Kazushi Yukiiri

Improvement of Cerebral Blood Flow by Olprinone, a Phosphodiesterase-3 Inhibitor, in Mild Heart Failure

Cerebral blood flow (CBF) is reduced in heart failure (HF). For the treatment of acute HF, a phosphodiesterase-3 inhibitor, olprinone (OL), yields an increase in myocardial contractility and a decrease in arterial afterload. During a 15-min intravenous infusion of OL (0.2 µg/kg/min), regional CBF at 6 sites of each cerebral cortex was examined using technetium-99m-ethylcysteinate dimer brain SPECT in 18 HF patients and 7 age-matched normal subjects. The baseline CBF was significantly reduced in HF (43.0 ± 3.9 ml/min/100 g) compared to that in normal subjects (48.0 ± 4.6 ml/min/100 g, p < 0.01). The baseline CBF showed a significant negative correlation with the increase in CBF during the OL infusion in HF (r = –0.38, p < 0.01) and normal subjects (r = –0.65, p < 0.01). The percent increase in CBF was significantly greater in HF (13.7%) than in normal subjects (9.8%, p < 0.046). In patients with HF, the CBF of the cerebral cortex was decreased, but was increased by OL infusion.

Brain Natriuretic Peptide as a Surrogate Marker for Cardioembolic Stroke with Paroxysmal Atrial Fibrillation

Background: Cardioembolic stroke generally results in severer disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic from noncardioembolic stroke (atherothrombotic and lacunar stroke), whenever ischemic stroke patients have sinus rhythm at the time of presentation. Methods: In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic or noncardioembolic stroke and assessed whether this could provide a basis for differentiating cardioembolic stroke (especially due to paroxysmal atrial fibrillation) from noncardioembolic stroke. Our patient cohort consisted of 99 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005, to December 31, 2006. We excluded 23 patients with valve disease, heart failure, myocardial infarction or chronic renal failure. The mean age of the remaining 76 patients (51 males, 25 females) was 70.0 ± 10.1 years. Results: Thirty-six patients had cardioembolic stroke with atrial fibrillation (including permanent and paroxysmal atrial fibrillation); the remaining 40 had noncardioembolic stroke. The plasma brain natriuretic peptide was evaluated on the first morning after admission in all patients. In cardioembolic stroke with atrial fibrillation (permanent and paroxysmal atrial fibrillation), the plasma brain natriuretic peptide, ratio of peak early filling velocity to peak atrial systolic velocity (E/A) and left atrial diameter were significantly increased (p < 0.001), and the left atrial appendage flow was significantly decreased (p < 0.001), compared with noncardioembolic stroke. Analyzed in those 4 factors, cardioembolic stroke was strongly predicted with >95% accuracy assessed by plasma brain natriuretic peptide and left atrial appendage flow. Conclusion: From our results, it was suggested that the first-day brain natriuretic peptide and left atrial appendage flow measurements would be helpful in differentiating cardioembolic stroke with atrial fibrillation from noncardioembolic stroke.

Plasma brain natriuretic peptide as a surrogate marker for cardioembolic stroke

BackgroundCardioembolic stroke generally results in more severe disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic stroke from non-cardioembolic stroke (atherothrombotic stroke and lacunar stroke). In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic stroke or non-cardioembolic stroke, and assessed the prediction factors of plasma brain natriuretic peptide and whether we could differentiate between stroke subtypes on the basis of plasma brain natriuretic peptide concentrations in addition to patients clinical variables.MethodsOur patient cohort consisted of 131 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005 to December 31, 2007. The mean age of patients (43 females, 88 males) was 69.6 ± 10.1 years. Sixty-two patients had cardioembolic stroke; the remaining 69 patients had non-cardioembolic stroke (including atherothrombotic stroke, lacunar stroke, or the other). Clinical variables and the plasma brain natriuretic peptide were evaluated in all patients.ResultsPlasma brain natriuretic peptide was linearly associated with atrial fibrillation, heart failure, chronic renal failure, and left atrial diameter, independently (F4,126 = 27.6, p < 0.0001; adjusted R2 = 0.45). Furthermore, atrial fibrillation, mitral regurgitation, plasma brain natriuretic peptide (> 77 pg/ml), and left atrial diameter (> 36 mm) were statistically significant independent predictors of cardioembolic stroke in the multivariable setting (Χ2 = 127.5, p < 0.001).ConclusionIt was suggested that cardioembolic stroke was strongly predicted with atrial fibrillation and plasma brain natriuretic peptide. Plasma brain natriuretic peptide can be a surrogate marker for cardioembolic stroke.

Comparison of central blood pressure and cardio-ankle vascular index for association with cardiac function in treated hypertensive patients

Recent automated applanation tonometry can measure radial pulse wave-derived central blood pressure (CBP), which has shown a prognostic value independently of peripheral blood pressure. However, CBPs clinical significance has not been fully established. We examined the associations between CBP and cardiac structure and function by comparing them with those of arterial stiffness assessed by cardio-ankle vascular index (CAVI) in treated hypertensive patients. Enrolled in the study were 102 patients (71±7 years) with treated hypertension. The transmitral early-to-atrial velocity ratio (E/A), peak systolic (S′), early diastolic (E′) mitral annular velocities and the Tei index were measured as indexes of cardiac function derived from conventional and tissue Doppler echocardiography. Left ventricular mass index (LVMI) was measured as an index of LV hypertrophy. CBP and CAVI were measured just after echocardiographic examination. CBP, but not CAVI, correlated with LVMI (r=0.306, P<0.01). Although CBP correlated only with the Tei index (r=0.201, P<0.05), CAVI correlated with E/A (r=−0.387, P<0.001), S′ (r=−0.270, P<0.01), E′ (r=−0.362, P<0.01) and the Tei index (r=0.339, P<0.01). Stepwise regression analysis revealed that neither CBP nor CAVI was independently associated with E/A, S′ or E′. However, CAVI, but not CBP, was independently associated with the Tei index (β coefficient=0.311, P<0.001), reflecting both LV systolic and diastolic function. In conclusion, CBP may be suitable for detecting LV hypertrophy. In contrast, CAVI may be suitable for detecting LV dysfunction. This difference, suggesting the clinical value of each parameter, should be kept in mind when we use CBP and CAVI for assessing arteriosclerosis in treated hypertension.

Echocardiographic Assessment of the Cardio-Renal Connection: Is Left Ventricular Hypertrophy or Diastolic Function More Closely Correlated with Estimated Glomerular Filtration Rate in Patients with Cardiovascular Risk Factors?

Although left ventricular (LV) hypertrophy and diastolic function assessed by echocardiography and chronic kidney disease (CKD) have been established as predictors of cardiovascular events in hypertensive patients, the relationships between the echocardiographic parameters and renal function have not been fully examined. We examined which echocardiographic parameter correlates best with estimated glomerular filtration rate (eGFR) in patients with cardiovascular risk factors. Enrolled in the study were 309 patients (mean age 67 ± 13 y) with cardiovascular risk factors. Echocardiography was performed to measure left ventricular mass index (LVMI) as an index of LV hypertrophy. Transmitral early to atrial velocity (E/A) ratio and peak early diastolic mitral annular velocity (E′) were measured as indexes of LV diastolic function. E/E′ was calculated as a parameter of LV preload. eGFR was measured using the equation proposed by the Japanese Society of Nephrology. The correlations of LVMI (r = −0.333, p < 0.001) and hypertension (r = −0.326, p < 0.001) to eGFR were closer than those of E′ (r = 0.276, p < 0.001) and E/A (r = 0.224, p < 0.001) to eGFR. Stepwise regression analysis showed that hypertension (β coefficient = −0.211, p < 0.001) and LVMI (β coefficient = −0.206, p < 0.001) were independently associated with eGFR. The E/E′ increased with a decrease in eGFR, and E/E′ in CKD stage 5 (16.0 ± 6.8) was significantly higher than that in patients in whom eGFR ≥ 90 mL/min/1.73 m2 (10.5 ± 4.5) (p < 0.001). Left ventricular diastolic function may be influenced by the increase in LV preload due to progression of CKD stage. Therefore, LV hypertrophy may be superior to LV diastolic dysfunction in predicting low eGFR in patients with CKD using echocardiography.

Influences of Hypertension and Diabetes on Normal Age-Related Changes in Left Ventricular Function as Assessed by Tissue Doppler Echocardiography

Although the impact of hypertension (HT) and type 2 diabetes mellitus (DM) on left ventricular (LV) function has recently been studied using tissue Doppler echocardiography (TDE), there are few studies discriminating between the impact of the disease and that of normal aging on LV function. The purpose of the present study was to elucidate the LV function in patients with HT and DM in various age strata in order to assess the independent roles of HT and DM on normal age-related changes in cardiac function. The population of the study consisted of four groups: 20 control subjects (Control), 20 patients with hypertension alone (HTN), 20 patients with type 2 diabetes alone (DM), and 20 patients with both hypertension and diabetes (HTN+DM) in each of five age strata—the 40s, 50s, 60s, 70s, and 80s. The strain and strain rate, which reflected both LV systolic and diastolic function, were assessed by TDE. The strain and strain rate decreased with advancing age in healthy control subjects and in all the patient groups. The strain and strain rate in the HTN group and the DM group showed lower values than those in the healthy control subjects in each age stratum. Furthermore, the strain and strain rate in the HTN+DM group showed the lowest values among all four groups in each age stratum. These results indicate that LV function as assessed by TDE demonstrates age-related deterioration with normal aging. Although HT or DM affects normal age-related changes in LV function, the co-existence of HT and DM has a more harmful effect on the normal age-related changes than HT alone or DM alone.

Contrast Harmonic Power Doppler Imaging of Congenital Ventricular Diverticulum A Case Report

A case of an 81-year-old woman with a left ventricular diverticulum who underwent myocar dial contrast echocardiography is reported. After administration of the contrast agent, a pulsed Doppler flow measurement clearly revealed the biphasic waveform of the ejection flow in the pre-systolic and systolic phase at the ostium of the diverticular cavity. A harmonic power Doppler image showed that part of the diverticulum wall had similar acoustic proper ties to the ventricular septal wall. Intracardiac blood flow and myocardial perfusion could be clearly evaluated and a ventricular diverticulum was correctly diagnosed using contrast echocardiography.

Effects of combined olmesartan and pravastatin on glucose intolerance and cardiovascular remodeling in a metabolic-syndrome model

Hypertension and dyslipidemia frequently coexist in patients with progressive insulin resistance and thus constitute metabolic syndrome. We sought to determine the merits of combining an angiotensin II receptor blocker and a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor in treating this pathological condition. Five-week-old Otsuka Long–Evans Tokushima Fatty rats, a model of metabolic syndrome, were untreated or treated with olmesartan 3 mg kg−1 per day, pravastatin 30 mg kg−1 per day or their combination for 25 weeks. Long–Evans Tokushima Otsuka rats served as normal controls. The antihypertensive effect of olmesartan and the lipid-lowering properties of pravastatin were both augmented by the combination. The oral glucose tolerance test revealed that only the combined treatment significantly reduced the area under the time–glucose curve, which was accompanied by augmented adiponectin messenger RNA expression in epididymal adipose tissue. Although the total cardiac endothelial nitric oxide synthetase (eNOS) content did not significantly differ among the groups, the combined treatment significantly increased the content of dihydrofolate reductase, a key eNOS coupler. Dihydroethidium staining of the aorta showed that the combination most significantly attenuated superoxide production. Moreover, Azan–Mallory staining revealed that the combination most significantly limited the perivascular fibrosis and wall thickening of intramyocardial coronary arteries. In conclusion, the combination of olmesartan and pravastatin augmented adiponectin expression in white adipose tissue and improved glucose tolerance in a rat model of metabolic syndrome, which was associated with more significant ameliorations of cardiovascular redox state and remodeling than those by treatments with either agent alone.

Quantitative assessment of coronary stenosis by harmonic power Doppler with a simple pulsing sequence and vasodilator stress in patients.

OBJECTIVES We examined whether myocardial contrast echocardiography (MCE) with harmonic power Doppler (HPD) employing a simple ultrasound pulsing sequence enables estimation of the severity of coronary artery stenosis in patients. BACKGROUND Contrast intensity (CI) during MCE with intravenous microbubble infusion is dependent on the myocardial blood flow velocity (MBFV) and pulsing interval (PI). METHODS Based on an in vitro experiment, we devised the MBFV index calculated as the reciprocal of the magnitude of CI decay produced by abrupt PI shortening during intermittent imaging. In 68 coronary artery territories from 49 patients, myocardial HPD images were acquired during intravenous infusion of Levovist, while the long PI with 1:10 electrocardiographic gating was shortened to 1:1, both at baseline and during adenosine triphosphate infusion. The MBFV index in each coronary territory and MBFV reserve as the ratio between hyperemia and baseline were compared with the severity of corresponding coronary artery stenosis assessed by quantitative coronary angiography (QCA) or by pressure guide wire as the fractional flow reserve (FFR). RESULTS Both the MCE-derived MBFV index during hyperemia and MBFV reserve exhibited significant negative correlations with the QCA-derived stenosis severity (r = -0.56 and r = -0.64, respectively). The MBFV reserve positively correlated with FFR (r = 0.89). By combining the cutoff values of the MBFV index during hyperemia and MBFV reserve, > or =75% of stenoses defined by QCA were determined, with a sensitivity of 77.3%, specificity of 93.4%, and accuracy of 88.3%. CONCLUSIONS Shortening of PI during intravenous MCE with intermittent HPD imaging under vasodilator stress enables assessment of coronary artery stenoses in patients.

Potential pitfalls of visualization of myocardial perfusion by myocardial contrast echocardiography with harmonic gray scale B-mode and power Doppler imaging

Objective: The present study compared the regional variation of myocardial signal intensity in visualizing myocardial perfusion by myocardial contrast echocardiography (MCE) between harmonic gray scale and power Doppler imaging. Methods: MCE was performed in 12 patients by electrocardiographic (ECG)-gated intermittent triggered MCE with harmonic gray scale and power Doppler imaging following slow intravenous injection of 0.5 ml contrast agent (Optison®). The interval between the ECG triggers (pulsing interval) was increased from every heart beat (1:1) to every 2 (1:2), 4 (1:4), and 8 (1:8) cardiac cycles to allow incremental microbubble (contrast agent) replenishment. The MCE images were recorded when attenuation produced by the left ventricular cavity was minimal. The background-subtracted videointensity was measured in 7 segments in an apical 4-chamber view: 3 (apical, mid, and basal) septal segments, 3 (apical, mid, and basal) lateral segments, and 1 apex segment (apical cap). Results: The background-subtracted videointensity for each segment was greater with the power Doppler than the gray scale imaging (p < 0.01). With the gray scale imaging, the background-subtracted videointensity in the basal septal segment demonstrated a negative value at all pulsing intervals, and the value (−9 ± 13) was significantly lower than that (22 ± 20) in the apical lateral segment at a pulsing interval of 1:8 (p < 0.01). With power Doppler imaging, the background-subtracted videointensity was high even in the basal septal segment (112 ± 33), and no significant difference was observed among each segment. Conclusions: The findings indicate that quantitative assessment of myocardial perfusion based upon background-subtracted videointensity may be difficult in the far field with harmonic gray scale imaging although the attenuation is not apparent by visual analysis. Harmonic power Doppler is more sensitive for detecting basilar perfusion in the far field compared with harmonic gray scale imaging.