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 (beta coefficient = -0.211, p < 0.001) and LVMI (beta 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 > or = 90 mL/min/1.73 m(2) (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.

Early detection of hypertension in a patient treated with sunitinib by measuring cardio-ankle vascular index.

Cardio-ankle vascular index (CAVI) has been established as a marker of arterial stiffness, which is increased in hypertensive patients. CAVI reflects the stiffness of the aorta, femoral artery, and tibial artery. Sunitinib, multi-targeted tyrosine kinase inhibitor with both anti-angiogenic and anti-tumor activities, has been proved effective in patients with gastrointestinal stromal tumors. However, the treatment with sunitinib is often complicated by side effects such as hypertension. We describe an 84-year-old woman with gastrointestinal stromal tumor, who showed changes in arterial stiffness preceding the appearance of hypertension in the early phase after sunitinib initiation. The patient received sunitinib (50 mg given daily) for gastrointestinal stromal tumor. We assessed the influence of sunitinib on arterial stiffness every 7 days by measuring CAVI. The CAVI, which reflects arterial stiffness, was increased from 9.95 at baseline to 11.65 at 7 days after the initiation of sunitinib, whereas the blood pressure remained unchanged (117/72 and 119/76 mmHg). At 14 days after sunitinib initiation, the blood pressure was increased to 159/89 mmHg, indicating the occurrence of hypertension, while the CAVI was 11.90, the similar level detected at 7 days. Subsequently, sunitinib treatment was discontinued, because of the marked decrease in blood platelets. Both blood pressure and CAVI, together with blood platelets, were restored to the baseline values at 12 days after cessation of sunitinib. In conclusion, the increase in the CAVI preceded the appearance of sunitinib-induced hypertension. Arterial stiffness assessed by CAVI may be useful for early detection of sunitinib-induced hypertension.

Decline of plasma brain natriuretic peptide during enzyme replacement therapy in a female patient with heterozygous Fabry's disease.

There are no data regarding changes in plasma brain natriuretic peptide (BNP) levels in patients with Fabry's diseases during enzyme replacement therapy (ERT). We describe a patient with Fabry's disease who demonstrated the improvement in plasma brain BNP levels in response to ERT. Fabry's disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A, which results in progressive intracellular accumulation of globotriaosylceramide (Gb3) in various organs including the heart. Cardiac involvement is frequent in Fabry's disease, resulting in cardiac dysfunction due to hypertrophic changes of the myocardium and thickening of the valves. Although ERT has been reported to improve cardiac function, no consensus has been reached regarding the effectiveness of ERT in female patients with heterozygous Fabry's disease. We report a 44-year-old woman having heterozygous Fabry's disease, who showed mitral valve thickening and regurgitation on echocardiogram. ERT was performed by intravenous infusion of recombinant alpha-galactosidase A every 2 weeks. We assessed the influences of ERT on cardiac function by measuring echocardiograhic parameters and monitoring BNP levels, which show treatment-induced drop in patients with heart failure. Although her cardiac function and mitral regurgitation assessed by echocardiography had not improved 18 months after the beginning of ERT, the plasma BNP level, which was 91.5 pg/ml before ERT, fell to 18.9 pg/ml. In conclusion, plasma BNP levels may be useful for evaluating the effectiveness of ERT for heterozygous Fabry's disease, even in patients who demonstrate no improvement in echocardiographic parameters of cardiac structure and function.

Tissue Doppler echocardiography for predicting arterial stiffness assessed by cardio-ankle vascular index.

It has been reported that left ventricular (LV) diastolic functional parameters assessed by conventional Doppler echocardiography, which measures blood flow velocities in cardiac cavity, correlate with arterial stiffness assessed by the cardio-ankle vascular index (CAVI) and are markers for increased risk of cardiovascular events. Recently, tissue Doppler echocardiography, which measures velocities of regional cardiac wall, has been widely used for assessment of LV diastolic function because of more accuracy than conventional Doppler echocardiography. However, there are no data regarding the ability of tissue Doppler echocardiography for predicting increased arterial stiffness. We investigated the correlation of LV diastolic functional parameters from tissue Doppler echocardiography to CAVI in order to clarify the ability of tissue Doppler echocardiography for predicting increased arterial stiffness in patients with cardiovascular risk factors. Enrolled in the study were 70 patients (69 +/- 8 years) who had no overt heart disease, but had at least one of hypertension, diabetes, and dyslipidemia. The peak early diastolic mitral annular velocity (E') was measured as an index of LV diastolic function using tissue Doppler echocardiography. The E' was correlated with CAVI (r = -0.518, p < 0.001). The optimal cut-off point for the detection of abnormal CAVI (> or = 8.81) was 5.6 cm/s for E' (sensitivity 71%, specificity 71%). The decrease in E' correlated with both LV diastolic dysfunction and increased arterial stiffness. Therefore, the LV diastolic dysfunction assessed by tissue Doppler echocardiography may be useful for predicting increased arterial stiffness and cardiovascular events in the patients with risk factors.

Relationship between myocardial flow reserve by oxygen-15 water positron emission tomography in the subacute phase of myocardial infarction and left ventricular remodeling in the chronic phase.

The purposes of this study were to examine the effects of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) on myocardial flow reserve in patients with acute myocardial infarction (AMI) in the subacute phase using oxygen-15 positron emission tomography (PET) and to elucidate the relationship between the myocardial flow reserve and remodeling in the chronic phase. Sixty patients who had been treated with coronary angioplasty within 12 h after the onset of AMI were enrolled. Patients were divided into an enalapril (ACEI) group and a candesartan (ARB) group. The myocardial flow reserve was measured by oxygen-15 water PET in the subacute phase from the 20th to the 30th day after the onset of AMI. Left ventriculography was performed to measure the left ventricular ejection fraction in the chronic phase about 6 months after the onset. Ten patients (33%) in the enalapril group and 4 patients (13%) in the candesartan group stopped taking their respective medications within a few days of starting, because of side effects such as cough or hypotension. Thus, the prevalence of medication intolerance was higher in the enalapril group. The myocardial flow reserve in the subacute phase and the left ventricular ejection fraction in the chronic phase were lower in the enalapril group (2.08 +/- 0.30 and 42 +/- 6%) than in the candesartan group (2.25 +/- 0.20 and 49 +/- 5%) (p < 0.05). The myocardial flow reserve significantly correlated with the left ventricular ejection fraction in all patients (r = 0.45, p < 0.01). The myocardial flow reserve assessed by PET in the subacute phase after AMI was found to be related to left ventricular remodeling in the chronic phase.

A new index of "cardiac age" derived from echocardiography: influence of hypertension and comparison with pulse wave velocity.

Although pulse wave velocity is the primary indicator of arteriosclerosis and is widely used as an index of vascular age in anti-aging medicine, no index is available to quantify cardiac age. We proposed a "cardiac age" index and sought to clarify its clinical significance. The study subjects were 234 patients with atherosclerosis-related diseases. These patients were divided into 127 normotensive (mean age: 64+/-12 years) and 107 hypertensive (mean age: 65+/-11 years) patients. Echocardiography was performed, and brachial-ankle pulse wave velocity (baPWV) was measured using an automatic waveform analyzer. The index of cardiac age was determined as 1,000xVS(ot)/BSA/(VS-AO), where VSot (mm) was the ventricular septal thickness at the left ventricular outflow tract, BSA (m2) was the body surface area, and VS-AO (degree) was the angle between the basal ventricular septum and the ascending aorta. The index of cardiac aging correlated significantly with age in both the normotensive (r=0.63, p<0.001) and hypertensive (r=0.58, p<0.001) patients, and these correlations were closer than those between transmitral E/A (early to atrial velocity) ratio and age in normotensive (r=0.54, p<0.001) and hypertensive (r=0.44, p<0.001) patients. The slope between age (x-axis) and the index of cardiac age (y-axis) was greater in hypertensive (1.50) than normotensive (1.32) patients. Stepwise regression analysis showed that age (beta coefficient=0.35, p<0.001), the presence of hypertension (beta coefficient=0.26, p<0.001), the left ventricular mass index (beta coefficient=0.34, p<0.001), the left ventricular end-diastolic dimension (beta coefficient=-0.35, p<0.001), the dimension of the left atrium (beta coefficient=0.14, p=0.014), and the ratio of E to A (E/A) (beta coefficient=-0.12, p=0.046) were independently associated with the index of cardiac age. The index was also significantly correlated with baPWV (r=0.53, p<0.001). The proposed index of cardiac age can quantitatively assess cardiac morphological changes due to aging and/or hypertension and may be a useful marker of peripheral arterial stiffening.

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.

BACKGROUND: Cardioembolic 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 patient's clinical variables. METHODS: Our 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. RESULTS: Plasma 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 (Chi2 = 127.5, p < 0.001). CONCLUSION: It 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.

Relationship of cardiac hypertrophy and diastolic dysfunction assessed by echocardiography with atherosclerosis in retinal arteries in hypertensive patients.

Although left ventricular (LV) hypertrophy and diastolic dysfunction assessed by echocardiography are established risk markers of cardiovascular events in hypertensive patients, relationships between these echocardiographic findings and atherosclerosis have not been fully elucidated. The purpose of this study was to examine the relationships between atherosclerosis of the retinal arteries and echocardiographic findings in hypertensive patients. Forty hypertensive patients were divided into two groups according to Scheie's classification by ophthalmologists: 20 patients with stage 1 changes (visible broadening of the light reflex from the artery with minimal arteriovenous compression) and 20 patients with stage 2 changes (more prominent than those in stage 1). Standard echocardiography was performed to measure LV mass index for evaluating LV hypertrophy and conventional diastolic transmitral flow velocities for assessing LV diastolic function. Mitral annular velocities were also measured for evaluating LV diastolic function using tissue Doppler echocardiography. The LV mass index was larger in stage 2 (130 +/- 39 g/m(2)) than stage 1 (96 +/- 16 g/m(2)) patients (p = 0.001). Peak early diastolic mitral annular velocity (E') was lower in stage 2 (5.9 +/- 0.9 cm/s) than stage 1 (7.9 +/- 1.7 cm/s) patients (p = 0.001). The optimal cutoff points for the diagnosis of Scheie stage 2 were 6.6 cm/sec for E' (sensitivity 75%, specificity 85%) and 111 g/m(2) for LV mass index (sensitivity 70%, specificity 90%). In conclusion, in hypertensive patients, the extent of atherosclerosis in the retinal arteries can be estimated by LV hypertrophy and diastolic dysfunction assessed by echocardiography.

Differences in left ventricular hypertrophy and dysfunction between patients with cerebral hemorrhage and those with cerebral infarction.

Left ventricular (LV) hypertrophy and dysfunction due to hypertension have been established as risk markers for stroke in hypertensive patients. The purpose of this study was to examine the differences in LV hypertrophy and dysfunction between patients with cerebral hemorrhage and those with cerebral infarction. The study enrolled 23 hypertensive patients with cerebral infarction, 25 hypertensive patients with cerebral hemorrhage, and 24 normotensive controls (controls). Standard echocardiography was performed; LV mass index was measured to evaluate LV hypertrophy, and conventional diastolic transmitral flow velocities were measured to assess LV diastolic function, which was also evaluated by measuring mitral annular velocities using tissue Doppler echocardiography. The Tei index, which reflects both the diastolic and systolic function of LV, was also calculated. The LV mass index and Tei index were significantly higher in cerebral hemorrhage (116 +/- 38 g/m(2) and 0.57 +/- 0.13) than those in controls (92 +/- 20 g/m(2) and 0.46 +/- 0.10) (p < 0.05). In contrast, the LV mass index and Tei index in cerebral infarction (100 +/- 27 g/m(2) and 0.46 +/- 0.12) were not different from those in controls. Thus, the Tei index was significantly worse in the patients with cerebral hemorrhage than in those with cerebral infarction (p < 0.05). On the other hand, the parameters, which reflect diastolic function, showed no significant differences between cerebral hemorrhage and cerebral infarction. These results indicate that LV hypertrophy and dysfunction due to hypertension are more apparent in patients with cerebral hemorrhage than in those with cerebral infarction.

Cardiac diastolic dysfunction is associated with cerebral white matter lesions in elderly patients with risk factors for atherosclerosis.

Cerebral white matter lesions on magnetic resonance imaging (MRI) are considered to be the result of brain ischemic injury and a risk factor for clinical stroke. The purpose of this study was to elucidate the relationship between the cardiac diastolic function and cerebral white matter lesions in elderly patients with risk factors for atherosclerosis. The study subjects were 55 patients (75 +/- 7 years) with risk factors for atherosclerosis including hypertension, diabetes mellitus, and dyslipidemia. Patients with symptomatic cerebrovascular events were excluded from the study. Cerebral white matter lesions, which were defined as exhibiting high intensity regions on brain MRI, were evaluated with the degrees of periventricular hyperintensity (PVH) according to the Japanese Brain Dock Guidelines of 2003. Peak early diastolic mitral annular velocity (E' velocity) was measured by tissue Doppler echocardiography, and was used as a parameter of cardiac diastolic function. The mean value of E' velocity was decreased due to the cardiac diastolic dysfunction (5.2 +/- 1.4 cm/s). In addition, the E' velocity was inversely correlated with the degree of PVH (rho = -0.701, p < 0.001). Stepwise regression analysis showed that the decrease in the E' velocity (beta coefficient = -0.42, p < 0.001) and the presence of hypertension (beta coefficient = 0.31, p = 0.001) were independent determinants of the degree of PVH. Thus, cardiac diastolic dysfunction is correlated to the severity of cerebral white matter lesions, suggesting the cardio-cerebral connection in elderly patients with risk factors for atherosclerosis.

Efficacy and safety of rivaroxaban in extreme elderly patients with atrial fibrillation: Analysis of the Shikoku Rivaroxaban Registry Trial (SRRT).

BACKGROUND: The Shikoku Rivaroxaban Registry Trial (SRRT) is a retrospective survey of the use of rivaroxaban for stroke prevention in elderly patients in Shikoku, Japan. METHODS: The SRRT enrolled 1339 patients from 8 hospitals. Patients were divided into two groups according to their age, the extreme elderly group (453 patients aged ≧80 years) and the control group (886 patients aged <80 years). RESULTS: In the extreme elderly group, 41.5% of the patients had low body weight (<50kg) and 65.1% had abnormal renal function (creatinine clearance <50ml/min). The mean CHADS2, CHA2DS2-VASc, and HAS BLED scores were 2.7, 4.4, and 2.3, respectively. There were 333 (73.5%) patients who met the dosing criteria, and of these patients, 81.2% received rivaroxaban 10mg daily. Thromboembolic events occurred in 4 patients (0.94%/person year) and intracranial hemorrhage occurred in 4 patients (0.89%/person year). The incidence of these events was not significantly different from the control group. In addition, all patients with cerebral infarction had been treated with a smaller dose of rivaroxaban than recommended by the dosing criteria, suggesting that dosing criteria should be adhered to. CONCLUSION: These results suggest that rivaroxaban is effective and safe in extreme elderly patients with atrial fibrillation.

Granulocyte colony-stimulating factor facilitates the angiogenesis induced by ultrasonic microbubble destruction.

Ultrasonic destruction of microbubbles (US/MB) in the microcirculation causes local inflammatory cell infiltration, which has been shown to induce angiogenesis. Granulocyte colony-stimulating factor (G-CSF), which mobilizes myelomonocytic cells from the bone marrow and enhances vascular endothelial growth factor (VEGF) release from these cells, has also been applied to therapeutic angiogenesis induction. In the present study, we sought to examine the potential of G-CSF pretreatment to enhance the angiogenic effect of US/MB. Ischemic hindlimbs in mice were treated with either a predetermined minimal effective dose (300 mug/kg) of G-CSF, US/MB alone or G-CSF pretreatment followed by US/MB at seven days after removal of the femoral artery. Ultrasonic destruction of microbubbles was performed as intermittent pulsed local insonation using a diagnostic ultrasound scanner at a peak negative pressure of 1.4 MPa after intravenous injection of perfluorocarbon microbubbles. At 21 days after the treatment, we quantified the surface vascularity using a grid method and the capillary density using an alkaline phosphatase stain. Relative to the capillary density in normal muscle, the capillary density in the treated limbs was restored to 74 +/- 13% by G-CSF alone and 90 +/- 20% by US/MB alone (p < 0.05 vs. both untreated and G-CSF alone), and further increased to 101 +/- 21% by G-CSF pretreatment. The collateral growth induced by the combination of G-CSF pretreatment and US/MB was 2.8- and 1.4-fold greater than the growth induced by G-CSF alone and US/MB alone, respectively (p < 0.05 for both). Thus, pretreatment with a single minimal effective dose of G-CSF can augment the angiogenic effect of US/MB.

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.

Latent abnormal fatty acid metabolism in apparently normal perfusion during stress in patients with restenosis after coronary angioplasty: assessment by exercise stress thallium-201 and iodine-123-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid-dual myocardial single-photon emission computed tomography.

Restenosis is a major problem in patients undergoing coronary angioplasty. Reduced uptake of iodine-123-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (I-BMIPP-123) relatively to thallium-201 (Tl-201) has been attributed to the metabolic damage in the myocardium in patients with coronary artery disease. Therefore, we performed exercise stress Tl-201 and I-BMIPP-123 dual myocardial single-photon emission computed tomography (SPECT) to detect coronary restenosis in 48 patients (35 men and 13 women, mean age 66 +/- 8 years), followed by coronary angiography at follow-up. Patients were divided into 2 groups: those with (n = 24) and without (n = 24) restenosis. Redistribution of Tl-201 was seen more frequently in the restenosis group than in no-restenosis group (58% [14 of 24] vs 8% [2 of 24], p <0.05). Five of 10 patients (50%) with restenosis but without Tl-201 redistribution had Tl-201/I-BMIPP-123 discrepancy during stress. In patients without restenosis, only 1 patient had this discrepancy during stress. Incorporation of Tl-201/I-BMIPP-123 uptake discrepancy during stress significantly improved the sensitivity (58% [14 of 24] to 79% [19 of 24]) with preserved specificity (92% [22 of 24] to 88% [21 of 24]). Exercise stress Tl-201 and I-BMIPP-123 dual myocardial SPECT revealed that latent abnormal fatty acid metabolism may exist in apparently normal perfusion during stress in patients with restenosis after coronary angioplasty. Use of I-BMIPP-123 together with Tl-201 during stress SPECT substantially improved the diagnostic accuracy of restenosis based on Tl-201 redistribution (from 75% to 83%).

Usefulness of brain natriuretic peptide as a marker for separating cardiac and noncardiac causes of syncope.

We retrospectively evaluated the feasibility of measuring brain natriuretic peptide to identify cardiac syncope in 148 consecutive patients with syncope. Sixty-one patients with cardiac syncope were identified. A cut-off value of 40 pg/ml was used to determine the cardiac causes of syncope; the sensitivity and specificity for identification of cardiac syncope were 82% and 92%, respectively. Thus, measurement of brain natriuretic peptide concentrations may help confirm cardiac causes of syncope, and merits consideration for incorporation into the algorithm used to diagnose syncope.

Inhibition of migration and proliferation of rat vascular smooth muscle cells by a new HMG-CoA reductase inhibitor, pitavastatin.

The migration and proliferation of vascular smooth muscle cells (SMCs) are known to play roles in the pathogenesis of atherosclerosis. Therapy with a reductase inhibitor of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) ("statin") produces significant alterations in various SMC functions. The objectives of the present study were to determine whether pitavastatin, a new chemically synthesized and powerful statin, can affect angiotensin II (Ang II)- and platelet-derived growth factor (PDGF)-induced migration and proliferation of cultured rat vascular SMCs. The effect of pitavastatin on cell viability was also examined in these cells. Migration was evaluated by the Boyden's chamber method using microchemotaxis chambers. As expected, Ang II and PDGF BB potently stimulated cell migration in a concentration-dependent manner. Pitavastatin significantly inhibited Ang II (10(-6) mol/l)-induced migration at the concentrations of 10(-8) and 10(-7) mol/l. Pitavastatin also inhibited PDGF BB (1 ng/ml)-induced migration at concentrations between 10(-9) and 10(-8) mol/l in a relatively concentration-dependent manner. This statin modestly but significantly inhibited Ang II (10(-6) mol/l)- and PDGF BB (1 ng/ml)-induced DNA synthesis at concentrations between 10(-9) and 10(-7) mol/l. In addition, pitavastatin clearly inhibited Ang II (10(-6) mol/l)- and PDGF BB (1 ng/ml)-induced increases of cell number at concentrations between 10(-9) and 10(-7) mol/l. Pitavastatin did not affect lactate dehydrogenase release from these cells at the concentrations used in this experiment. In a trypan blue exclusion test, dead cells stained with trypan blue were not found 24 h after treatment with 10(-9), 10(-8) or 10(-7) mol/l of pitavastatin. These findings suggest that pitavastatin suppresses the migration and proliferation stimulated by Ang II and PDGF BB without affecting cell viability. Pitavastatin may exert an anti-atherogenic effect, in part, through these mechanisms.

Assessment of myocardial viability in prior myocardial infarction by intravenous bolus microbubble injection: a new time domain index to estimate regional relative myocardial blood volume.

We tested whether the duration of myocardial opacification by harmonic power Doppler imaging after intravenous bolus microbubble injection (with a definition of "the end of opacification") would reflect the remaining vascular bed in infarcted segments. In 28 patients with previous myocardial infarction and 20 control patients, we performed harmonic power Doppler imaging after intravenous bolus injection of 1.5 g of Levovist. Using multiframe trigger mode in which 4 consecutive frames were imaged at every sixth end systole, which formed 1 "burst," we recorded anterior/septal and inferior/posterior walls separately on the center of each apical view with individual boluses. The duration of segmental opacification was measured as the number of "bursts" in which color signals persisted until the fourth frame. The duration was similar between the anterior/septal and inferior/posterior walls (13 +/- 3 vs 13 +/- 3 bursts, not significant) in the control group. In myocardial infarction patients, the duration was significantly shorter in the infarcted than in the control segments (6 +/- 6 vs 14 +/- 3 bursts, P < .001) and their ratio and difference exhibited significant correlations (r = 0.82, P < .001 and r = 0.91, P < .001, respectively) with the activity ratio on thallium Tl 201 single-photon emission computed tomography at rest. Thus, the duration of opacification by harmonic power Doppler imaging after intravenous bolus microbubble injection, the measurement of which was standardized by using multiframe trigger mode, may be useful in assessing regional myocardial viability in patients with previous myocardial infarction.

Myocardial blood flow measurements in rats with simple pulsing contrast echocardiography.

Relationship between contrast intensity and ultrasound (US) pulsing interval has been utilized to quantify myocardial blood flow (MBF) during myocardial contrast echocardiography (MCE). We tested if an MCE method employing a simple pulsing sequence during intravenous contrast infusion has the ability to quantify MBF in rats. We performed MCE in 17 rats using a 5- to 12-MHz broadband transducer during microbubble infusion via the femoral vein. Acoustic density (AD) from the anterior wall of the left ventricle imaged in the short axis plane was plotted against the frame number after shortening the pulsing interval (PI) from 1:20 to 1:1 end-systolic ECG gating. The relation between AD and frame number was fitted to a decay function. The rate of the AD decay was decreased during dipyridamole infusion, but was increased by causing coronary stenosis. The AD during long PI imaging remained unchanged during the interventions. Estimated MBF by MCE after correction by heart rate exhibited a close correlation (r = 0.83) with the present "gold standard" of colored microsphere-derived MBF. Thus, the decay rate of the contrast intensity obtained with the high-frequency transducer after abrupt shortening of PI during intravenous microbubble infusion may provide for noninvasive measurement of MBF in rats.