Kazuhiko Hashimura

Left Atrial Volume Combined With Atrial Pump Function Identifies Hypertensive Patients With a History of Paroxysmal Atrial Fibrillation

Identifying patients at high risk for the occurrence of atrial fibrillation is one means by which subsequent thromboembolic complications may be prevented. Left atrial enlargement is associated with progression of atrial remodeling, which is a substrate for atrial fibrillation, but impaired atrial pump function is also another aspect of the remodeling. Our objective was to differentiate patients with a history of paroxysmal atrial fibrillation using echocardiography. We studied 280 hypertensive patients (age: 66±7 years; left ventricular ejection fraction: 65±8%), including 140 consecutive patients with paroxysmal atrial fibrillation and 140 age- and sex-matched control subjects. Left atrial volume was measured using the modified Simpson method at both left ventricular end systole and preatrial contraction and was indexed to body surface area. Peak late-diastolic mitral annular velocity was measured during atrial contraction using pulsed tissue Doppler imaging as an atrial pump function. Left atrial volume index measured at left ventricular end systole had a 74% diagnostic accuracy and a 71% positive predictive value for identifying patients with paroxysmal atrial fibrillation; these values for the ratio of left atrial volume index at left ventricular end systole to the peak late-diastolic mitral annular velocity were 82% and 81%, respectively, and those for the ratio of left atrial volume index at preatrial contraction to the peak late-diastolic mitral annular velocity were 86% and 90%, respectively. In conclusion, left atrial size combined with atrial pump function enabled a more accurate diagnosis of a history of paroxysmal atrial fibrillation than conventional parameters.

Impact of Coronary Risk Factors on Contribution of Nitric Oxide and Adenosine to Metabolic Coronary Vasodilation in Humans

OBJECTIVESnThe contribution of nitric oxide (NO) and adenosine to the increase in coronary blood flow (CBF) induced by cardiac pacing was investigated in 28 subjects with angiographically normal coronary arteries with and without one or more risk factors for atherosclerosis.nnnBACKGROUNDnNO and adenosine are important in the regulation of coronary circulation, and the inhibition of NO synthesis increases adenosine production during cardiac pacing in experimental models.nnnMETHODSnCoronary artery diameters and CBF were assessed by quantitative coronary arteriography and Doppler flow velocity measurement. Plasma levels of nitrites and nitrates (NOx) (stable end products of NO), adenosine and lactate were measured, and blood gas analysis was performed.nnnRESULTSnThe extent of CBF response to cardiac pacing did not differ between the 14 subjects with and the 8 subjects without risk factors for atherosclerosis. NOx (12.0+/-0.9 vs. 14.9+/-1.1 ,amol/liter [mean+/-SD], p < 0.05), but not adenosine (50.8+/-7.2 vs. 50.8+/-6.5 nmol/liter), levels in coronary sinus blood increased in the subjects without risk factors. In contrast, adenosine (58.9+/-7.5 vs. 77.4+/-9.8 nmol/liter, p < 0.05), but not NOx (11.1+/-1.1 vs. 12.2+/-1.1 micromol/liter), levels increased in subjects with risk factors. Aminophylline, an antagonist of adenosine receptors, blunted CBF response to cardiac pacing in six subjects with risk factors. The number of risk factors showed a negative correlation (p < 0.05) with NOx production and a positive correlation (p < 0.05) with adenosine production during cardiac pacing, respectively.nnnCONCLUSIONSnNO and adenosine are increased during metabolic coronary vasodilation induced by cardiac pacing. Adenosine production may be a compensatory mechanism when NO production is reduced.

A Novel Data Mining Approach to the Identification of Effective Drugs or Combinations for Targeted Endpoints—Application to Chronic Heart Failure as a New Form of Evidence-based Medicine

SummaryBackground: Data mining is a technique for discovering useful information hidden in a database, which has recently been used by the chemical, financial, pharmaceutical, and insurance industries. It may enable us to detect the interesting and hidden data on useful drugs especially in the field of cardiovascular disease.n Methods: & Results: We evaluated the current treatments for chronic heart failure (CHF) in our institute using a decision tree method of data mining and compared the results with those of large-scale clinical trials. We enrolled 1,100 patients with CHF (NYHA classes II–IV and EF < 40%) who were hospitalized at the National Cardiovascular Center during the past 31 months. Drugs prescribed at discharge were extracted from the clinical database. Both echocardiograms and plasma BNP level at 6–12 months after discharge were determined prospectively. It was found that beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin II receptor antagonists independently improve both the plasma BNP level and %fractional shortening (FS), while oral inotropic agents increased the plasma BNP level and decreased %FS. These findings agree with evidence accumulated from several large-scale trials. Interestingly, statins, histamine receptor blockers, and alpha-glucosidase inhibitors also attenuated the severity of CHF, suggesting the possibility of new treatment of CHF.n Conclusion: Clinical data mining using Japanese CHF patients yielded almost identical data to the results of large-scale trials, and also suggested novel and unexpected candidates for CHF therapy. Further validation of the data mining approved in the cardiovascular field is warranted.

Plasma adiponectin is associated with plasma brain natriuretic peptide and cardiac function in healthy subjects.

The aim of this study was to evaluate the relationship between the plasma adiponectin level, plasma brain natriuretic peptide (BNP) level, and cardiac function in healthy subjects. We obtained clinical data and performed blood tests, including measurement of the plasma adiponectin and BNP levels, in 1,538 healthy persons from Arita-cho, a rural area of Japan. Six hundred and eight subjects also underwent echocardiography. There was a significant positive correlation between their plasma BNP and adiponectin levels in simple regression analysis (standardized regression coefficient [β]=0.34). Multivariate regression analysis revealed that the plasma adiponectin level was independently associated with the plasma BNP level (β=0.12), as well as with the age (β=0.22), male gender (β=−0.26), waist circumference (β=−0.16), and the plasma levels of high-density lipoprotein cholesterol (β=0.13), triglycerides (β=−0.16), aspartate aminotransferase (β=0.08), γ-glutamyl transpeptidase (β=−0.10), uric acid (β=−0.07), and creatinine (β=0.08). We also found a link between plasma adiponectin and the left atrial diameter index (β=0.08) or left ventricular diameter index (β=0.11), even after adjustment for age, sex, and body mass index. The plasma adiponectin level increased along with an increase of plasma BNP in healthy subjects independently of other confounding factors, demonstrating that adiponectin reflects cardiac function.

Impact of reduced left atrial functions on diagnosis of paroxysmal atrial fibrillation: Results from analysis of time-left atrial volume curve determined by two-dimensional speckle tracking

BACKGROUNDnAtrial fibrillation is commonly associated with impaired reservoir and booster functions of the left atrium (LA). Recent advances in two-dimensional speckle tracking technique (2DST) enabled automatic analysis of the time-LA volume curve representing these functions. Our objective was to evaluate LA function in patients with or without paroxysmal atrial fibrillation (PAF) using 2DST.nnnMETHODSnWe studied 111 patients (68 men, age 62 ± 16 years) with (n = 53) or without (n = 58) PAF. After constructing time-LA volume curves from the apical four and two chamber views (iE33, Philips with QLAB 6.0, Philips Medical Systems, Bothell, WA, USA), maximal LA volume (LAVmax), preatrial contraction LA volume (LAVpreA), and minimum LA volume (LAVmin) were obtained. Then, LA reservoir volume (ARV=LAVmax-LAVmin) and active emptying volume (AEV=LAVpreA-LAVmin) were calculated to determine ARV/LAVmax as reservoir function and AEV/LAVpreA as booster pump function.nnnRESULTSnPAF was associated with greater LAVmax than that in controls (80 ± 21 ml versus 65 ± 16 ml, p < 0.001) and with reduced reservoir and booster functions (ARV/LAVmax 46 ± 9% versus 52 ± 7%; AEV/LAVpreA 29 ± 10% versus 36 ± 6%, p < 0.001). Multivariate logistic analysis demonstrated that ARV/LAVmax and AEV/LAVpreA were closely associated with the existence of PAF.nnnCONCLUSIONnThese results demonstrate that the present 2DST enables determining LA reservoir and booster functions, providing insights into the diagnosis of PAF.

Heterogeneity of regional systolic function detected by tissue doppler imaging is linked to impaired global left ventricular relaxation in hypertrophic cardiomyopathy

Objective: To evaluate regional and global left ventricular (LV) function and LV wall thickness (LVWT) in patients with hypertrophic cardiomyopathy (HCM). Design and setting: Observational study at the National Cardiovascular Centre and Nagoya University Hospital in Japan. Participants: Thirty-six patients with HCM and 16 patients with hypertensive LV hypertrophy (LVH). Main outcome measures: Conventional echocardiography and strain rate (SR) imaging derived from tissue Doppler imaging were performed. Systolic strain (ϵsys), peak systolic SR (SRsys), peak early diastolic SR (SRdia) and LVWT were obtained from eight LV segments. LV pressure was simultaneously recorded with a high-fidelity micromanometer. Results: The regional ϵsys and SRsys were correlated with LVWT in patients with HCM (ru200a=u200a0.50, p<0.001 and ru200a=u200a0.63, p<0.001, respectively) but not in patients with hypertensive LVH. The standard deviations of LVWT, ϵsys and SRsys obtained from the eight LV segments of each subject were greater for patients with HCM than for patients with hypertensive LVH. The standard deviation of LVWT was correlated with those of ϵsys and SRsys (ru200a=u200a0.55, p<0.001 and ru200a=u200a0.56, p<0.001, respectively). The standard deviations of LVWT, ϵsys and SRsys were correlated with tau (ru200a=u200a0.35, p<0.05; ru200a=u200a0.47, p<0.001; and ru200a=u200a0.39, p<0.005, respectively). Conclusions: Heterogeneity of regional LV systolic function detected by SR imaging is in part attributable to heterogeneity of LVH and may be linked to impaired global LV relaxation in HCM.

Heart-type fatty acid binding protein is a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy

Objective: To determine whether concentrations of heart-type fatty acid binding protein (H-FABP) measured before hospital discharge predict critical cardiac events in patients with idiopathic dilated cardiomyopathy (DCM). Patients: 92 consecutive patients with DCM were enrolled and followed up for four years. Main outcome measures: Serum concentrations of H-FABP, brain natriuretic peptide (BNP), cardiac troponin T before hospital discharge and survival rate. Results: 23 patients died of cardiac causes, received a left ventricular assist device or underwent heart transplantation during the four-year follow up. Univariate analyses showed that New York Heart Association functional class, heart rate, ejection fraction, serum H-FABP and plasma BNP were significant variables. According to multivariate analysis, serum H-FABP and plasma BNP concentrations were independent predictors of critical cardiac events. Cardiac troponin T before hospital discharge was not a predictor. The area under the receiver operating characteristic curve for death from critical cardiac events was similar between H-FABP and BNP. Patients with an H-FABP concentration at or above the median (⩾ 5.4 ng/ml) had a significantly lower survival rate than those below the median, according to analysis by log rank test (p < 0.0001). When combined with BNP concentration at or above the median (⩾ 138 pg/ml), H-FABP below the median predicted the worst prognosis among the combinations. Conclusions: The concentration of serum H-FABP before discharge from hospital may be an independent predictor for critical cardiac events in DCM.

Abnormal Glucose Tolerance Contributes to the Progression of Chronic Heart Failure in Patients with Dilated Cardiomyopathy

Since 1) dilated cardiomyopathy (DCM) causes chronic heart failure (CHF), and 2) augmentation of neurohumoral factors such as angiotensin II impairs glucose metabolism, we examined the rate of abnormal glucose metabolism in patients having both DCM and CHF and whether correction of the impairment of glucose metabolism would improve the pathophysiology of CHF in DCM patients. A 75-g oral glucose tolerance test (OGTT) was performed in 56 patients with DCM-induced CHF and 168 age- and sex-matched control subjects. Among the CHF patients, 26.8% and 50.0% suffered from diabetes mellitus (DM) and impaired glucose tolerance (IGT), respectively, showing that abnormal glucose tolerance was more prevalent in DCM patients than in the control subjects (7.7% and 14.3%, respectively). In the patients with DCM-induced CHF, a correlation was observed between the brain natriuretic peptide (BNP) levels and the difference between the plasma glucose levels at the time of fasting and at 2 h of OGTT. Since neither DM nor IGT are thought to cause DCM, the abnormalities of glucose metabolism may be attributed to the progression of CHF. Furthermore, we tested whether correction of the abnormal glucose tolerance using voglibose (an α-glucosidase inhibitor) would improve the severity of CHF in another group of 30 patients with DCM-induced CHF and IGT. The patients treated with voglibose for 24 weeks showed decreases in left ventricular dimension, NYHA functional classification values, and plasma BNP levels, and an improvement in cardiac function. In conclusion, abnormal glucose tolerance was more prevalent among patients with DCM-induced CHF than controls, and the correction of IGT improved the pathophysiology of CHF.

Plasma B-type natriuretic peptide is a useful tool for assessing coronary heart disease risk in a Japanese general population.

B-type natriuretic peptide (BNP) has been reported to be associated with cardiovascular prognosis in a community-based population. In addition, accumulation of individual cardiovascular risk factors is important in predicting an individual’s risk of future cardiovascular disease. However, there have been few reports showing that BNP is a comprehensive marker of the accumulation of cardiovascular risk factors. We studied 1530 community-dwelling subjects without obvious heart diseases or renal dysfunction (mean age 62±15 years; 569 men and 961 women) who participated in an annual health checkup in a rural Japanese community. Coronary heart disease (CHD) risk was estimated, and patients were placed into the following three groups based on the Framingham function: low risk, moderate risk and high risk. The prevalence of moderate- and high-risk subjects for CHD rose in both genders with increasing plasma BNP levels. The area under the receiver operating characteristic curve showed a modest ability of plasma BNP levels to detect these subjects (0.755 and 0.700 for men and women, respectively). The optimal thresholds for the identification of subjects with moderate- and high-risk disease were BNP concentrations of 12.0 and 22.0u2009pgu2009ml−1, with sensitivities of 70% and 66% and specificities of 71% and 63% for men and women, respectively. In conclusion, subjects with high plasma BNP levels were at higher risk for CHD in a population without obvious heart disease or renal dysfunction.

Effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy—echocardiographical follow-up

SummaryTo evaluate the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy (DCM), two groups (Group I: 18 patients, Group II: 17 patients) with DCM divided by the order at the entry were followed echocardiographically for 16.9 ± 3.0 months in Group I and 21.4 ± 3.9 months in Group II. Metoprolol (final dose: 60 mg/day) was administered in Group I, but not in Group II (the control), although the conventional treatment for heart failure was continued. The left ventricular end-systolic dimension and ejection fraction assessed by echocardiography improved significantly after 6 months in Group I, but not in Group II, even after 48 months, although there were no significant differences in baseline data between the two groups. The end-diastolic dimension decreased significantly after 12 months in Group I only. It was estimated, using the point count method on a left ventricular endomyocardial biopsy specimen taken at entry, that the improvement (AEF) of the ejection fraction 12 months after metoprolol administration inversely correlated (r = - 0.677, p < 0.01) with percent fibrosis, indicating that the more myocardium remains, the more improvement is expected. These findings suggested a favorable effect of beta blockade in DCM, especially in cases with less fibrosis, showing that the endomyocardial biopsy could be of clinical use in selecting candidates for chronic beta-blocker therapy in DCM.