Differences in left ventricular diastolic dysfunction between eccentric and concentric left ventricular hypertrophy in hypertensive patients with preserved systolic function.

Left ventricular (LV) hypertrophy (LVH) may be eccentric or concentric (2 × LV posterior wall thickness relative to LV end-diastolic dimension ≤ 0.42 or > 0.42, respectively). The LV diastolic function between age-matched hypertensive patients with eccentric and concentric LVH was compared in the present study. Echocardiography was used to measure LV mass index (LV mass/body surface area; LVMI) as an index of LVH. LV diastolic function was assessed by measurements of peak early transmitral flow velocity (E)/peak late transmitral flow velocity (A) (the E/A ratio), peak early diastolic mitral annular velocity (e') and the E/e' ratio. Although LVMI, E/A and e' did not differ between the two groups, E/e' was significantly higher (worse) in patients with concentric LVH (13.4 ± 5.4) than in those with eccentric LVH (11.1 ± 3.6). Among hypertensive patients with LVH, those with concentric LVH may, therefore, have more severe LV diastolic dysfunction than those with eccentric LVH even if their LVMIs, which reflect the degree of LVH, are similar.

Aortic root dilatation as a marker of subclinical left ventricular diastolic dysfunction in patients with cardiovascular risk factors.

Consensus is lacking about the clinical importance of aortic root dilatation in assessment of the risk of cardiovascular disease. In this study, correlations between aortic root diameter and echocardiographic features of left ventricular (LV) diastolic function were investigated in 333 patients with at least one cardiovascular risk factor (hypertension, diabetes or dyslipidaemia) and preserved LV systolic function. Aortic root diameter was measured by M-mode echocardiography, and LV diastolic function was evaluated by measuring the peak velocity of early (E) and late (A) diastolic transmitral blood flow and peak early diastolic mitral annular velocity (E') by Doppler echocardiography. Linear regression analysis showed that, in men, age was not related to aortic root diameter but hypertension and LV hypertrophy were, whereas the converse was true in women. The parameters E, E/A ratio and E', were related to aortic root diameter in both sexes. Stepwise multiple regression analysis confirmed that E in women and E' in men were independently associated with aortic root diameter. It is concluded that aortic root dilatation might be a useful marker of subclinical LV diastolic dysfunction. Patients with preserved systolic function showing aortic root dilatation should, therefore, be given preventative therapy against LV diastolic heart failure.

Transient left ventricular dysfunction in ischaemic myocardium after stress: comparative study with exercise and pharmacological stress gated myocardial single photon emission computed tomography.

In ischaemic heart disease patients, transient left ventricular dysfunction is observed due to post-exercise stunning. The aim of this study was to determine whether transient left ventricular dysfunction could also be seen after short-acting pharmacological stress (adenosine triphosphate). A 1 day rest/stress gated myocardial single photon emission computed tomography was performed on 362 patients suspected of having ischaemic heart disease by exercise (n=199) or short-acting pharmacological stress (n=163). Left ventricular ejection fraction were estimated both at rest and stress. Based on perfusion findings, patients were subdivided into ischaemia, fixed defect and normal group. For the ischaemia and fixed defect group, left ventricular ejection fraction after stress was significantly decreased compared with the resting value by exercise stress (ischaemia group, 57.5+/-11.0 vs 60.4+/-10.4; fixed defect group, 47.7+/-16.7 vs 49.6+/-16.8; P<0.01), but not by pharmacological stress (ischaemia group, 55.8+/-13.4 vs 57.1+/-13.8; fixed defect group, 50.8+/-13.5 vs 50.6+/-13.1; P=NS). In the normal group, left ventricular ejection fraction after stress was not significantly changed by either exercise (65.7+/-10.4 vs 66.8+/-10.2; P=NS) or pharmacological stress (63.0+/-11.7 vs 64.0+/-12.1; P=NS). It is concluded that a transient decrease in left ventricular ejection fraction after stress was observed following post-exercise, not following a short-acting pharmacological stress in patients showing perfusion abnormalities. Transient left ventricular dysfunction may be the result of post-exercise stunning, not from subendocardial hypoperfusion induced by short-acting pharmacological stress.

Ultrasonic tissue characterization can predict beta-blocker efficacy in dilated cardiomyopathy.

The aim was to determine if the combination of cyclic variation of myocardial integrated backscatter (variation IB) and left ventricular mass measurements can predict the efficacy of beta-blocker treatment in dilated cardiomyopathy. In 32 patients, left ventricular mass and variation IB were measured at baseline and during 6 microg/kg/min dobutamine infusion before the initiation of beta-blocker therapy. Variation IB was measured at left and right ventricular halves in the ventricular septum. The baseline left ventricular mass index and transseptal variation IB gradient during dobutamine were significantly greater in the effective group (1.16 +/- 0.18 g/mL and 1.8 +/- 0.6 dB) than in the ineffective group (0.94 +/- 0.28 g/mL, p = 0.032 and 0.4 +/- 0.6 dB, p < 0.005). When both baseline left ventricular mass index > or = 1.05 g/mL and transseptal variation IB gradient during dobutamine > or = 1.5 dB were defined as predictive criteria for the effective group, the sensitivity was 78% and the specificity was 86%. Analysis of transseptal variation IB during dobutamine may provide useful information predicting the efficacy of beta-blocker therapy in dilated cardiomyopathy.

Prevention of cerebral thromboembolism by low-dose anticoagulant therapy in atrial fibrillation with mitral regurgitation.

Controversy exists regarding the influence of mitral regurgitation (MR) on thromboembolic risk in patients with atrial fibrillation. We aimed to investigate retrospectively a reduction of risk for stroke due to MR in atrial fibrillation and to evaluate the effectiveness of low-intensity anticoagulation therapy. In 313 patients with atrial fibrillation, transthoracic echocardiography was performed and MR was graded. Between the groups with no or mild MR (n = 209) and with moderate or severe MR (n = 104), age, sex, treatment, history of diabetes, hypertension, hyperlipemia and mitral stenosis, and previous stroke were compared. No significant differences in clinical characteristics, treatment, or history were observed between the two groups. The incidence of thromboembolism was significantly higher in the group with no MR (48 patients [23%]) than in the group with MR (14 patients [13%], p < 0.05). In the MR group, previous stroke was frequently observed in patients without warfarin treatment (11 of 51 patients) compared with patients with low-dose warfarin treatment (international normalized ratio of 1.6-1.8) (3 of 53 patients, p < 0.05). Consequently, the thromboembolic event was markedly prevented by low-dose warfarin treatment.

Suppression of fatty acid metabolism after exercise stress in patients with no electrocardiographic ST segment shift during balloon angioplasty.

Although ST segment shift is a marker of myocardial ischemia, some patients have no ST segment shift during percutaneous transluminal coronary angioplasty (PTCA). The aim of this study is to investigate myocardial perfusion and metabolism in adaptation for ischemia using 201TI and 123I-BMIPP dual exercise stress myocardial single photon emission computed tomography (SPECT) (dual stress SPECT). In 28 patients with coronary artery disease, dual stress SPECT was performed 3 weeks before PTCA. Early and delayed images were obtained at 5 minutes and at 3 hours after termination of ergometer stress, respectively. During PTCA, 12-lead ECG was recorded, and a significant ST segment shift was defined as more than 1 mm elevation or a depression of the J-point at the first ballooning. No collateral circulation on the coronary angiogram or 201TI filling on the delayed images were observed on any of the target regions of PTCA. Patients were divided into 2 groups: with (Group A: n = 15) and without (Group B: n = 13) significant ST segment shift during PTCA. A redistribution of TI was observed in 14 (93%) of Group A and 10 (77%) of Group B patients. Incidence of BMIPP redistribution was significantly higher in Group B (11 [85%]) than in Group A (3 [20%]) (p < 0.05). Redistribution of BMIPP means suppression of fatty acid metabolism during exercise stress. Augmentation of glucose metabolism is speculated to be an energy source in ischemic preconditioning.

Effect of cibenzoline, a class ia antiarrhythmic agent, on left ventricular diastolic function in hypertrophic cardiomyopathy.

We aimed to investigate whether the improvement of left ventricular (LV) diastolic function by cibenzoline, a class Ia antiarrhythmic drug, in hypertrophic obstructive cardiomyopathy (HOCM) is due to LV afterload reduction or a primary lusitropic effect on LV. Twenty-three patients with hypertrophic cardiomyopathy (11; HOCM, 12; non-obstructive HCM; HNCM) were examined. Pulsed-wave Doppler, color M-mode and tissue Doppler echocardiography were performed before and 90 minutes after oral administration of cibenzoline (300 mg), and were compared with a treatment of bisoprolol (5 mg/day, 10 days). Early (E) and late diastolic LV inflow velocity, E flow propagation velocity (FPV) and early diastolic mitral annulus velocity (Ea) were measured. E/FPV and E/Ea were calculated as indices of LV filling pressure. LV outflow pressure gradients estimated using continuous-wave Doppler in HOCM markedly decreased after cibenzoline (83 +/- 42 to 40 +/- 33 mmHg, p < 0.005) and bisoprolol (44 +/- 40 mmHg, p < 0.005). Following cibenzoline, E/FPV and E/Ea were significantly decreased in both HOCM (1.75 +/- 0.53 to 1.32 +/- 0.28, p < 0.05, 18.9 +/- 6.2 to 14.8 +/- 5.0, p < 0.05, respectively) and HNCM (1.75 +/- 0.58 to 1.41 +/- 0.73, p< 0.05, 13.0 +/- 4.3 to 9.7 +/- 3.6, p< 0.01, respectively). Those in HNCM did not change by bisoprolol. Cibenzoline improved LV diastolic function in HCM, whereas bisoprolol did not affect it. Thus, the primary lusitropic effect of cibenzoline rather than LV after load reduction might have contributed to the improvement of diastolic function in HOCM.

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.

Quantitative evaluation of left ventricular regional wall motion using a real-time wall thickness curve system with two-dimensional echocardiography.

The real-time wall thickness curve system was newly developed for recording left ventricular (LV) wall thickening (WT) on a 2-dimensional echocardiogram recorded in an arbitrary direction because of the scarcity of quantitative data on wall motion change during dobutamine-induced ischemia. This study tested the feasibility of this system for quantitative evaluation of wall motion. In normal subjects, accuracy and reproducibility of measurements were evaluated by comparison with measurements on a conventional M-mode echocardiogram and examination of inter- and intraobserver variability. In 28 patients with coronary artery disease, percent systolic wall thickening (%WT) was measured during dobutamine infusion in incremental doses of 6 microg/kg/min, from 6 to 30 microg/kg/min. Percent change in %WT by dobutamine was compared with percent coronary stenosis derived from quantitative coronary angiography. Analysis of the mean difference and 95% confidence intervals demonstrated good accuracy and reproducibility: 0.0 mm and intervals of -0.5 to 0.5 mm in diastolic wall thickening of LV posterior wall (PW) between both methods, -1% and -4% to 2% in %WT of IVS and LVPW between both observers, and -1% and -3% to 2% in that between both measurements. During dobutamine infusion, the percent change in %WT was significantly correlated with percent stenosis (r = 0.75, p<0.0001). The WT curve system enabled us to assess regional wall function as %WT and was available for quantitative observation of wall motion change during pharmacologic intervention. This system may reduce the effects of heart movement and may be of great clinical benefit in evaluating regional wall function.

Quantitative analysis of myocardial response to dobutamine by measurement of left ventricular wall motion using omnidirectional M-mode echocardiography.

Although dobutamine stress echocardiography is important for assessing cardiac ischemia and viability, analysis of wall motion is qualitatively performed. We quantitatively evaluated left ventricular wall motion using a newly developed omnidirectional M-mode echocardiography that can depict the M-mode at the site of region of interest on the 2-dimensional image in real time, and established its usefulness for analyzing the myocardial response to dobutamine infusion. Dobutamine stress echocardiography with omnidirectional M-mode was performed in 57 patients with coronary lesions. In 38 of these patients, exercise stress single-photon emission computed tomographic thallium scintigraphy (Tl-201 SPECT) was performed. Endocardial excursion of 103 regions was measured from omnidirectional M-mode at baseline, low-dose (6 microg/kg/min), and at peak dose (30 microg/kg/min) dobutamine. A decrease and increase in wall excursion was scored (from -3 to 3) for a changes of every 2 mm, and a quantitative wall motion score (QWMS) was calculated as a summation of the scores from baseline to low dose and from low to peak doses. Quantitative coronary stenosis score (QCSS) was calculated as a summation of stenotic and collateral scores. The stenosis scores were graded as: 1 = 0% to 50%, 2 = 50% to 75%, 3 = 75% to 90%, 4 = 90% to 95%, 5 = 95% to 100%; collateral scores were graded as: -1 = poor collateral, -2 = good collateral. Based on the QWMS at each dose of dobutamine, the serial changes in wall motion were divided into 4 groups: augmented, biphasic, no change, and worsening. The QCSS was clearly different among these groups. QWMS was significantly correlated with QCSS (r = 0.657, p <0.001). The incidence of redistribution in Tl-201 SPECT was high in the region with low score of QWMS. In conclusion, omnidirectional M-mode is useful for quantitatively determining the grade of cardiac ischemia by assessing the serial change of ventricular wall motion during dobutamine infusion.

Identification of a carbohydrate-binding site in Physarum haemagglutinin I.

Carbohydrate-binding peptides from trypsin-digests of Physarum lectins (haemagglutinins I and II) were isolated by affinity column chromatography. The amino acid sequence of the peptide fragment from haemagglutinin I was determined to be 48TVHQSWY54. A similar amino acid sequence was found in the peptide fragment from haemagglutinin II, in which alignment of valine, histidine, tryptophan and tyrosine was identical. Deletion of the heptapeptide sequence (TVHQSWY) by site-directed mutation abolished the haemagglutinating activity. The replacement of Trp53 by alanine resulted in a complete loss of the haemagglutinating activity, suggesting that the tryptophan residue in the heptapeptide sequence is essential for carbohydrate binding.