Yasuyoshi Iwado

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: a study using oxygen 15–labeled water PET

BackgroundMyocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD.Methods and ResultsTwenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF) and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg · kg-1 · min-1) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perfusion abnormality (group C, n = 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 ± 0.54) than in group B (2.22 ± 0.87, P < .05), in group C (2.92 ± 1.21, P < .01), and in normal segments (3.86 ± 1.24, P < .001). CFR in group B was lower than in group C (P < .02) and in normal segments (P < .001). CFR in group C was lower than in normal segments (P < .02).ConclusionsAreas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.

Assessment of Coronary Function in Children With a History of Kawasaki Disease Using 15O-Water Positron Emission Tomography

Background—Coronary abnormalities after Kawasaki disease (KD) may be associated with endothelial dysfunction due to intimal hypertrophy. The purpose of this study was to evaluate myocardial flow reserve (MFR) and endothelial function in regressed aneurysmal regions after KD. Methods and Results—Subjects were 12 patients aged 16.0±2.6 years who suffered from KD at 1.7±1.5 years and 12 normal subjects aged 26.5±3.4 years. MFR and endothelial function were estimated, respectively, by changes in myocardial blood flow (MBF) during ATP infusion and by that during cold pressor test using 15O-water positron emission tomography. Data from 24 regressed aneurysmal regions were compared with those from the corresponding regions (n=36) in the control group. Although the MBF at rest in the regressed aneurysmal regions was similar to that in controls, the MBF at a hyperemic state induced by ATP infusion in the regressed aneurysmal regions was significantly lower than that in the control regions. Therefore, the MFR in regressed aneurysmal regions was significantly lower than that in controls (3.53±0.95 versus 4.60±1.14;P <0.05). MBF at rest and during the cold pressor test did not change in the control regions, but it was significantly reduced in regressed aneurysmal regions. The ratio of MBF during the cold pressor test to MBF at rest was significantly lower in regressed aneurysmal regions than in control regions (0.67±0.15 versus 1.00±0.15;P <0.05). Conclusions—MFR and endothelial function are often impaired in regressed aneurysmal regions after KD, and tomography enables the noninvasive evaluation of coronary function.

Visit-to-visit variability in blood pressure over a 1-year period is a marker of left ventricular diastolic dysfunction in treated hypertensive patients.

Although visit-to-visit variability in systolic blood pressure (SBP) has recently been demonstrated to be a strong predictor of stroke, there are no data about relationships between SBP variability and cardiac damage in hypertensive patients. We compared relationships between visit-to-visit variability in SBP and left ventricular (LV) diastolic dysfunction with the relationships between the mean SBP value and cardiac parameters in treated patients. Forty treated hypertensive patients (69±9 years of age) had their blood pressure measured at outpatient clinics every 1 or 2 months over a 1-year period. The standard deviation (s.d.) of SBP and the difference between the maximum and minimum SBPs during this year were calculated to assess visit-to-visit variability. The mean SBP during the year was also calculated. LV diastolic function was assessed by the ratio (E/A) of early (E) and late (A) diastolic transmitral flows, early diastolic mitral annular velocity (e′) and the ratio (E/e′) of E to e′ using Doppler echocardiography. E/A only correlated with the s.d. of SBP (r=−0.327, P=0.040), whereas e′ correlated with s.d. of SBP (r=−0.496, P=0.001) and maximum–minimum SBP difference (r=−0.490, P=0.001). E/e′ correlated with s.d. of SBP (r=0.384, P=0.014), maximum–minimum SBP difference (r=0.410, P=0.009), and the mean value of SBP (r=0.349, P=0.028). Multiple regression analysis demonstrated only the maximum–minimum SBP difference independently associated with E/e′ (β=0.410, P=0.009). Thus, the visit-to-visit variability of SBP showed better correlation with LV diastolic dysfunction than mean values of SBP. High visit-to-visit variability of SBP was associated with LV diastolic dysfunction and may constitute a high risk for diastolic heart failure in hypertensive patients.

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 no 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.

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.

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.

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.

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.

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.

Reduced Bone Mineral Density in Hypertensive Patients Is Associated with Left Ventricular Diastolic Dysfunction, Not Left Ventricular Hypertrophy

Left ventricular (LV) hypertrophy and diastolic dysfunction are commonly observed in hypertensive patients, and have been demonstrated to be risk factors of chronic heart failure due to LV diastolic dysfunction. Recently, reduced bone mineral density has been found in hypertensive patients compared with healthy controls. However, relationships between bone mineral density and LV hypertrophy and diastolic dysfunction have not been fully assessed. We examined relationships between bone mineral density and both LV hypertrophy and diastolic dysfunction in 38 hypertensive patients (23 males, 15 females; mean age 71 ± 8 y) who had been treated with antihypertensive drugs for at least 1 year. The bone mineral density of the calcaneus was measured with a quantitative ultrasound measurement device (A-1000 EXPRESS/InSight, GE Healthcare, Horten, Norway), and the stiffness index was determined as a parameter of bone mineral density. Echocardiography was performed to measure the left ventricular mass index as a parameter of LV hypertrophy. Left ventricular diastolic dysfunction was also assessed by early diastolic mitral annular velocity (e′), and the ratio of early transmitral flow velocity (E) to e′ (E/e′). The bone mineral density did not correlate with left ventricular mass index, but did correlate with e′ (r = 0.453, P < .01) and E/e′ (r = −0.359, P < .05). Thus, reduced bone mineral density in hypertensive patients is not associated with LV hypertrophy but with LV diastolic dysfunction. Hypertensive patients with reduced bone mineral density may have a high risk of chronic heart failure due to LV diastolic dysfunction as well as bone fractures due to osteoporosis.