Takahiro Ohara

Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): two randomised trials.

BACKGROUND Patients who have acute myocardial infarction remain at major risk of cardiovascular events. We aimed to assess the effects of either human atrial natriuretic peptide or nicorandil on infarct size and cardiovascular outcome. METHODS We enrolled 1216 patients who had acute myocardial infarction and were undergoing reperfusion treatment in two prospective, single-blind trials at 65 hospitals in Japan. We randomly assigned 277 patients to receive intravenous atrial natriuretic peptide (0.025 microg/kg per min for 3 days) and 292 the same dose of placebo. 276 patients were assigned to receive intravenous nicorandil (0.067 mg/kg as a bolus, followed by 1.67 microg/kg per min as a 24-h continuous infusion), and 269 the same dose of placebo. Median follow-up was 2.7 (IQR 1.5-3.6) years for patients in the atrial natriuretic peptide trial and 2.5 (1.5-3.7) years for those in the nicorandil trial. Primary endpoints were infarct size (estimated from creatine kinase) and left ventricular ejection fraction (gauged by angiography of the left ventricle). FINDINGS 43 patients withdrew consent after randomisation, and 59 did not have acute myocardial infarction. We did not assess infarct size in 50 patients for whom we had fewer than six samples of blood. We did not have angiographs of left ventricles in 383 patients. Total creatine kinase was 66,459.9 IU/mL per h in patients given atrial natriuretic peptide, compared with 77,878.9 IU/mL per h in controls, with a ratio of 0.85 between these groups (95% CI 0.75-0.97, p=0.016), which indicated a reduction of 14.7% in infarct size (95% CI 3.0-24.9%). The left ventricular ejection fraction at 6-12 months increased in the atrial natriuretic peptide group (ratio 1.05, 95% CI 1.01-1.10, p=0.024). Total activity of creatine kinase did not differ between patients given nicorandil (70 520.5 IU/mL per h) and controls (70 852.7 IU/mL per h) (ratio 0.995, 95% CI 0.878-1.138, p=0.94). Intravenous nicorandil did not affect the size of the left ventricular ejection fraction, although oral administration of nicorandil during follow-up increased the left ventricular ejection fraction between the chronic and acute phases. 29 patients in the atrial natriuretic peptide group had severe hypotension, compared with one in the corresponding placebo group. INTERPRETATION Patients with acute myocardial infarction who were given atrial natriuretic peptide had lower infarct size, fewer reperfusion injuries, and better outcomes than controls. We believe that atrial natriuretic peptide could be a safe and effective adjunctive treatment in patients with acute myocardial infarction who receive percutaneous coronary intervention.

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.

Utility of gallium-67 scintigraphy for evaluation of cardiac sarcoidosis with ventricular tachycardia.

BackgroundThe outcome of cardiac sarcoidosis is sometimes very poor. Ventricular tachycardia (VT) associated with cardiac sarcoidosis is the most common cause of sudden death among most patients. However, there is no established method for potential VT in patients with cardiac sarcoidosis. Thus, we investigated the utility of evaluation of gallium-67 scintigraphy for potential VT in patients with cardiac sarcoidosis.Methods and ResultsCardiac sarcoidosis was diagnosed in 25 patients at ours or collaborating hospitals during the period 1982 through 2004. Twenty-one of these patients were treated with corticosteroid, and these patients were divided into two groups, depending on whether VT was present: a non-VT group (n=7) and a VT group (n=14). Laboratory and gallium-67 scintigraphy findings were examined in both groups. During the follow-up period, initial and maintenance dosages of corticosteroid did not differ significantly between the groups. Accumulation of gallium-67 in the heart at the time of diagnosis was detected more frequently in the VT group than in the non-VT group (14.3 vs. 71.4%, p<0.05). Six of the seven VT patients who underwent follow-up examination showed improvement on the scintigram obtained after treatment. Five of the six showed no VT recurrence in terms of Holter electrocardiogram, electrophysiologic study, or delivery of implantable cardioverter defibrillator shock. Serum angiotensin-converting enzyme and lysozyme concentrations were within normal limits in most patients in both groups.ConclusionsActivity of sarcoid granulomas may be associated with the occurrence of VT. Gallium-67 scintigraphy reflects the activity of sarcoid granulomas and thus is useful for evaluation of cardiac sarcoidosis in patients with potential VT.

Loss of Adrenergic Augmentation of Diastolic Intra-LV Pressure Difference in Patients With Diastolic Dysfunction : Evaluation by Color M-Mode Echocardiography

OBJECTIVES The aim of this study was to evaluate the hypothesis that the adrenergic response of the intraventricular pressure difference (IVPD) is reduced in patients with preserved ejection fraction (EF) and diastolic dysfunction (DD). BACKGROUND In early diastole, there is a progressive IVPD extending from the left atrium (LA) to the left ventricular (LV) apex. In response to adrenergic stimulation, as occurs during exercise, the IVPD increases allowing rapid filling without an abnormal increase in LA pressure. Patients with heart failure with a reduced EF have impaired adrenergic augmentation of the IVPD. METHODS We studied 166 consecutive patients undergoing dobutamine stress echocardiography who had no inducible ischemia and an EF ≥50%, of which 21 had normal diastolic function, 14 had impaired relaxation (grade 1), 80 had pseudonormal filling (grade 2), and 51 had restrictive filling (grade 3). Color M-mode Doppler (CMMD) images of mitral inflow were obtained at rest and during low (10 μg/kg/min) and peak (20 to 40 μg/kg/min) doses of dobutamine. The total IVPD from the LA to LV apex, LA to mid-LV, and mid-LV to the LV apex were calculated using the CMMD data to integrate the Euler equation. RESULTS Total IVPD was not different between groups at rest. With dobutamine, the total IVPD increased by 2.20 ± 1.95 mm Hg in normal subjects and by only 0.73 ± 1.33 mm Hg, 1.84 ± 1.63 mm Hg, and 1.08 ± 1.57 mm Hg in patients with grades 1, 2, and 3 DD, respectively. This difference was due to a failure in augmentation of IVPD from the mid-LV to the LV apex, indicating reduced apical ventricular suction with DD, whereas the IVPD from the LA to the mid-LV responded similarly to dobutamine in normal subjects and those with DD. CONCLUSIONS In patients with preserved EF, DD is associated with a reduced adrenergic augmentation of the IVPD from the mid-LV to the LV apex, reflecting less apical suction.

Evaluation of LV Diastolic Function From Color M-Mode Echocardiography

OBJECTIVES this study evaluated early diastolic filling dynamics using a semiautomated objective analysis of filling velocities obtained from color M-mode echocardiography. BACKGROUND diastolic function can be evaluated from color M-mode echocardiography by measuring the early diastolic flow propagation velocity (Vp) from the slope of a single linear approximation of an isovelocity contour. However, this method has limitations and may not accurately represent diastolic filling. METHODS we used a semiautomated objective analysis of color M-mode echocardiograms from a development cohort of 125 patients with varying diastolic function to quantify left ventricular filling velocities. Early diastolic filling was not accurately described with a single propagation velocity; instead, the rapid initial filling velocity abruptly decelerated to a slower terminal velocity. Then, we evaluated a new measure of diastolic function in a separate group of 160 patients. RESULTS compared with normal filling, diastolic dysfunction with restricted filling had a lower initial velocity (53 ± 21 cm/s vs. 87 ± 29 cm/s, p < 0.001), and the deceleration point occurred closer to the mitral annulus (2.4 ± 0.6 cm vs. 3.1 ± 0.7 cm, p < 0.05). The product of the initial velocity and the distance to the deceleration point from the mitral annulus, indicating the strength of the early filling (Vs), was progressively reduced with diastolic dysfunction. In a separate validation cohort of 160 patients, Vs better recognized diastolic dysfunction (classified by reduced diastolic intraventricular pressure gradient, elevated pulmonary capillary wedge pressure, or elevated B-type natriuretic peptide) than Vp did. CONCLUSIONS early diastolic flow propagation occurs with an initial rapid velocity that abruptly decelerates to a terminal velocity. With diastolic dysfunction, the initial velocity is slower and the deceleration point occurs closer to the mitral annulus than with normal filling. A new parameter that combines these 2 effects (Vs) provides a more accurate assessment of diastolic function than the conventional propagation velocity.

Pathophysiological impact of serum fibroblast growth factor 23 in patients with nonischemic cardiac disease and early chronic kidney disease

Although the important role of fibroblast growth factor (FGF)23 on cardiac remodeling has been suggested in advanced chronic kidney disease (CKD), little is known about serum (s)FGF23 levels in patients with heart failure (HF) due to nonischemic cardiac disease (NICD) and early CKD. The present study aimed to investigate sFGF23 levels in NICD patients and identify the responsible factors for the elevation of sFGF23 levels. We prospectively measured sFGF23 levels in consecutive hospitalized NICD patients with early CKD (estimated glomerular filtration rate ≥ 40 ml·min(-1)·1.73 m(-2)) and analyzed the data of both echocardiography and right heart catheterization. Of the 156 NICD patients (estimated glomerular filtration rate range: 41-128 ml·min(-1)·1.73 m(-2)), the most severe HF symptom (New York Heart Association class III-IV, 53% vs. 33%, P = 0.015) was found in the above median sFGF23 (39.1 pg/ml) group compared with the below median sFGF23 group. sFGF23 levels were higher in patients with HF hospitalization history compared with those without HF [median: 46.8 (interquartile range: 38.8-62.7) vs. 34.7 (interquartile range: 29.6-42.4) pg/ml, P < 0.0001]. In the multivariate analysis, HF hospitalization was independently related to elevated sFGF23 levels (P = 0.022). Both systolic dysfunction and high plasma aldosterone concentration were identified as predictors of high sFGF23 levels (P < 0.05). Among the neurohormonal parameters, elevated sFGF23 levels were the only factor to predict a declining left ventricular ejection fraction (P = 0.001). These findings suggest that the progression of HF per se contributes to the elevation of sFGF23 levels even in the early stages of CKD, which leads to further myocardial dysfunction, potentially creating a vicious cycle.

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.

Evolving focus on diastolic dysfunction in patients with coronary artery disease.

Purpose of review The purpose of this review is to summarize recent studies of coronary artery disease (CAD) and diastolic dysfunction. Recent findings Myocardial ischemia slows ventricular relaxation and can impair ventricular distensibility resulting in diastolic dysfunction apparent as abnormal left ventricular (LV) filling dynamics that can be recognized noninvasively. As such, the development of diastolic dysfunction during stress testing may improve the recognition of CAD. The noninvasive recognition of diastolic dysfunction indicates a poor prognosis in patients with an acute coronary syndrome and chronic CAD. Patients with heart failure with preserved ejection fraction (HFpEF) frequently have CAD, and it may contribute to the heart failure. Summary Myocardial ischemia produces diastolic dysfunction. The evaluation of diastolic dysfunction has diagnostic and prognostic roles in the management of CAD. CAD is a frequent and important comorbidity of HFpEF.

Clinical predictors of in-hospital death and early surgery for infective endocarditis: Results of CArdiac Disease REgistration (CADRE), a nation-wide survey in Japan

BACKGROUND The benefit of early surgery for IE is yet to be determined in non-Western countries. We conducted this study to evaluate the role of early surgery in infective endocarditis (IE) in Japan. METHODS IE admissions in Japan were prospectively registered using a nation-wide WEB-based registration system (CArdiac Disease REgistration, CADRE). The impact of early surgery on in-hospital mortality was assessed in native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE). Risk factors for in-hospital death were assessed by multiple logistic regression analysis. The propensity score for early surgery was calculated to adjust the impact of early surgery. RESULTS From September 2006 to May 2009, 348 NVE and 81 PVE were registered. In NVE, early surgery was preferable in every quartile stratified with the propensity score and the summary odds ratio (OR) and 95% confidence interval (CI) was 0.12 (0.05-0.31). The predictors of in-hospital death were Staphylococcus aureus infection (OR 3.5, 95% CI 1.26-9.7), heart failure (OR 6.74, 95% CI 2.43-18.7) and early surgery (OR 0.07, 95% CI 0.03-0.2). In PVE, the predictors of in-hospital death were age (OR 1.09, 95% CI 1.01-1.18), S. aureus infection (OR 5.8, 95% CI 1.4-24.01) and heart failure (OR 7.44, 95% CI 1.81-30.67), whereas early surgery was not (OR 0.51, 95% CI 0.12-2.16). CONCLUSION Early surgery for NVE is associated with improved survival in a wide range of clinical subgroups in Japan. In PVE a survival benefit of early surgery is not clear.

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

BACKGROUND Atrial 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. METHODS We 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. RESULTS PAF 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. CONCLUSION These results demonstrate that the present 2DST enables determining LA reservoir and booster functions, providing insights into the diagnosis of PAF.