Reduction of left ventricular pressure gradient due to cibenzoline therapy in a 16-year-old girl with hypertrophic obstructive cardiomyopathy

Abstract

A 13-year-old girl was referred for closer examination of electrocardiographic abnormalities. She had a Levine 2/6 systolic murmur (SM) and a fourth heart sound. Electrocardiography findings showed poor R progression from V1 to V4 and negative T waves in the II, III, and aVF leads. Approximately 3.2 years later, her SM increased to Levine 3–4/6. Echocardiography indicated mitral regurgitation and left ventricular pressure gradient (LVPG) of 18.5 mmHg, together with a notch on the systolic wave in the apexcardiogram. We concluded that the electrocardiographic abnormalities were caused by hypertrophic cardiomyopathy. Approximately 6 months later, her SM further increased to Levine 4–5/6, and the voltage on the electrocardiogram increased. In carotid pulse tracing, steep upstroke and deflated percussion wave due to mitral regurgitation were noted. The LVPG was approximately 102 mmHg, and systolic anterior movement was confirmed. After the oral administration of 200 mg of cibenzoline, the LVPG decreased to approximately 48 mmHg. Subsequently, 300 mg/day of cibenzoline was administered. The LVPG further decreased, and her symptoms improved.

Learning objectives

Clinical symptoms and left ventricular pressure gradient decrease can be ameliorated by cibenzoline therapy in patients with hypertrophic obstructive cardiomyopathy. This finding applies not only to adult patients but also to teen-aged patients.

Introduction

Left ventricular pressure gradient (LVPG) is closely related to the deterioration of clinical symptoms in patients with hypertrophic cardiomyopathy (HCM) [1]. Thus, it is important to decrease LVPG in the treatment of patients with hypertrophic obstructive cardiomyopathy (HOCM). Cibenzoline therapy is known to be useful in ameliorating LVPG in adult patients with HOCM [2]. However, thus far, there have been only few reports on the use of cibenzoline in teen-aged patients. In this paper, we report the administration of cibenzoline to a 16-year-old girl with HOCM who showed improvement in her HOCM symptoms and LVPG after the administration.

Case report

A 13-year-old girl was referred to our hospital for closer examination of electrocardiographic abnormalities. Her complaint was chest discomfort during long-distance running. Her family and medical histories were nothing of note. Her blood pressure was 106/60 mmHg, and heart rate was 60 beats per minute. Auscultation indicated a Levine 2/6 systolic murmur (SM) maximally heard at the cardiac apex. Chest radiography revealed no significant abnormalities. Electrocardiography showed poor R progression from V1 to V4 and V5R < V6R, and negative T waves on leads II, III, and aVF (Fig. 1A). In echocardiographic studies, left ventricular end-diastolic dimension (LVDd), interventricular septal wall thickness (IVST), LV posterior wall thickness (LVPWT), and left atrial dimension (LAD) were 36 mm, 7 mm, 7 mm, and 29 mm, respectively. Additionally, an increase in LV inferior thickness, especially in the systolic phase (Fig. 1B, indicated by yellow arrows) was confirmed.

Fig. 1.

Electrocardiographic and echocardiographic studies performed at the first medical examination (A and B), and mechanocardiographic and Doppler echocardiographic studies conducted 3.2 years after the first medical examination (C and D).

LV, left ventricle; RV, right ventricle; LA, left atrium; Ao, aorta; CPT, carotid pulse tracing; ACG, apexcardiogram; PCG, phonocardiogram.

Blood chemistry results were not significant, and the plasma level of brain natriuretic peptide was 59.2 pg/mL.

Therefore, we made a diagnosis of suspected HCM. She was a junior high school student, and hence, we checked her condition during the spring, summer, and winter vacations.

Clinical course

Her clinical symptoms remained unchanged at 3.2 years after the first medical examination, but her SM increased to Levine 3–4/6. As indicated in Fig. 1C, the notch on the systolic wave of the apexcardiogram, indicated by a black arrow, was confirmed. As shown in Fig. 1D, she had mitral regurgitation and an LVPG of 18.5 mmHg. At this time, we concluded that her electrocardiographic abnormalities were due to HCM. Thus, metoprolol (40 mg/day) was administered, and the patient was instructed not to perform high-intensity exercises.

Approximately 6 months later, the patient was almost free of clinical symptoms. Her blood pressure was 128/62 mmHg and heart rate was 66 beats per minute. Her SM increased to Levine 4–5/6, and an early systolic sound was heard. As shown in Fig. 2A, the voltages in almost all leads increased. Additionally, as shown in Fig. 2B, the A-wave of apexcardiogram, indicated by the black arrow, markedly increased, and a big fourth heart sound was confirmed (indicated by the red arrow). SM due to mitral regurgitation, shown by the yellow arrow, was also confirmed. In carotid pulse tracing, steep upstroke and deflated percussion wave due to mitral regurgitation, shown by the blue arrow, were noted. LVDd, IVST, LVPWT, and LAD were 42 mm, 11 mm, 10 mm, and 34 mm, respectively. Additionally, an LVPG increased and its value was approximately 102 mmHg (Fig. 3A), and the contact between systolic anterior movement (SAM) and interventricular septal wall was observed (Fig. 3C).

Fig. 2.

Electrocardiographic (A) and mechanocardiographic (B) studies conducted 3.8 years after the first medical examination.

CPT, carotid pulse tracing; ACG, apexcardiogram; ECG, electrocardiogram; PCG, phonocardiogram.

Fig. 3.

Doppler and M-mode echocardiograms obtained before (A and C) and after (B and C) cibenzoline administration.

ECG, electrocardiogram; PCG, phonocardiogram.

We persuaded the patient and her parents regarding admission in the hospital to decrease the LVPG. For the LVPG decrease, 200 mg of cibenzoline was orally administered. Two hours after the administration, LVPG decreased to approximately 48 mmHg (Fig. 3B), and SAM also decreased (Fig. 3D). Subsequently, 300 mg/day of cibenzoline was administered. Three months later, the LVPG decreased to 18 mmHg, and her symptoms improved.

Discussion

Our patient did not have asymmetric septal hypertrophy but had an LVPG of >100 mmHg and SAM. In this patient, abnormal findings of mitral leaflets, papillary muscles and chordae could not be found. So, the narrowing of outflow tract due to LV hypertrophy of inferior region seems to be related to the increase of LVPG. Electrocardiography reflects the characteristics of the region of LV hypertrophy. High voltages and negative T-waves in the II, III, and aVF leads in our patient seemed to reflect LV hypertrophy in the inferior region. Poor R progression from V1 to V4 must be the mirror images of this finding.

Patients with HOCM usually have two SMs (Fig. 2B): systolic ejection murmur (PCG1- PCG3) and systolic regurgitant murmur (PCG4). In this patient, as LVPG increased, both SMs increased. Early systolic sound produced by the contact between SAM and interventricular septal wall is also important [3], [4]. Usefulness of mechanocardiography in the diagnosis of HCM has been reported. A notch on the systolic wave and prolongation of the O point of apexcardiogram are specific markers of HCM [4].

The effect of cibenzoline on the left ventricle during the acute phase is as follows: the strong Na⁺ channel-blockade effect of cibenzoline results in decreased intracellular Na⁺ concentration ([Na⁺]i) in myocytes, which, in turn, triggers cardiac Na⁺/Ca²⁺ exchanger activation to increase [Na⁺]i, resulting in the reduction of [Ca²⁺]i. This reduction causes a decrease in LV fractional shortening. The decrease in LVPG may also be related to the reduction in [Ca²⁺]i. [Ca²⁺]i remained normal during the chronic phase, and the decrease in LV fractional shortening returned to normal, and the reduction in LVPG persisted [5]. The effect of 300 mg/day of cibenzoline on LVPG was almost the same as that of 200 mg of cibenzoline [6].

Declaration of competing interest

None declared.