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

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.

Impact of cibenzoline treatment on left ventricular remodelling and prognosis in hypertrophic obstructive cardiomyopathy.

AIMS: This study aimed to elucidate the long-term effect of cibenzoline therapy on cardiovascular complications and prognosis in patients with hypertrophic obstructive cardiomyopathy (HOCM). METHODS AND RESULTS: Eighty-eight patients with HOCM were treated with cibenzoline (Group A), and 41 patients did not receive cibenzoline (Group B). The changes in left ventricular (LV) remodelling, incidences of cardiovascular complications and deaths, were examined. The mean follow-up period was 15.8 ± 5.6 years in Group A and 17.8 ± 7.2 years in Group B. In Group A, the LV pressure gradient (LVPG) decreased immediately after treatment, and the reduction was maintained throughout the study. In Group B, the LVPG decreased gradually according to the deterioration of LV function. LV reverse remodelling was confirmed in Group A, and LV remodelling advanced in Group B. In Group A, the incidence of each cardiovascular complication was <10%. Only one patient experienced LV heart failure (LVHF). LVHF incidence and atrial fibrillation were higher in Group B than those in Group A (P < 0.0001). The incidence of death was 20.5% in Group A and 90.2% in Group B (P < 0.0001). The most frequent cause of death was sudden cardiac death (SCD) (38.9%) in Group A and LVHF (67.6%) in Group B. The incidence of SCD showed no significant difference between the two groups. The cumulative cardiac survival rate was higher in Group A than that in Group B (P < 0.0001). CONCLUSIONS: Cibenzoline treatment significantly reduced all cardiovascular complications and death due to LVHF and may be a promising treatment in patients with HOCM.

Predicting the clinical course in hypertrophic cardiomyopathy using thallium-201 myocardial scintigraphy.

AIMS: This study aimed to evaluate the changes in left ventricular remodelling with time in patients with hypertrophic cardiomyopathy (HCM) using thallium-201 myocardial scintigraphy. METHODS AND RESULTS: Forty-eight patients with HCM participated in the study. The extent score (ES) and a newly devised index termed the 'mean count change' (MCC) were used to evaluate the myocardial perfusion defects. Using the amount of thallium-201 uptake (TU), MCC (%) was calculated using the following formula: (last TU - initial TU)∕initial TU × 100. To confirm the site of the lesion, the left ventricle was divided into five segments: anterior, septal, inferior, lateral, and apex. Cardiovascular complications and deaths were recorded. The mean follow-up period was 8.6 ± 2.0 years. ES increased from 17.4 ± 13.7% to 44.0 ± 22.3% (P < 0.0001). MCC increased from 0% to 12.0 ± 9.0% (P < 0.0001). The apex was the most frequent site of lesion. Twenty-seven patients (56.3%) had experienced left ventricular heart failure (LVHF). Both ES and MCC were greater in patients with LVHF than in those without LVHF. An overlap between the two groups was greater in ES than in MCC. Patients with LVHF had a higher incidence of atrial fibrillation and apoplexy. Nineteen patients (39.6%) died during the study period; 14 died from LVHF, 3 from sudden cardiac death, and 2 from cancer. CONCLUSIONS: Thallium-201 myocardial scintigraphy is useful for detecting the severity of myocardial damage and for confirming the lesion site in patients with HCM. MCC may be superior to ES in the evaluation of these changes with time.

Coronary artery-left ventricular shunt: an important cause of chest pain in patients with hypertrophic cardiomyopathy.

The influence of shunts between the coronary artery (CA) and the left ventricle (LV), on chest pain (CP) in patients with hypertrophic cardiomyopathy (HCM) is unknown. We examined the incidence of CA-LV shunts and their influence on CP in HCM patients. Twenty normal control subjects (NCS), 3 with CP due to CA-LV shunts (CP patients), and 60 with HCM participated. Interventricular septal wall thickness (IVST), LV posterior wall thickness (LVPWT), cardiac and stroke indexes (CI and SI), LV end-diastolic pressure (LVEDP), and proximal diameters of the CA were measured. Twenty-five HCM patients had a CA-LV shunt (41.7%). Both IVST and LVPWT were greater in the HCM patients than in NCS and CP patients. These values showed no significant differences between the HCM with shunt and HCM without shunt groups. CI and SI were lower in the HCM patients than in NCS and CP patients. LVEDP was higher in the HCM and CP patients than in NCS. CA diameters were larger in the HCM and CP patients than in NCS. CP was found in 32 HCM patients (53%). The incidence of CP was greater in the HCM with shunt group than in HCM without shunt group (80 vs. 34%, p < 0.0005). There was no significant difference in CA diameters between the HCM patients with CP and those without CP. CA-LV shunts are often found in HCM patients and are closely related to CP. Thus, CA-LV shunts are an important factor behind CP in HCM patients.

Plasma levels of atrial and brain natriuretic peptides in apparently healthy subjects: Effects of sex, age, and hemoglobin concentration.

BACKGROUND: To examine whether the use of one value of natriuretic peptides to define "normal" is appropriate in all individuals, and to assess the influence of sex, age, and other variables on atrial and brain natriuretic peptides (ANP, BNP) levels. METHODS AND RESULTS: A total of 1375 apparently healthy people (women:155, men:1220), aged 18-70years were enrolled. Both ANP and BNP levels were higher in women than in men (ANP: 12.50±6.82pg/mL vs 8.18±4.19pg/mL; BNP: 9.85±7.63pg/mL vs 7.03±6.97pg/mL). The subjects were divided into three age groups: group I, 18-30years; group II, 30-50years; group III, 50-70years. First, the influence of age on ANP and BNP levels was examined. In women, both ANP and BNP levels were higher in groups II and III than those in group I. In men, ANP and BNP levels increased with age. Second, sex differences in ANP and BNP levels due to age were examined. ANP level was higher in women than that in men in all age groups. BNP level was higher in women than that in men in groups I and II. Multivariate analysis indicated that both ANP and BNP levels were influenced by age, hemoglobin level, and platelet counts. CONCLUSION: Because ANP and BNP levels in healthy subjects are influenced by sex, age, and hemoglobin levels, the use of a single value to define "normal" in all individuals is not appropriate.

Elevated Cardiac Enzymes in Hypertrophic Cardiomyopathy Patients With Heart Failure - A 20-Year Prospective Follow-up Study.

BACKGROUND: To better understand the evolution of typical hypertrophic cardiomyopathy (HCM) to heart failure (HF), we investigated the relationship between serum biochemical abnormalities and changes in left ventricular (LV) remodeling. METHODS AND RESULTS: Seventy-seven HCM patients were followed for 20 years. Creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), LDH-1, troponin T and myosin light chain-1 (MLC-1) were measured. Abnormal CK-MB elevation was observed in 64% of HCM patients. LDH-1 was not significantly different compared with the control subjects. Troponin T elevation was observed in 3 HCM patients and MLC-1 elevation was not observed. According to median CK-MB, HCM patients were divided into 2 groups: group H (CK-MB ≥2.5%, n=33) and group L (CK-MB <2.5%, n=44). During the follow-up period in group H, LV end-diastolic dimension increased (P<0.0001), fractional shortening decreased (P<0.0004), and left atrial dimension increased (P<0.0001). The markers reflecting LV hypertrophy were significantly decreased. In group L, LV end-diastolic dimension increased (P<0.02) and left atrial dimension increased (P<0.0001). HF was observed in 18 patients in group H and in 4 in group L. There were 14 HF deaths in group H and 2 in group L, and 3 sudden cardiac deaths in group H. CONCLUSIONS: Persistent elevation of cardiac enzymes in HCM patients indicates ongoing myocardial injury, ultimately resulting in death by HF.

Impact of chronic use of cibenzoline on left ventricular pressure gradient and left ventricular remodeling in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: Cibenzoline, a class Ia antiarrhythmic drug, is useful for reducing the left ventricular pressure gradient (LVPG) in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, chronic effects of cibenzoline on LVPG and left ventricular (LV) remodeling are unknown. METHODS: Forty-one patients with HOCM participated in this study. Echocardiographic, electrocardiographic, and brain natriuretic peptide (BNP) data collected before and after cibenzoline treatment were compared. From the relation between LVPG and plasma concentration of cibenzoline, an efficacious plasma concentration of cibenzoline was estimated. RESULTS: The mean follow-up period was 74.2±47.1 months. The LVPG decreased from 104.8±62.6mmHg to 27.6±30.5mmHg (p<0.0001). The LV end-diastolic dimension increased from 42.8±5.8mm to 46.2±5.4mm (p<0.0001), but neither LV end-systolic dimension nor LV fractional shortening changed significantly. The left atrial dimension decreased from 40.0±4.7mm to 36.2±5.1mm (p<0.0001). The E-wave velocity/A-wave velocity ratio increased, early diastolic annular velocity (Ea) increased, and E/Ea ratio decreased. The interventricular septal wall thickness, LV posterior wall thickness, the Sokolow-Lyon index, and the depth of negative T wave decreased. The heart rate-corrected QT interval was shortened. Plasma BNP level decreased from 418.8±423.7pg/ml to 213.7±154.1pg/ml (p<0.02). The safe and efficacious plasma concentration of cibenzoline was between 300ng/mL and 1500ng/mL. CONCLUSIONS: Long-term treatment with cibenzoline attenuated LVPG, improved LV diastolic dysfunction, and induced LV hypertrophy regression in patients with HOCM without causing serious complications.

Association Between Genetic Variation in the SCN10A Gene and Cardiac Conduction Abnormalities in Patients With Hypertrophic Cardiomyopathy.

Arrhythmias are associated with reduced quality of life and poor prognosis in patients with hypertrophic cardiomyopathy (HCM). Recent genome-wide association studies revealed that a nonsynonymous single nucleotide polymorphism, rs6795970, in the SCN10A gene was associated with the PR interval. We examined whether the PR prolonging allele (A allele) in the SCN10A gene may be associated with cardiac conduction abnormalities in HCM patients.We genotyped the polymorphism in 149 HCM patients. Conduction abnormalities were defined as first-degree heart block, bundle-branch block, and bifascicular heart block. Patients were divided into two groups: group A consisted of 122 patients (82%) without a conduction abnormality; and group B consisted of 27 patients (18%) with one or more cardiac conduction abnormalities. The frequency distribution of the SCN10A genotypes (G/G, G/A, and A/A) among the patients with HCM was 71%, 26%, and 3%, respectively. A cardiac conduction abnormality was documented in 9% with G/G and 40% with G/A or A/A. There was a significant difference in the genotype distribution between the two groups (P = 0.0002). In the dominant A allele model, there was a significant difference in genotypes between the two groups (P < 0.0001). In addition, the A allele remained significant after adjusting for other covariates in a multivariate model (odds ratio = 6.30 [95% confidence interval: 2.24 to 19.09], P = 0.0005).The rs6795970 in the SCN10A gene, which is reported to carry a high risk of heart block, might be associated with cardiac conduction abnormalities in HCM patients.

[Anticoagulant therapy with dabigatran in elderly patients ≥80 years of age with atrial fibrillation].

AIM: Atrial fibrillation is a potent risk factor for stroke, and the administration of anticoagulant therapy is important for preventing thromboembolism. Dabigatran is the first new oral anticoagulant developed as an alternative to warfarin. However, serious major gastrointestinal bleeding events have been observed in elderly patients in post-market case reports. We therefore retrospectively investigated elderly cases of the use of anticoagulant therapy with dabigatran. METHODS: Twenty-eight patients over 80 years of age were treated with anticoagulant therapy at our satellite hospital. Nine of the patients received dabigatran, and all others received warfarin. We evaluated the CHADS2 score, HAS-BLED score, renal function and incidence of adverse effects in nine patients treated with dabigatran. RESULTS: All of the nine patients received 220 mg/day of dabigatran, with no antiplatelet agents. Seven patients continued to receive dabigatran. One patient had an impaired renal function (Cr 1.55 mg/dl, Ccr 30 ml/min). However, the activated partial thromboplastin time (APTT) was not prolonged and neither major bleeding nor stroke were noted in seven patients. Although two patients were unable to continue dabigatran treatment due to APTT prolongation, no serious complications were observed during the administration of dabigatran. CONCLUSIONS: No serious adverse effects of dabigatran anticoagulant therapy were detected in our elderly patients. Although it is necessary to monitor the risk of bleeding, renal dysfunction, effects of drug combination and so on, some elderly patients with atrial fibrillation are good candidates for dabigatran treatment.

Advances in medical treatment of hypertrophic cardiomyopathy.

We reviewed the natural history of patients with hypertrophic cardiomyopathy (HCM). The effect of medical treatments on natural history, left ventricular (LV) functions and LV remodeling was also evaluated. Sudden cardiac death and end-stage heart failure are the most serious complications of HCM. Age <30 years and a family history of sudden premature death are risk factors for sudden cardiac death in HCM patients. End-stage heart failure is not a specific additional phenomenon observed in patients with HCM, but is the natural course of the disease in most of those patients. After the occurrence of heart failure, the progression to cardiac death is very rapid. Young age at diagnosis, a family history of HCM, and greater wall thickness are associated with a greater likelihood of developing end-stage heart failure. Neither beta-blockers nor calcium antagonists can prevent this transition. The class Ia antiarrhythmic drugs, disopyramide and cibenzoline are useful for the reduction of LV pressure gradient. Unlike disopyramide, cibenzoline has little anticholinergic activity; therefore, this drug can be easily adapted to long-term use. In addition to the reduction in LV pressure gradient, cibenzoline can improve LV diastolic dysfunction, and induce regression of LV hypertrophy in patients with HCM. A decrease in intracellular Ca(2+) concentration through the activation of the Na(+)/Ca(2+) exchanger associated with cibenzoline therapy is likely to be closely related with the improvement in HCM-related disorders. It is possible that cibenzoline can prevent the progression from typical HCM to end-stage heart failure.

Impact of septal curvature on regional strain in patients with hypertrophic cardiomyopathy.

BACKGROUND: The interventricular septum in hypertrophic cardiomyopathy (HC) has a unique shape, which is characterized by the convex curvature toward the left ventricle (LV). The aim of this study was to examine the relationship between curvature of the LV wall and regional myocardial strain. METHODS AND RESULTS: Fifty-six patients with HC (mean age, 55±12 years) and 20 age- and sex-matched control subjects (mean age, 56±8 years) were enrolled. The curvature index (1/radius) was measured by drawing along the endocardial surface from the apical 4-chamber and short axis views. Peak systolic strain was calculated in the septal and lateral walls using 2-D speckle tracking echocardiography. The septal curvature index and septal longitudinal strain were significantly lower in the HC group than in the control group. A multivariate model using the HC patient data showed that the septal curvature index and septal thickness were the independent determinants of septal longitudinal strain (septal curvature index: ß=-0.421, P<0.001; septal thickness: ß=0.401, P=0.002). In addition, global longitudinal strain and E/e' were worse in the lower septal curvature index group compared with the higher group. CONCLUSIONS: Septal longitudinal strain is associated with the degree of septal curvature. This indicates a possible link between LV wall configuration and regional myocardial function.

Impact of synergistic polymorphisms in adrenergic receptor-related genes and cardiovascular events in patients with dilated cardiomyopathy.

BACKGROUND: Sustained cardiac adrenergic stimulation has been implicated in the progression of cardiovascular events in patients with dilated cardiomyopathy (DCM). Our group hypothesized that a combination of polymorphisms that result in increased synaptic norepinephrine release and enhanced receptor function would predispose patients with DCM to cardiovascular events. The effect of polymorphisms in adrenergic receptor-related genes on cardiovascular event-free survival in patients with idiopathic DCM was evaluated. METHODS AND RESULTS: Genotyping at 3 loci (ADRB1 Ser49Gly and Arg389Gly, and NET T-182C) was performed in 83 patients with DCM. Patients were followed prospectively to the endpoint of cardiovascular events (mean follow-up, 45 months). Cardiovascular events were defined as cardiac death and emergent hospitalization as a result of congestive heart failure, arrhythmia, and cerebrovascular events. Analyses were conducted based on the number of predicted risk genotypes a patient carried. The ADRB1 Ser49 allele carrier, ADRB1 Arg389 allele carrier, and NET-182CC genotype were defined as the predicted risk genotypes. Cardiovascular event-free survival was compared based on the number of predicted risk genotypes. Cardiovascular event-free survival was significantly better in patients with fewer than 3 predicted risk genotypes than in those with 3 predicted risk genotypes. CONCLUSIONS: Genotyping at these 3 loci might be a useful approach for identification of patients with DCM at risk for cardiovascular events.

Clinical significance of global two-dimensional strain as a surrogate parameter of myocardial fibrosis and cardiac events in patients with hypertrophic cardiomyopathy.

AIMS: Late gadolinium enhancement (LGE) on contrast-enhanced magnetic resonance imaging (MRI) in hypertrophic cardiomyopathy (HCM) has been reported to be associated with myocardial fibrosis and cardiac events. In patients with HCM, two-dimensional (2D) strain can identify subclinical global systolic dysfunction despite normal left ventricular (LV) chamber function. Therefore, this study tested the hypothesis that global 2D strain could detect subtle myocardial fibrosis and serve as a novel prognostic parameter in HCM patients. METHODS AND RESULTS: Echocardiography and MRI were performed in 48 consecutive patients with HCM and normal chamber function. We measured global longitudinal strain (GLS) in apical two-chamber, four-chamber, and long-axis views using speckle-tracking analysis. The extent of LGE (%LGE = LGE volume/total LV volume) and LV mass index were calculated by MRI using Simpson's rule and custom software. All patients were followed up for major cardiac events. Global longitudinal strain in patients with LGE was significantly lower than that without LGE (-11.8 ± 2.8 vs. -15.0 ± 1.7%, P < 0.001). Multivariate analysis showed that GLS was an independent predictor of %LGE (standard coefficient = 0.627, P < 0.001). During a mean follow-up period of 42 ± 12 months, five patients had cardiac events. When the patients were stratified based on the median level of GLS (-12.9%), all events were observed in the worse GLS group (P = 0.018). CONCLUSION: These results suggest that global 2D strain might provide useful information on myocardial fibrosis and cardiac events in HCM patients with normal chamber function.

Risk for atrial fibrillation in patients with hypertrophic cardiomyopathy: association with insulin resistance.

BACKGROUND: We undertook a cross-sectional study to test the hypothesis that patients with hypertrophic cardiomyopathy (HCM) who have impaired left ventricular (LV) diastolic function are insulin resistant. We also evaluated the relation between the development of atrial fibrillation (AF) and insulin resistance (IR) in patients with HCM. METHODS AND RESULTS: Eighty-eight patients with HCM (71 men, 17 women) were enrolled in the study. IR was estimated using the homeostasis model assessment (HOMA) index. Echocardiographically determined left atrial (LA) dimension was measured as a marker of LA size. The ratio of trasmitral early LV filling velocity to early diastolic mitral annulus velocity (E/e') was also measured as a marker of LV diastolic function. Twenty-seven patients (31%) had IR. Multivariate logistic regression analyses showed that independent determinants of AF were increased LA size [odds ratio (OR) 3.5, 95% confidence interval (CI) 1.2-9.8] and impaired LV diastolic function [OR 4.6, 95% CI 1.6-12.8]. The strongest determinant of LA size was the HOMA index (p = 0.0005). Similarly, the HOMA index (p = 0.0019) was an independent determinant of LV diastolic function. CONCLUSION: IR is highly prevalent among non-diabetic patients with HCM. A possible mechanism by which IR affects the development of AF is mediated through its association with increased LA size or impaired LV diastolic function. IR may be an important underlying mechanism for the genesis of AF in HCM.

Usefulness of the MOSAIC (measurement of stenosis by aliasing coronary flow) method using transthoracic color Doppler echocardiography in unstable angina patients.

BACKGROUND: The aim of this study was to investigate the significance of the MOSAIC (measurement of stenosis by aliasing coronary flow) method for the detection of proximal left coronary stenosis in patients with unstable angina (UA) using transthoracic Doppler echocardiography (TTDE). METHODS: Patients (n=107) with UA were evaluated. Proximal left coronary flow was sought in the short axis (SAX) at the aortic root level using color Doppler guidance. When detected coronary flow showed color aliasing, the color velocity range was gradually increased until color aliasing nearly disappeared. Then, the color baseline was shifted until the color flow showed "isovelocity". RESULTS: Proximal coronary flow was detected in 86 (80.4%) of 107 patients. In these 86 patients, an optimal cutoff value of isovelocity ≥ 47.5 cm/s predicted significant coronary stenosis (percent diameter stenosis ≥ 70%) of the proximal left anterior descending (AHA segment 6) or left main coronary artery with a sensitivity of 88%, specificity of 97%, positive predictive value of 98%, and negative predictive value of 86%. In all 107 patients, the same cutoff value predicted significant coronary stenosis with a sensitivity of 78%, specificity of 98%, positive predictive value of 98%, and negative predictive value of 81%. CONCLUSIONS: The MOSAIC method may play a complementary role in expeditious risk stratification and decision making in patients with UA.

The differences in left ventricular torsional behavior between patients with hypertrophic cardiomyopathy and hypertensive heart disease.

BACKGROUND: The aim of this study was to investigate the differences in left ventricular (LV) twisting behavior between patients with hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD). METHODS: Forty-four patients with HCM (mean age, 63±15 years), 35 patients with HHD (mean age, 63±13 years) and 20 age and sex-matched control subjects were evaluated. After a standard echocardiographic examination, LV twist and twisting velocity profiles from apical and basal short-axis images were analyzed using two-dimensional speckle tracking imaging. RESULTS: LV diastolic and systolic dimensions, and ejection fraction were not significantly different among the groups. LV mass index and early diastolic mitral annular velocity were not significantly different between the HCM and HHD groups. The peak torsion in the HCM and HHD groups was significantly greater than that in the control group. The peak untwisting velocity in the HCM group was comparable with that in the control group. However, when the peak untwisting velocity was corrected by peak torsion, this ratio was significantly decreased in the HCM group compared with the values in the HHD and control groups. The time to peak untwisting velocity in the HCM group was significantly longer than the values in the HHD and control groups. CONCLUSIONS: These results suggest that enhanced peak torsion in HCM may improve untwisting behavior, but this mechanism fails to fully compensate for impaired untwisting behavior compared with HHD.

Myocardial fibrosis attenuates the effect of cibenzoline on left ventricular diastolic function in patients with hypertrophic cardiomyopathy.

The aim of this study was to investigate the relationship between late gadolinium enhancement (LGE) and the effect of cibenzoline (CBZ) on left ventricular (LV) diastolic function in hypertrophic cardiomyopathy (HCM) patients. Echocardiography before and after intravenous CBZ (1.4 mg/kg over 5 minutes) and magnetic resonance imaging (MRI) were performed in 22 consecutive patients with HCM [mean age: 65 ± 14 years, obstructive HCM: 14, nonobstructive HCM (HNCM): 8]. The extent of LGE (%LGE = LGE volume/total LV volume) was obtained by contrast-enhanced MRI using custom software. LGE was observed in 19 patients (mean %LGE = 5.1% ± 3.9%). The propagation velocity of LV early filling flow (Vp) increased significantly in patients with obstructive HCM (26 ± 7 to 36 ± 14 cm/s, P = 0.001) and nonobstructive HCM (25 ± 9 to 36 ± 16 cm/s, P = 0.007). A significant negative correlation was observed between the change in Vp and %LGE in patients with HCM (r = 20.542, P = 0.009). Less extensive myocardial fibrosis, as demonstrated by LGE on contrast-enhanced MRI, may predict the ability of CBZ to improve LV diastolic function in HCM.

Pharmacogenetic interactions between Angiotensin-converting enzyme insertion/deletion polymorphism and response to cibenzoline in patients with hypertrophic obstructive cardiomyopathy.

Cibenzoline, a Class I antiarrhythmic agent, can attenuate the left ventricular pressure gradient (LVPG) in patients with hypertrophic obstructive cardiomyopathy (HOCM). An association between the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene and the progression of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy has been reported. The aim of this study was to investigate the pharmacogenetic interactions between the ACE insertion/deletion polymorphism and the response to cibenzoline in patients with HOCM. Twenty-four patients with HOCM participated in this study. The LVPG and left ventricular function were measured by echocardiography before and 2 hours after administration of a single oral dose of 200 mg cibenzoline. The ACE insertion/deletion polymorphism was genotyped. The frequencies of the genotypes D/D, D/I, and I/I were 16%, 42%, and 42%, respectively. Before administration of cibenzoline, the LVPG was higher in patients with the D allele than in those without it (105 +/- 47 mm Hg versus 64 +/- 24 mm Hg, P = 0.0195). After administration of cibenzoline, the LVPG significantly decreased to 41 +/- 27 mm Hg in those with the D allele (P = 0.0001) and to 33 +/- 24 mm Hg in those without it (P = 0.0003). The LVPG in patients with the D allele was significantly decreased by cibenzoline when compared with patients without the allele (64 +/- 45 mm Hg versus 31 +/- 17 mm Hg, P = 0.038). Patients with HOCM with the ACE D allele had a high LVPG. Cibenzoline was more effective in patients with HOCM with the ACE D allele.