Effect of intravenous administration of cibenzoline on left ventricular diastolic pressures in patients with hypertrophic cardiomyopathy: its relationship to transmitral Doppler flow profiles.

BACKGROUND: Cibenzoline is able to improve left ventricular (LV) diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM), but the exact mechanism remains to be determined. METHODS AND RESULTS: The present study was designed to elucidate the effect of intravenous administration of 1.4 mg/kg of cibenzoline on aortic and LV pressures, and transmitral Doppler flow pattern in 7 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 9 patients with hypertrophic nonobstructive cardiomyopathy (HNCM). Before and at the end of the administration, aortic and LV pressures, LV pressure gradient (LVPG) and transmitral Doppler velocity profiles were examined. After the administration of cibenzoline, LV minimal and end-diastolic pressures decreased from 9+/-4 mmHg to 1+/-5 mmHg (p=0.0049) and from 22+/-7 mmHg to 14+/-5 mmHg (p=0.0106) in patients with HOCM, and from 9+/-5 mmHg to 5+/-3 mmHg (p=0.0036) and from 20+/-6 mmHg to 14+/-3 mmHg (p=0.0033) in patients with HNCM. LVPG decreased in all patients with HOCM. E-wave velocity increased, A-wave velocity decreased, and thus the E/A ratio increased from 0.77+/-0.29 to 1.20+/-0.48 (p=0.0004). CONCLUSIONS: Reduction of LV diastolic pressures by intravenous administration of cibenzoline may be related to an improvement in the E/A ratio in patients with HCM.     

Antiarrhythmic drug, cibenzoline, can directly improve the left ventricular diastolic function in patients with hypertrophic cardiomyopathy.

The effect of cibenzoline on left ventricular diastolic function was investigated in patients with hypertrophic cardiomyopathy (HCM). Before and 2 h after an oral administration of 200 mg of cibenzoline, echocardiographic, apexcardiographic and gated radionuclide angiographic studies were performed in 12 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 7 with hypertrophic nonobstructive cardiomyopathy (HNCM). After administration of cibenzoline, the left ventricular pressure gradient decreased from 96+/-33 mmHg to 29+/-22 mmHg (<0.0001). Fractional shortening decreased from 53.3+/-7.5 to 45.4+/-6.2% (p=0.0008) in patients with HOCM and from 49.9+/-8.7 to 40.9+/-7.5% (p=0.0039) in patients with HNCM. On the other hand, E-wave velocity increased and A-wave velocity decreased in both groups. The time between the second heart sound and O point was shortened from 253+/-53 to 176+/-21 ms (p<0.0001) in patients with HOCM and from 245+/-54 to 185+/-44 ms (p=0.0050) in patients with HNCM. The time to peak filling rate was shortened from 248+/-79 to 190+/-40 ms (p=0.0072) in patients with HOCM and from 218+/-33 to 163+/-26 ms (p=0.0052) in patients with HNCM. These results indicate that in patients with HCM, cibenzoline suppresses left ventricular systolic function, but can markedly improve left ventricular diastolic dysfunction through its direct action.     

Doppler estimation of left ventricular filling pressures in patients with hypertrophic cardiomyopathy

BACKGROUND: Conventional Doppler parameters are unreliable for estimating left ventricular (LV) filling pressures in hypertrophic cardiomyopathy (HCM). This study was undertaken to evaluate flow propagation velocity by color M-mode and early diastolic annular velocity (Ea) by tissue Doppler 2 new indices of LV relaxation, combined with mitral E velocity for estimation of filling pressures in HCM. METHODS AND RESULTS: Thirty-five HCM patients (52+/-15 years) underwent LV catheterization simultaneously with 2-dimensional and Doppler echocardiography. Pulsed Doppler echocardiography of mitral and pulmonary venous flows was obtained along with flow propagation velocity and Ea. LV preA pressure had weak or no relations with mitral, pulmonary venous velocities and atrial volumes. In contrast, preA pressure related strongly to E velocity/flow propagation velocity (r=0.67; SEE=4) and E/Ea (r=0.76; SEE=3.4). In 17 patients with repeat measurements, preA pressure changes were well detected by measuring E velocity/flow propagation velocity (r=0.68; P=0.01) or E/Ea (r=0.8; P<0.001). PreA pressure estimation with these 2 methods was tested prospectively in 17 additional HCM patients with good results (E velocity/flow propagation velocity, r=0.76; E/Ea, r=0.82). CONCLUSIONS: LV filling pressures can be estimated with reasonable accuracy in HCM patients by measuring E velocity/flow propagation velocity or E/Ea. These ratios also track changes in filling pressures.     

Cibenzoline improves coronary flow velocity reserve in patients with hypertrophic obstructive cardiomyopathy

The effect of cibenzoline, a class-Ia antiarrhythmic drug, on coronary flow velocity reserve (CFVR) was examined in patients with hypertrophic cardiomyopathy using transthoracic Doppler echocardiography. Coronary flow velocity reserve was assessed in 11 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 12 patients with hypertrophic nonobstructive cardiomyopathy (HNCM), before and after the intravenous administration of cibenzoline (1 mg/kg). Coronary hyperemia was induced by an intravenous infusion of adenosine triphosphate and CFVR was calculated as the ratio of hyperemic to basal mean coronary diastolic flow velocity. At baseline, CFVR was significantly correlated with left ventricular outflow tract pressure gradient (LVPG) in patients with HOCM (r = 0.67, P < 0.03). In patients with HOCM, administration of cibenzoline significantly improved impaired CFVR (2.0 ± 0.8 to 3.0 ± 1.0, P < 0.001), and reduced LVPG (55 ± 30 to 23 ± 18 mmHg, P < 0.001), while CFVR remained unchanged in patients with HNCM (2.6 ± 0.9 to 2.9 ± 0.8, P not significant). Cibenzoline not only reduces LVPG but also improves CFVR in patients with HOCM. In addition left ventricular outflow obstruction plays an important role in impaired coronary circulation in patients with HOCM.     

Left ventricular ejection dynamics in hypertrophic cardiomyopathy and aortic stenosis: comparison with the use of Doppler echocardiography

Left ventricular ejection dynamics of 15 patients with hypertrophic cardiomyopathy (nine obstructive, six nonobstructive) were compared to those in 12 age-matched normal subjects and 10 patients with valvular aortic stenosis by means of combined two-dimensional and Doppler echocardiography. Doppler peak flow velocities in obstructive (HOCM, 2.5 +/- 1.3 m/sec) and nonobstructive (HNCM, 2.6 +/- 0.6 m/sec) hypertrophic cardiomyopathy, as well as in patients with aortic stenosis (AS, 3.6 +/- 1.3 m/sec) were significantly higher than in the normal population (1.0 +/- 0.2 m/sec; p less than 0.001 for all comparisons), but did not differ from each other. The HOCM patients had time to peak velocity (154 +/- 55.7 msec) that was higher than that in both HNCM (86 +/- 8.4 msec) and normal groups (84.5 +/- 8.9 msec; p less than 0.001 for both comparisons), but did not differ from those in AS (117 +/- 52.5 msec). The total ejection time did not differ between HOCM (348.2 +/- 91.1 msec) and AS (328.8 +/- 30.4 msec) groups, but was prolonged in HOCM compared to HNCM (198 +/- 21.0 msec) and normal groups (233 +/- 28.3 msec; p less than 0.001 for both comparisons). The normal and HNCM groups did not differ in time to peak or total ejection time measurements. The percent of flow velocity present in the initial third of the systolic velocity integral for HOCM (44.5% +/- 5.9) and HNCM (49.4% +/- 2.5) groups was greater than for normals (36.2% +/- 5.4; p less than 0.05 for both comparisons), but HOCM values did not differ from HNCM values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained improvement in left ventricular diastolic function after alcohol septal ablation for hypertrophic obstructive cardiomyopathy.

AIMS: Impaired diastolic function is responsible for many of the clinical features of hypertrophic cardiomyopathy. In patients with hypertrophic obstructive cardiomyopathy (HOCM) whose symptoms are refractory to medical therapy, alcohol septal ablation (ASA) reduces left ventricular (LV) outflow tract gradient, with short-term improvement in LV diastolic function. Little is known about the longer term impact of ASA on diastolic function. METHODS AND RESULTS: We evaluated LV diastolic function at baseline and 1- and 2-year follow-up after successful ASA. In 30 patients (58+/-15 years, 22 men) who underwent successful ASA, New York Heart Association class was lower at 1-year follow-up compared with baseline (3.0+/-0.5 to 1.5+/-0.7; P<0.0001). LV outflow tract gradient (76+/-37 to 19+/-12; P<0.0001), interventricular septal thickness (19+/-2 to 14+/-2; P<0.0001), and left atrial volume (26+/-5 to 20+/-4; P<0.0001) were decreased. Significant improvement in E-wave deceleration time, isovolumic relaxation time, early diastolic mitral lateral annular velocity (E'), mitral inflow propagation velocity (V(p)), ratio of transmitral early LV filling velocity (E) to early diastolic Doppler tissue imaging of the mitral annulus (E/E'), and E/V(p) were observed at 1 year following successful ASA. These changes persisted in the subset cohort (n=21) for whom 2-year data were available. CONCLUSION: Successful ASA for HOCM leads to significant and sustained improvement in echocardiographic measures of diastolic function, which may contribute to improved functional status after successful ASA.     

Gender-specific differences in left ventricular remodelling and fibrosis in hypertrophic cardiomyopathy: insights from cardiovascular magnetic resonance

BACKGROUND: Gender is an independent risk factor for heart failure mortality in hypertrophic cardiomyopathy (HCM). AIMS: To explore the interaction between gender, myocardial fibrosis and remodelling in HCM. METHODS: We studied 64 HCM patients (28 females, aged 51+/-16 years) categorized as non-obstructive (HNCM, n=31) or obstructive (HOCM, n=33) and 60 healthy subjects (31 females, aged 43+/-14 years). Cine imaging was performed to assess left ventricular volumes and mass. LV remodelling index (LVRI) was calculated. Extension of late gadolinium enhancement (LGE) was quantified. RESULTS: Females in the control group and in the HNCM group had a lower LVRI than males (control: 0.7+/-0.1 vs. 0.9+/-0.2 g/ml, p<0.002; HNCM: 1.1+/-0.2 vs. 1.5+/-0.5 g/ml, p<0.001). In contrast, HOCM females had a similar LVRI compared to males (1.8+/-0.5 vs. 1.7+/-0.4 g/ml, p=ns). Thus the increase in LVRI was more pronounced in females compared to males. LGE was noted in 70% of the patients. No relation was found between the presence or the quantity of myocardial fibrosis and gender in any of the patient subgroups. CONCLUSION: Our data suggest a disproportionate degree of remodelling in different forms of HCM depending on gender. Gender does not appear to influence the quantity of fibrosis as defined by LGE.     

Effect of cibenzoline on regional left ventricular function in hypertrophic obstructive cardiomyopathy

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.     

Left ventricular Doppler characteristics in first-degree relatives of patients with hypertrophic cardiomyopathy

Left ventricular (LV) diastolic function may be affected early in patients with hypertrophic cardiomyopathy (HCM), regardless of the phenotypic expression of the disease. The aim of the present study was to detect whether LV diastolic performance, evaluated by conventional Doppler echocardiography, is impaired in first-degree relatives of patients with phenotypically expressed HCM, who had no clinical, electrocardiographic, or echocardiographic signs of the disease. Twenty-two young adults having the previously described characteristics comprised the study population and 22 sex- and age-matched healthy individuals served as controls. The 2 groups were compared according to several echocardiographic parameters and the following diastolic function indices: peak velocity of E wave, representing early filling; peak velocity of A wave, representing late filling; ratio of peak early to peak late velocity (E/A); deceleration time of E wave; and LV isovolumic relaxation time. Slower deceleration time of transmitral early filling in first-degree relatives of patients with HCM (192 +/- 31 vs 149 +/- 31 msec, p < 0.001) was the only variable that significantly differentiated the 2 groups. This study shows that in healthy persons with a family history of HCM, Doppler-derived mitral filling pattern shifted toward that observed in HCM and the slower deceleration time may serve as an early sign of disease development.     

Relationship between outflow obstruction and left ventricular functional impairment in hypertrophic cardiomyopathy: a Doppler echocardiographic study

Left ventricular outflow tract (LVOT) obstruction is predictive of a worse outcome in hypertrophic cardiomyopathy (HCM). In a detailed Doppler echocardiographic study of 178 selected HCM patients, the group of patients (n = 73) with the obstructive form (resting peak gradient > or = 30 mmHg) presented more hypertrophy and poorer systolic and diastolic left ventricular (LV) functions than the HCM group (n = 105) without obstruction. LVOT peak gradient was positively correlated with hypertrophy (P < 0.0001) and negatively to tissue Doppler mitral annulus systolic (P = 0.0001) and early diastolic (P < 0.0001) velocities. The gradient significantly correlated with E/Ea ratio (r = 0.67; P < 0.0001). By multiple regression, LVOT gradient was related to E/Ea, LV maximal thickness and left atrial size. In comparison with patients without obstruction, patients with obstruction presented greater hypertrophy (P < 0.0001), lower systolic and early diastolic mitral annulus velocities (both P < 0.0001), higher E/Ea ratio (P < 0.0001) and higher global function index (P < 0.0001). In HCM, beyond the effects on hypertrophy, LVOT obstruction is an independent determinant of LV functional abnormalities.     

静脉注射美托洛尔对肥厚型心肌病左心室功能的影响

目的:应用频谱多普勒超声心动图技术,定量观测肥厚型梗阻性心肌病和肥厚型非梗阻性心肌病患者经静脉注射美托洛尔前后左心室功能和左心室流出道压力阶差的变化,并观察血流动力学的变化,探讨静脉注射美托洛尔对肥厚型心肌病左心室功能的影响。方法:应用PHILIPS-SONOS7500型彩色多普勒超声诊断仪,测量用药前和用药后10分钟肥厚型梗阻性心肌病组(n=33)和肥厚型非梗阻性心肌病组(n=26)患者左心室功能各指标,并监测用药过程中的血流动力学变化。结果:肥厚型梗阻性心肌病组患者用药后较用药前左心室舒张功能明显改善,左心室流出道(LVOT)明显增宽(P<0.05),左心室流出道压力阶差(LVOTPG)明显下降(P<0.05),EF值无明显变化(P>0.05);肥厚型非梗阻性心肌病组患者用药后较用药前上述各指标无明显变化(P>0.05)。两组的心率、收缩压、舒张压用药后较用药前均明显降低(P<0.05),有显著差异。结论:静脉注射美托洛尔能够快速改善肥厚型梗阻性心肌病组患者的左心室舒张功能,改善临床症状,明显减轻左心室流出道梗阻,降低压力阶差,明显降低两组的血压、心率,影响其血流动力学;而对肥厚型非梗阻性心肌病组患者无明显作用,对两组的收缩功能均无明显影响。     

肥厚性心肌病的心室造影特点

目的分析梗阻型肥厚性心肌病(HOCM)患者心室造影结果及形态学特征。方法纳入1995~2005年收治入院并接受心室造影和超声检查的74例确诊为肥厚型心肌病的患者。以左心室流出道与左心室压力差≥30 mmHg为梗阻型,30 mmHg为非梗阻型,将患者分为2组。比较其形态学和造影结果。结果 (1)入选74例患者,梗阻型14例(18.9%),其中收缩期前向运动6例(42.9%),冠心病3例(21.4%);非梗阻型60例(81.1%),其中11例合并冠心病(18.3%)。(2)超声显示室间隔增厚至(11.4±2.5)mm,左室后壁厚度(9.8±1.7)mm,左心室舒张末内径(48±5)mm,左心房内径(36±5)mm。(3)左室造影显示左室舒张末容积为(123±31)ml,左室收缩末容积为(27±11)ml,左心室射血分数(EF)为(78±6)%。(4)左心室造影形态学特征为梗阻型心室结构14例,其中正常5例;非梗阻型左心室结构60例,正常27例。结论非梗阻型肥厚性心肌病与HOCM左室舒张末内径、左室舒张末容积及左室收缩末容积、EF值,以及呈现正常形态的病例数等均无差异。     

超声声学定量技术对肥厚型心肌病患者右心室功能的评价

目的应用声学定量技术(AQ)评价非对称性肥厚型心肌病(包括梗阻性和非梗阻性)患者右室收缩与舒张功能。方法应用声学定量技术分别对2004年7月至2005年10月辽宁省人民医院27例肥厚型梗阻性心肌病(HOCM)患者、35例肥厚型非梗阻性心肌病(HNCM)患者和30例正常对照组人群的标准心尖四腔心切面观进行分析。结果与对照组相比,肥厚型心肌病(包括梗阻型和非梗阻型)右室峰值快速充盈率与右房峰值快速充盈率之比(PRFR/PAFR)、右室快速充盈容积与右房收缩充盈容积之比(RF/AF)明显减低(P<0.05)。而右心室收缩功能指标EF与正常组相比差异无显著性。结论AQ为定量评价肥厚型心肌病患者的右室功能提供了新的方法。     

多普勒组织成像评价肥厚型心肌病左室舒张功能

目的应用多普勒组织成像脉冲技术测量二尖瓣环舒张速度,以评价肥厚型心肌病左室舒张功能.方法对90例肥厚型心肌病患者及50例正常人进行常规超声心电图及多普勒组织成像检查,测量各房室内径,室壁厚度,射血分数及二尖瓣环各点舒张早期峰值速度(Ea)、舒张晚期峰值速度(Aa).两组指标比较采用成组t检验.结果肥厚型心肌病患者室间隔厚度(25.5±6.6)mm,左室后壁厚度(9.9±2.3)mm,左室内径(42.9±5.9)mm,左房内径(39.9±4.7)mm,LVEF(71.9±4.3)%,二尖瓣血流E/A为1.42±0.7.肥厚型心肌病患者Ea较正常人减低.Aa无明显差异.结论肥厚型心肌病左室长轴主动松弛功能较正常人减低.     

Tissue Doppler-derived indices predict exercise capacity in patients with apical hypertrophic cardiomyopathy

BACKGROUND: Although impaired left ventricular (LV) diastolic function is a prominent feature of hypertrophic cardiomyopathy (HCM), diastolic function and its relation to exercise capacity in apical HCM (ApHCM) has not been explored previously. This study was sought to determine the relationship between diastolic mitral annular velocities combined with conventional Doppler indexes and exercise capacity in patients with ApHCM. PATIENTS: Twenty-nine patients with ApHCM (24 men; mean age +/- SD, 57 +/- 10 years) underwent supine bicycle exercise with simultaneous respiratory gas analysis and two-dimensional and Doppler echocardiographic study. RESULTS: The mitral inflow velocities (early filling [E], late filling, and deceleration time) were traced and measured. Early diastolic mitral annular velocity (E') was measured at the septal corner of mitral annulus by Doppler tissue imaging (DTI) from the apical four-chamber view. Pro-brain natriuretic peptide (proBNP) was measured at the time of echocardiography using a quantitative electrochemiluminescence immunoassay. E/E' ratio correlated inversely with maximal oxygen uptake (Vo(2)max) [r = - 0.47, p = 0.0106]. There was a significant positive correlation between E' and Vo(2)max (r = 0.41, p = 0.024). However, no correlation was found between conventional two-dimensional, Doppler indices, and proBNP and Vo(2)max). Of all the echocardiographic and clinical parameters assessed, E/E' ratio had the best correlation with exercise capacity (r - 0.47) and was the strongest independent predictor of Vo(2)max by multivariate analysis (p = 0.0106). CONCLUSIONS: DTI-derived indexes (E', E/E' ratio), an estimate of myocardial relaxation and LV filling pressures, correlate with exercise capacity in patients with ApHCM, suggesting that abnormal diastolic function may be a factor limiting exercise capacity.     

Myocardial velocity gradient as a noninvasively determined index of left ventricular diastolic dysfunction in patients with hypertrophic cardiomyopathy

OBJECTIVES: We investigated the utility of the peak negative myocardial velocity gradient (MVG) derived from tissue Doppler imaging (TDI) for evaluation of diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Hypertrophic cardiomyopathy is characterized by impaired diastolic function with abnormal stiffness and prolonged relaxation. However, it remains difficult to evaluate these defects noninvasively. METHODS: Both TDI and conventional echocardiography were performed in 36 patients with HCM and in 47 control subjects. Left ventricular (LV) pressure was measured simultaneously in all HCM patients and in 26 controls. RESULTS: The peak negative MVG occurred soon after the isovolumic relaxation period during the initial phase of rapid filling (auxotonic relaxation). It was significantly smaller in HCM patients than in control subjects (2.32 +/- 0.52/s vs. 4.82 +/- 1.15/s, p < 0.0001); the cutoff value for differentiation between all HCM patients and 47 normal individuals was determined as 3.2/s. Both the left ventricular end-diastolic pressure (LVEDP) (19.6 +/- 6.1 mm Hg vs. 6.5 +/- 1.7 mm Hg, p < 0.0001) and the time constant of LV pressure decay during isovolumic diastole (tau) (44.0 +/- 6.7 ms vs. 32.1 +/- 5.5 ms, p < 0.0001) were increased in HCM patients compared with controls. The peak negative MVG was negatively correlated with both LVEDP (r = -0.75, p < 0.0001) and tau (r = -0.58, p < 0.0001). CONCLUSIONS: A reduced peak negative MVG reflects both prolonged relaxation and elevated LVEDP. The peak negative MVG might thus provide a noninvasive index of diastolic function, yielding unique information about auxotonic relaxation in patients with HCM.     

Circulating levels of insulin-like growth factor-1 and its binding proteins in patients with hypertrophic cardiomyopathy.

Insulin-like growth factor-1 (IGF-1) is important in the hypertrophic response of the myocardium, so the present study was designed to elucidate whether the circulating levels of IGF-1 and its binding proteins (IGFBPs) are related to the disease condition of patients with hypertrophic cardiomyopathy (HCM), in particular the occurrence of congestive heart failure (CHF). The study group comprised 124 patients with HCM and 15 healthy control subjects. The HCM patients were subdivided into 3 groups: 39 with hypertrophic obstructive cardiomyopathy (HOCM), 67 with hypertrophic non-obstructive cardiomyopathy (HNCM), and 18 with HCM and a history of CHF (HF-HCM, n=18). Serum levels of IGF-1 and IGFBPs (IGFBP-1 and -3) were compared between groups. IGF-1 levels were significantly higher in patients with HOCM and HNCM, and lower in patients with HF-HCM than in control subjects (p<0.0001, p<0.005, and p<0.05, respectively). IGFBP-1 levels were significantly higher in patients with HF-HCM than in the other 3 groups (p<0.0001 for all). The findings suggest that circulating levels of IGF-1 and IGFBP-1 are related to the extent of myocardial injury in patients with HCM.     

Amount of left ventricular hypertrophy determines the plasma N-terminal pro-brain natriuretic peptide level in patients with hypertrophic cardiomyopathy and normal left ventricular ejection fraction

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) is increased in patients with hypertrophic cardiomyopathy (HCM); however, the determinants of NT-proBNP level have not been clarified in HCM. HYPOTHESIS: This study was performed to determine the relationship between NT-proBNP levels and various echocardiographic variables of patients with HCM and normal left ventricular ejection fraction (LVEF). METHODS: We assessed plasma NT-proBNP levels and echocardiographic variables of 36 patients (19 men, 58 +/- 14 years) with HCM and an LVEF of > or = 55%. Echocardiographic variables measured were LV wall thickness, end-diastolic LV internal dimension (LVIDd) and volume (LVEDV), LV mass, and LV mass index (LV mass/body surface area, LVMI). Left ventricular outflow tract pressure gradient, transmitral E and A velocities, deceleration time (DT) of the transmitral E wave, and septal annular E' velocity were measured by Doppler technique. The relationship between echocardiographic variables and plasma NT-proBNP level was analyzed. RESULTS: The plasma NT-proBNP level was 775.2 +/- 994.2 pg/ml (range 33.1-4729.0 pg/ml). It showed positive correlations with LV end-diastolic septal thickness (r = 0.39, p = 0.010) and LVMI (r = 0.27, p = 0.050), while it revealed negative correlations with LVIDd (r = -0.44, p = 0.004), LVEDV (r = -0.44, p = 0.004) and DT(r = -0.31,p = 0.034). The NT-proBNP level was higher in the patients with than in those without LV diastolic dysfunction (p = 0.033) and was independently related to LVIDd (p = 0.001), LVMI (p = 0.006) and DT (p = 0.031) by multivariate analysis. CONCLUSION: In patients with HCM and normal LVEF, the amount of LV hypertrophy and LV diastolic dysfunction may exert a significant role in determining plasma NT-proBNP level.     

Left ventricular relaxation and filling abnormalities in patients with HOCM and left ventricular pressure overload (author's transl)]

In order to test the hypothesis that delayed mitral valve opening (MO) with regard to endsystolic dimension (t DS-MO) is specific for hypertrophic obstructive cardiomyopathy (HOCM), LV echograms of patients with different forms of LV hypertrophy due to chronic pressure overload (CPO; aortic stenosis + arterial hypertension, n = 24) and hypertrophic obstructive cardiomyopathy (n = 24) were recorded, digitized and compared with those of normals (N :n = 28(. In patients with HOCM (93 +/- 37 ms; p less than 0.0001) and CPO (66 +/- 31 ms; p less than 0.0001) the time t DS-MO was significantly delayed compared with N (13 +/- 15 MS), due to abnormal relaxation. This prolonged relaxation time resulted in an abnormal diameter increase (delta D) during the isovolumic relaxation phase (HOCM: 4.0 +/- 2.2 MM/CPO: 3.0 +/- 1.8 mm; p less than 0.0001/N:0.6 +/- 0.5 mm) and the rapid filling phase (HOCM 7.6 +/- 2.7 mm; p less than 0.0001/CPO 9.2 +/- 2.9 mm; p less than 0.05 / N: 10.7 +/- 2.2 mm). The echocardiographical signs of an abnormal relaxation are not specific for HOCM, they can be seen in different forms of secondary LV hypertrophy and are accompanied by changes in the diastolic filling pattern.     

Usefulness of mitral annular velocity in predicting exercise tolerance in patients with impaired left ventricular systolic function

Left ventricular (LV) diastolic function is 1 of the determinants of exercise tolerance. However, the relation between early diastolic velocity of the mitral annulus (Ea) obtained by tissue Doppler imaging and exercise tolerance is unknown in patients with impaired LV systolic function. To investigate the feasibility of evaluating exercise tolerance using tissue Doppler imaging, we studied 53 consecutive patients (mean age 58 +/- 14 years) with a LV ejection fraction of <50% (mean 37 +/- 9%). We measured the peak early diastolic velocity of transmitral flow (E) and Ea at the lateral border of the mitral annulus and then calculated the E/Ea ratio. After echocardiography, we measured the peak oxygen consumption and anaerobic threshold (AT) by cardiopulmonary exercise testing. Of all the echocardiographic parameters, the best correlation for AT was the E/Ea ratio (r = -0.74, p <0.001). Peak oxygen consumption correlated well with Ea and the E/Ea ratio (r = 0.64 and r = -0.68, respectively, p <0.001). The AT and peak oxygen consumption did not correlate with conventional Doppler indexes. Using an AT of 8 ml/min/kg as the cutoff to separate severe exercise intolerance from normal, mild, or moderate exercise intolerance, a receiver-operating characteristic curve showed that an E/Ea ratio of >11.3 had the best combination of sensitivity (88%) and specificity (86%). Exercise tolerance correlated with the E/Ea ratio in patients with impaired LV systolic function. In conclusion, the evaluation of LV diastolic function using tissue Doppler imaging is useful for predicting exercise tolerance in patients with heart failure.