Soluble urokinase-type plasminogen activator receptor represents exercise tolerance and predicts adverse cardiac events in patients with heart failure.

Soluble urokinase-type plasminogen activator receptor (suPAR) is a membrane-binding protein that is released into the blood stream by immune activation. Recent reports suggest that circulating suPAR levels are associated with adverse cardiovascular outcomes. Exercise tolerance is an independent predictor of prognosis in patients with heart failure (HF); however, the relationship between serum suPAR level and exercise tolerance is unclear. We prospectively enrolled 94 patients who were hospitalized for worsening of HF. All patients underwent a symptom-limited cardiopulmonary exercise test to evaluate exercise tolerance. The median value of serum suPAR was 4848 pg/ml. During follow up, 44 patients (47%) were admitted for all-cause mortality and re-hospitalization for HF. Median serum suPAR was significantly higher in the patients with cardiac events than in the patients with non-event group. Patients were divided into two groups according to circulating suPAR levels. Kaplan-Meier analysis demonstrated that adverse cardiac events were significantly higher in the high suPAR group (log-rank p = 0.023). Multivariate analysis revealed that suPAR was independently correlated with the parameters of exercise tolerance such as anaerobic threshold (p = 0.007) and peak oxygen uptake (p = 0.005). suPAR levels predicted adverse cardiac events and independently correlated with the parameters of exercise tolerance. suPAR could be a useful surrogate biomarker of exercise tolerance in patients with HF.

Serum brain-derived neurotrophic factor level and exercise tolerance complement each other in predicting the prognosis of patients with heart failure.

Brain-derived neurotropic factor (BDNF) is a myokine that plays a key role in regulating survival, growth, and maintenance of neurons. We investigated whether the serum BDNF level at discharge could predict the prognosis in patients with heart failure (HF). Furthermore, we aimed to examine the relationship between this myokine and exercise tolerance. We prospectively enrolled 94 patients who were hospitalized for worsening HF and had cardiac rehabilitation. At discharge, the serum BDNF level of all patients was measured using a commercial ELISA kit and they underwent a cardiopulmonary exercise test to measure peak oxygen uptake (peak VO2). Correlation was not observed between BDNF and peak VO2. Kaplan-Meier analysis demonstrated that cardiac death or rehospitalization owing to worsening HF was significantly higher in the low BDNF group (p = 0.023). The combination of peak VO2 and BDNF levels led to the identification of subgroups with significantly different probabilities of events (p = 0.005). In particular, in the low BDNF and low peak VO2 group, the frequency of rehospitalization within half a year after discharge was much higher than that in other groups. Multivariate analysis found BDNF as an independent factor of adverse events (hazard ratio 0.956; 95% confidence interval 0.911-0.999; p = 0.046). The serum BDNF level at discharge may be a useful biomarker of the prognosis in patients with HF. Furthermore, combining BDNF and peak VO2 may be useful for predicting early cardiac events.

Administration of tolvaptan with reduction of loop diuretics ameliorates congestion with improving renal dysfunction in patients with congestive heart failure and renal dysfunction.

In patients with congestive heart failure and renal dysfunction, high dose of diuretics are necessary to improve congestion, which may progress to renal dysfunction. We examined the efficacy of tolvaptan with reduction of loop diuretics to improve renal function in patients with congestive heart failure and renal dysfunction. We conducted a multicenter, prospective, randomized study in 44 patients with congestive heart failure and renal dysfunction (serum creatinine concentration ≥1.1 mg/dl) treated with conventional diuretics. Patients were randomly divided into two groups: tolvaptan (15 mg) with a fixed dose of diuretics or with reducing to a half-dose of diuretics for 7-14 consecutive days. We examined the change of urine volume, body weight, serum creatinine and electrolyte concentrations in each group. Both groups demonstrated significant urine volume increase (724 ± 176 ml/day in the fixed-dose group and 736 ± 114 ml/day in the half-dose group) and body weight reduction (1.6 ± 1.5 kg and 1.6 ± 1.9 kg, respectively) from baseline, with no differences between the two groups. Serum creatinine concentration was significantly increased in the fixed-dose group (from 1.60 ± 0.47 to 1.74 ± 0.66 mg/dl, p = 0.03) and decreased in the half-dose group (from 1.98 ± 0.91 to 1.91 ± 0.97 mg/dl, p = 0.10). So the mean changes in serum creatinine concentration from baseline significantly differed between the two groups (0.14 ± 0.08 mg/dl in the fixed-dose group and -0.07 ± 0.19 mg/dl in the half-dose group, p = 0.006). The administration of tolvaptan with reduction of loop diuretics was clinically effective to ameliorate congestion with improving renal function in patients with congestive heart failure and renal dysfunction.

Safety and efficacy of high-rate cutoff and long detection interval ICD programming in secondary prevention patients.

Several trials demonstrated that a long detection interval and a high-rate cutoff reduced implantable cardioverter-defibrillator (ICD) therapy in primary prevention patients. However, only a few data are available for secondary prevention (SP) patients. The aim of this study was to evaluate whether these ICD programming would be effective in reducing ICD therapies in SP patients. We enrolled 65 SP patients under ICD or cardiac resynchronization therapy with the defibrillator programmed with the same setting (conventional setting). During follow-up, we changed detection rates in each zone; cycle length (CL) ≤400 to ≤370 ms for ventricular tachycardia (VT) zone, CL ≤350 to ≤320 ms for fast VT zone, CL ≤300 to ≤270 ms for ventricular fibrillation (VF) zone, and number of intervals to detect ventricular tachyarrhythmia in VF zone: 12-24. We retrospectively compared the incidences of ICD therapies, syncope, and hospitalization due to slow VT under the detection rate between both settings. Median follow-up periods were 5.0 (interquartile range 2.5-7.8) and 2.5 years (interquartile range 2.3-2.7) in conventional and strategic settings, respectively. The incidence of appropriate ATP and shock significantly decreased in strategic setting (conventional and strategic settings: 21.2 and 4.8 ATPs per year, respectively, OR 0.18, 95 % CI 0.06-0.54, p = 0.002, 26.1 and 7.8 shocks per year, respectively, OR 0.29, 95 % CI 0.09-0.88, p = 0.03). The incidence of overall inappropriate therapy significantly decreased (conventional and strategic settings: 17.6 and 2.8 therapies per year, respectively, OR 0.14, 95 % CI 0.05-0.44, p = 0.01). The incidence of syncope and slow VT was not significantly different between both settings. In conclusion, ICD programming-combined long detection interval with high-rate cutoff was effective in reducing appropriate shock and inappropriate therapy without increasing the incidence of syncope and slow VT in SP patients.

Utility of T-wave alternans during night time as a predictor for ventricular fibrillation in patients with Brugada syndrome.

The prognostic value of T-wave alternans (TWA) during the night time in patients with Brugada syndrome (Br-S) remains unknown. We assessed TWA for risk stratification using 24-h multichannel Holter electrocardiogram (24-M-ECG) in Br-S. We enrolled 129 patients with Br-S [grouped according to histories of ventricular fibrillation (VF), n = 16; syncope, n = 10; or no symptoms (asymptomatic), n = 103] and 11 controls. Precordial electrodes were attached to the third (3L-V1, 3L-V2) and fourth (4L-V1, 4L-V2 and 4L-V5) intercostal spaces. We measured the values of maximum TWA (max-TWA) during the night time (12 a.m.-6 a.m.) and the day time (12 p.m.-6 p.m.) and calculated parameters of heart rate variability. Compared to the asymptomatic and control groups, the VF and syncope groups showed significantly greater 3L-V2 max-TWA during the night time. The cutoff value for the 3L-V2 max-TWA during the night time was determined as 20 µV (sensitivity 94 % and specificity 48 %; p = 0.01). Multivariate analysis revealed that 3L-V2 max-TWA during the night time ≥20 µV and previous VF episodes were independent predictors of future VF episodes. During a mean follow-up period of 68 ± 37 months, 16 patients experienced VF episodes. The incidence of VF episodes was the highest during the night time (p < 0.001). The 3L-V2 max-TWA during the night time may be a useful predictor for VF episodes in patients with Br-S.

Effects of Night Shift Work on Nighttime Blood Pressure among Healthy Young Female Medical Workers.

Background Although night shift is an independent risk factor of cardiovascular disease (CVD), the underlying mechanisms have not been understood. Nocturnal blood pressure (BP) and increased BP variability are associated with CVD. However, little is known regarding the impact of night shift on nocturnal BP variables. Methods The study population consisted of 30 healthy female medical shift workers (mean age, 28±6 years) with flexible blood vessels (mean cardio-ankle vascular index, 5.8±0.9). Nocturnal BP variables were measured after day and night shifts using a home BP monitoring device. Similarly, sleep status (total sleep time, sleep efficiency, and snoring) were measured using a noncontact radiofrequency sensor. Results Nocturnal diastolic BP variability (7.0±5.3 mm Hg vs 4.7±2.7 mm Hg; p<0.01) was significantly higher after night shift than after day shift, whereas no significant differences in systolic BP variables, mean diastolic BP, and sleep status were observed. Conclusions Among young healthy women with flexible blood vessels, night shift increased nighttime diastolic BP variability, rather than systolic BP variables independent of sleep disorder. These findings imply that increased nighttime diastolic BP variability derived from night shift might stimulate an early- stage atherosclerotic process that predisposes patients to future CVD.

Rationale and Design of the Double-Blind, Randomized, Placebo-Controlled Multicenter Trial on Efficacy of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure (EARLIER).

BACKGROUND AND AIMS: Aldosterone is one of the major factors to cause organ damage during an acute phase of heart failure (HF), and many reports have demonstrated that patients with acute decompensated HF (ADHF) have high blood aldosterone concentrations, and the high aldosterone concentrations predict poor prognosis in patients with HF. These findings suggest that eplerenone, an antagonist of aldosterone receptors may provide a new concept and strategy for the treatment of ADHF, protecting the heart and other organs during chronic phases, depending on the restoration of hemodynamic abnormalities. METHODS: EARLIER is an event-driven clinical trial with an estimated enrolment of 300 patients hospitalized with ADHF with reduced left ventricular ejection fraction. ADHF includes ischemic or non-ischemic HF, and patients can be enrolled within 72 h after the visit to the hospital. We randomize the patients taking standard therapies for ADHF to the eplerenone and placebo groups. Eplerenone, either 25 or 50 mg, is administered for 6 months in the eplerenone group, and the corresponding placebo is administered in the placebo group on top of the standard care. We set the primary endpoint as the incidence of the composite endpoint (cardiac death or first re-hospitalization due to cardiac disease) 6 months after the enrollment, and also check the quality of life, i.e., exercise capacity and safety features of eplerenone. CONCLUSION AND PERSPECTIVES: EARLIER is a clinical trial of eplerenone targeting ADHF and also the first multicenter investigator-initiated phase III trial in the cardiovascular field in Japan, funded by the Japanese government.

Tolvaptan attenuates left ventricular fibrosis after acute myocardial infarction in rats.

Tolvaptan, a non-peptide V2-receptor antagonist, is a newly developed diuretic agent. Recently, we reported that tolvaptan has diuretic as well as anti-inflammatory and anti-fibrotic actions in chronic heart failure. In this study, we investigated whether tolvaptan has a cardioprotective effect in acute heart failure after myocardial infarction (MI). After MI induction, rats were randomized into 6 groups as follows: vehicle group, group treated with 15 mg∙kg⁻¹âˆ™day⁻¹ furosemide, 2 groups treated with 3 or 10 mg∙kg⁻¹âˆ™day⁻¹ tolvaptan, and 2 groups treated with 15 mg∙kg⁻¹âˆ™day⁻¹ furosemide combined with 3 or 10 mg∙kg⁻¹âˆ™day⁻¹ tolvaptan. Each agent was administered for 2 weeks, and blood pressure levels and infarct sizes were similar in all MI groups. Lower left ventricular end-systolic volumes and greater improvement of left ventricular ejection fraction were observed in the tolvaptan-treated groups compared with the vehicle group. In contrast, furosemide alone did not improve them. Sirius red staining revealed that tolvaptan significantly repressed MI-induced interstitial fibrosis in the left ventricle. MI-induced mRNA expressions related to cardiac load, inflammation, and fibrosis were significantly attenuated in the combination group. The combination treatment also repressed MI-induced mineralocorticoid receptor expression. Tolvaptan, or combination of furosemide and tolvaptan, may improve cardiac function in acute MI.

Effects of intravenous atrial natriuretic peptide and nitroglycerin on coronary vasodilation and flow velocity determined using 3 T magnetic resonance imaging in patients with nonischemic heart failure.

Although atrial natriuretic peptide (ANP) is widely used in patients with congestive heart failure (CHF), little is known about its effect on epicardial coronary arteries. Magnetic resonance imaging (MRI) enables precise measurement of coronary vasodilation and flow velocity. In this study, we examined the changes in epicardial coronary artery size and flow velocity in response to intravenous infusion of ANP or nitroglycerin (NTG) by using 3 T MRI in patients with CHF. The study cohort contained a total of 14 subjects: 8 patients with CHF and 6 healthy volunteers as controls, randomly divided into two groups: the ANP group (0.03 µg/kg/min) and the NTG group (0.3 µg/kg/min). Cross-sectional MR angiography and phase-contrast flow velocity of the right coronary artery in the same in-plane slice were obtained at the baseline, during drug infusion, and at two subsequent time points after stopping drug infusion. A significant increase was observed in the coronary cross-sectional area at 15 min after drug infusion in both groups compared with that at baseline; however, a late peak was observed at 15 min after stopping infusion in the ANP group. No significant differences were detected in the flow velocity in both groups. Furthermore, although NTG increased the heart rate, this change was not found in the ANP group. Coronary vasodilation and flow velocity can be measured simultaneously using 3 T MRI. Using this method, we showed that the effects of ANP on the coronary artery vasodilation and flow velocity were not inferior to those of NTG, with no significant alteration in heart rate.

Diagnostic accuracy of transthoracic and transesophageal echocardiography for the diagnosis of bicuspid aortic valve: comparison with operative findings.

BACKGROUND: Bicuspid aortic valve (BAV) is associated with an increased risk of aortic valve (AV) dysfunction, aortic dissection, and infective endocarditis. Therefore, its accurate diagnosis is critical. The morphological features of AVs are generally evaluated by transthoracic echocardiography (TTE) or transesophageal echocardiography (TEE), however, the difference in the diagnostic capability of these imaging modalities for detecting BAV remains unclear. Here, we compared these 2 methods to determine their accuracy, and to clarify each role in the diagnosis of BAV. METHODS: This blind study evaluated 126 patients (age, 70.3 +/- 7.8 years) who subsequently underwent AV replacement. The number of AV cusps of each patient was estimated by TTE and TEE and compared to the number of AV written in the operative record. Patients with poor echocardiographic images were not excluded. RESULTS: Surgical findings showed 97 tricuspid AVs and 29 BAVs. The sensitivity, specificity, and accuracy for the diagnosis of BAV were 61%, 81%, and 77%, respectively, for TTE and 86%, 90%, and 89%, respectively, for TEE. The accuracy of TEE was significantly higher than that of TTE (p = 0.016). In non-calcified AVs, the accuracy of TTE was similar to that of TEE (96%, each) whereas in calcified AVs, TTE had a lower accuracy than TEE (72% vs 87%, p = 0.011). The feasibility was significantly higher for TEE than for TTE (98% vs 90%, p = 0.003). CONCLUSIONS: TEE provides higher accuracy and feasibility than TTE in the diagnosis of BAV, and it should therefore be indicated when morphological features of AVs cannot be evaluated by TTE.

Novel device that produces carbon dioxide mist for myocardial infarction treatment in rats.

BACKGROUND: Carbon dioxide (CO(2)) baths have been used to treat a variety of diseases, but developing an artificial bath of highly concentrated CO(2) is difficult. Here, we tried the efficacy of a novel device instead of a CO(2) bath. METHODS AND RESULTS: Using a device equipped with double fluid nozzles, CO(2) gas and H(2)O were compounded and compressed at 4 barometric pressures. As a result, CO(2) gas was dissolved in H(2)O, which contained a few micrometers of CO(2) particles, namely, a CO(2) mist. Wistar rats with myocardial infarction (MI) by ligation of the left coronary artery were percutaneously administered CO(2) mist or CO(2) gas alone or no treatment for 30 min daily. With regard to tissue blood flow during treatment, the group treated with CO(2) mist had significantly increased tissue oxygenated hemoglobin levels and tissue saturation levels, and significantly decreased deoxygenated hemoglobin levels compared with the group treated with CO(2) gas. After 4 weeks treatment, the group treated with CO(2) mist had a significantly improved ejection fraction by echocardiography compared with the untreated group. Interestingly, the group treated with CO(2) mist had significantly increased nitrate concentrations in serum and vascular endothelial growth factor mRNA expression levels in the myocardium compared with the untreated group. CONCLUSIONS: Our new mist production device may be potentially useful for the treatment of heart failure caused by MI.

Detailed observation of arterial healing after stent implantation in swine arteries by using optical coherence tomography.

BACKGROUND: Histopathological examination is not suitable for sequential in vivo analysis of arterial healing after stenting because it can be performed only after the animals are killed. Optical coherence tomography (OCT) provides higher resolution than intravascular ultrasound (IVUS). The aim of this study was to compare arterial healing images after stenting on the basis of the findings of histopathological examination, IVUS, and OCT. METHODS: We examined 12 vessels; 12 bare-metal stents were implanted in 6 miniature swine. Histopathological examination, IVUS, and OCT imaging were performed at 1 and 4 weeks after stenting. For quantitative analysis of IVUS and OCT images, we examined cross-sectional frames at 1-mm intervals. For neointimal coverage analysis, the neointimal coverage score was classified into 1 of the 4 categories. A fully covered strut was scored as 3, a partially covered strut was scored as 1 or 2, and an uncovered strut was scored as 0. RESULTS: In IVUS and OCT analyses, the average neointimal thickness increased between 1 and 4 weeks (p < 0.0001). OCT revealed higher scores at 1 and 4 weeks than IVUS did (at week 1, p < 0.0001; at week 4, p < 0.0001). OCT analysis evaluated the neointimal coverage similarly to histopathological examination. CONCLUSIONS: On assessment of arterial healing after stenting, we found that the results of the histological examination were more similar to those of the OCT analysis than to those of the IVUS. An OCT imaging device can be used to precisely and sequentially analyze the arterial healing process after stenting.

Efficacy and Safety of Early Initiation of Eplerenone Treatment in Patients with Acute Heart Failure (EARLIER trial): a multicentre, randomized, double-blind, placebo-controlled trial.

AIMS: A mineralocorticoid receptor antagonist (MRA) is effective in patients with chronic heart failure; however, the effects of the early initiation of an MRA in patients with acute heart failure (AHF) have not been elucidated. METHODS AND RESULTS: In this multicentre, randomized, double-blind, placebo-controlled, parallel-group study, we focused on the safety and effectiveness of the treatment with eplerenone, a selective MRA in 300 patients with AHF, that is, 149 in the eplerenone group and 151 in the placebo group in 27 Japanese institutions. The key inclusion criteria were (i) patients aged 20 years or older and (ii) those with left ventricular ejection fraction of ≤40%. The primary outcome was a composite of cardiac death or first re-hospitalization due to cardiovascular disease within 6 months. The mean age of the participants was 66.8 years, 27.3% were women, and the median levels of brain natriuretic peptide were 376.0 pg/mL. The incidences of the primary outcome were 19.5% in the eplerenone group and 17.2% in the placebo group [hazard ratio (HR): 1.09, 95% confidence interval (CI): 0.642-1.855]. In prespecified secondary outcomes, HR for the composite endpoint, cardiovascular death, or first re-hospitalization due to heart failure within 6 months was 0.55 (95% CI: 0.213-1.434). The safety profile for eplerenone was as expected. CONCLUSION: The early initiation of eplerenone in patients with AHF could safely be utilized. The reduction of the incidence of a composite of cardiovascular death or first re-hospitalization for cardiovascular diseases by eplerenone is inconclusive because of inadequate power.

Increased oxidative stress during exercise predicts poor prognosis in patients with acute decompensated heart failure.

AIMS: Oxidative stress plays an important role in the development and progression of heart failure (HF). Although exercise and oxidative stress are closely related, the effect of acute exercise on reactive oxygen species production and the fluctuation on prognosis are unclear. METHODS AND RESULTS: We enrolled 94 patients who were hospitalized for worsening HF (mean age 68.0 ± 14.5 years old, 63.8% male). The changes in diacron-reactive oxygen metabolites (d-ROM) values, a marker of oxidative stress, before and after a cardiopulmonary exercise test were considered as Δd-ROM. The mean follow-up period was 24 ± 13 months, during which 15 patients had all-cause death or left ventricular assist system implantation. Kaplan-Meier analysis demonstrated that all-cause death or left ventricular assist system implantation was significantly higher in the Δd-ROM-positive group than in the Δd-ROM-negative group (log-rank P = 0.047). Elevated Δd-ROM levels were associated with increased mortality risk. Multivariate analysis adjusted for body mass index and peak oxygen uptake revealed that Δd-ROM was an independent prognostic factor of adverse events (Tertile 3 vs. 1; hazard ratio: 4.57; 95% confidence interval: 1.21-29.77; P = 0.022). CONCLUSIONS: Patients with HF who underwent a cardiopulmonary exercise test and had an increased oxidative stress marker level had a poor prognosis. The appropriate exercise intensity could be determined by evaluating the changes in oxidative stress status in response to acute exercise in patients with HF.

Greater nighttime blood pressure variability is associated with left atrial enlargement in atrial fibrillation patients with preserved ejection fraction.

Left atrial enlargement is an independent risk factor for ischemic stroke in patients with atrial fibrillation. Little is known regarding the association between nighttime blood pressure variability and left atrial enlargement in patients with atrial fibrillation and preserved ejection fraction. The study population consisted of 140 consecutive patients with atrial fibrillation (mean age 64 ± 10 years) with preserved ejection fraction (≥50%). Nighttime blood pressure was measured at hourly intervals, using a home blood pressure monitoring device. Nighttime blood pressure variability was expressed as the standard deviation of all readings. Left atrial volume index was measured using the modified Simpson's biplane method with transthoracic echocardiography. Multiple regression analysis indicated that nighttime mean systolic/diastolic blood pressure and its variability remained independently associated with left atrial enlargement after adjustment for age, sex, anti-hypertensive medication class, and left ventricular mass index (P < 0.01). When patients were divided into four groups according to nighttime blood pressure and its variability, the group with higher nighttime blood pressure and its variability had significantly larger left atrial volume than the group with lower nighttime blood pressure and its variability (46.6 ml/m2 vs. 35.0 ml/m2, P < 0.0001). Higher nighttime blood pressure and its variability are associated with left atrial enlargement. The combination of nighttime blood pressure and its variability has additional predictive value for left atrial enlargement. Intensive intervention for these high-risk patients may avoid or delay progression of left atrial enlargement and reduce the risk of stroke.

Right ventricular enlargement predicts responsiveness to tolvaptan in congestive heart failure patients with reduced ejection fraction.

BACKGROUND: Tolvaptan is a vasopressin type 2 receptor antagonist used in heart failure (HF) with refractory diuretic resistance. However, since tolvaptan is also ineffective in some HF patients with reduced ejection fraction (HFrEF), the identification of responders is important. METHODS: The study population consisted of 51 HFrEF patients who were administered tolvaptan (EF, 28 ±â€¯7%). We defined responders as patients with a ≥50% increase in urine volume during the 24-hours after administration of tolvaptan. All patients underwent comprehensive transthoracic echocardiography before administration of tolvaptan. Patients were followed for 120 days to ascertain secondary events (cardiac death and rehospitalization for HF). RESULTS: Multiple regression analysis indicated that right ventricular (RV) enlargement (defined as basal RV diameter > 41 mm and midlevel RV diameter > 35 mm, according to guidelines) remained a predictor of response after adjustment for age, sex, starting dosage of tolvaptan, and estimated glomerular filtration rate (odds ratio, 4.88; 95%-confidence interval, 1.26-18.9; P < 0.05), whereas left ventricular parameters and RV dysfunction were not. Kaplan-Meier curves indicated responsiveness to tolvaptan was associated with better prognosis among the overall population (P < 0.05); similar trends were observed among patients with RV dilatation (P = 0.056). CONCLUSIONS: These findings suggest that RV enlargement, which represents right-sided volume overload, elevated filling pressure, and diastolic dysfunction similar to that seen in constrictive pericarditis, predicts responsiveness to tolvaptan in patients with HFrEF. Moreover, administration of tolvaptan may have the potential to improve the reportedly poor prognosis for HFrEF patients with RV dilatation.

A novel application of myocardial contrast echocardiography to evaluate angiogenesis by autologous bone marrow cell transplantation in chronic ischemic pig model.

OBJECTIVES: We investigated the feasibility of myocardial contrast echocardiography (MCE) to evaluate regional perfusion after bone marrow cell transplantation. BACKGROUND: The myocardial microvessels improved by cell transplantation are too small to visualize with conventional angiography. METHODS: Fourteen mini-pigs from the Nippon Institute for Biological Science were used. The proximal left anterior descending coronary artery was ligated. One month later, nine pigs survived. Six pigs received autologous cell transplantation into the left ventricular anterior wall: bone marrow mononuclear cells (BMMNCs) (n = 3) and bone marrow stromal cells (BMSCs) (n = 3). The other three pigs received saline (control group, n = 3). The pigs were sacrificed one month later. Myocardial contrast intensity (MCI) with a contrast agent was measured using the SONOS 5500 system (Philips). Capillary density (CD) and MCI were measured at four areas: anteroseptum (nontransplanted infarct area), anterior wall (transplanted infarct area), septum (border zone), and lateral wall (normal). We compared the anteroseptum with the anterior wall by MCI and CD. RESULTS: In the BMMNC and BMSC subsets, the CD of the anterior wall was higher than that of the anteroseptum (p < 0.001). There was a linear relation between MCI and CD (acoustic unit [AU2] = 0.234 CD + 0.010, r = 0.92, p < 0.001). At one month after cell transplantation, MCI of the anterior wall increased in the BMMNC and BMSC subsets (p < 0.05), although it did not change in the control group. The ratio of wall thickness (systole/diastole) in the transplanted infarct area was larger than that in the nontransplanted infarct area (p < 0.01). CONCLUSIONS: Myocardial contrast echocardiography is useful to evaluate regional perfusion, which was enhanced by bone marrow cell transplantation.

Aortic arch atherosclerosis in patients with severe aortic stenosis can be argued by greater day-by-day blood pressure variability.

BACKGROUND AND PURPOSE: Although it is well known that the prevalence of aortic arch plaques, one of the risk factors for ischemic stroke, is high in patients with severe aortic stenosis, the underlying mechanisms are not well understood. Increased day-by-day blood pressure (BP) variability is also known to be associated with stroke; however, little is known on the association between day-by-bay BP variability and aortic arch atherosclerosis in patients with aortic stenosis. Our objective was to clarify the association between day-by-day BP variables (average values and variability) and aortic arch atherosclerosis in patients with severe aortic stenosis. METHODS: The study population consisted of 104 consecutive patients (mean age 75 ± 8 years) with severe aortic stenosis who were scheduled for aortic valve replacement. BP was measured in the morning in at least 4 consecutive days (mean 6.8 days) prior to the day of surgery. Large (≥4 mm), ulcerated, or mobile plaques were defined as complex plaques using transesophageal echocardiography. RESULTS: Cigarette smoking and all systolic BP variables were associated with the presence of complex plaques (p < 0.05), whereas diastolic BP variables were not. Multiple regression analysis indicated that day-by-day mean systolic BP and day-by-day systolic BP variability remained independently associated with the presence of complex plaques (p < 0.05) after adjustment for age, male sex, cigarette smoking, hypertension, hypercholesterolemia, and diabetes mellitus. CONCLUSIONS: These findings suggest that higher day-by-day mean systolic BP and day-by-day systolic BP variability are associated with complex plaques in the aortic arch and consequently stroke risk in patients with aortic stenosis.

Enhanced method for predicting left ventricular reverse remodeling after surgical repair of aortic regurgitation: application of ultrasonic tissue characterization.

To predict left ventricular (LV) reverse remodeling after surgical repair of aortic regurgitation, we examined 30 patients with aortic regurgitation accompanying LV dilatation by myocardial tissue characterization with integrated backscatter method. Before and after operation, the magnitude of cyclic variation of integrated backscatter (CVIB) was obtained from anterior septum and posterior wall, and averaged value was calculated in each patient. Before operation, LV end-diastolic dimension, fractional shortening, and LV end-diastolic pressure were not significantly different between the patients with (group GR) and without (group PR) decreased LV end-diastolic dimension after operation. Under these conditions, CVIB, which was 9.6 +/- 1.0 dB from healthy volunteers, was significantly greater in group GR, 5.7 +/- 1.4 dB, than that in group PR, 3.8 +/- 0.8 dB (P =.0003). The patients with CVIB >/= 4 before operation were expected to have reverse remodeling after operation with a sensitivity of 79%, a specificity of 82%. These data indicate that preoperative CVIB from the left ventricle provides pivotal information for predicting reverse remodeling after operation for aortic regurgitation in addition to the conventional echocardiographic parameters.

Bicuspid aortic valve stenosis complicated by descending aortic dissection mimicking coarctation of the aorta.

We report a rare case of bicuspid aortic stenosis complicated by an ascending aortic aneurysm and aortic dissection of DeBakey type IIIb. A 35-year-old woman was admitted to our hospital to examine her systolic murmur identified at birth. Severe aortic stenosis, dilatation of the ascending aorta, and the narrow color flow signal in the descending aorta were detected by transthoracic echocardiography. Initially, coarctation of the descending aorta was suspected, but aortic dissection, DeBakey type IIIb, was revealed by transesophageal echocardiography. Transesophageal echocardiography is indicated when only insufficient information is available on valve and aortic morphology in patients with bicuspid aortic valve.