 mmHg に増加した．さらに，シベンゾリンの投与により冠血流収縮期逆流は消失した．以上の所見より，シベンゾリンの効果発現の機序として，心室壁張力を軽減させることにより，左室大動脈圧較差を減少させると同時に心筋内動脈の圧排を軽減させることが関与していると考えられた．よってシベンゾリンによる冠動脈収縮期逆流の消失は，圧較差改善効果と関連していることが示唆される．

J Cardiol 2006 Oct; 48（4）: 209−213

J Cardiol 2006 Oct; 48（4）: 209 – 213

Systolic Reversal Flow and Cibenzoline

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