Yoshio Taketani

Index-Beat Assessment of Left Ventricular Systolic and Diastolic Function during Atrial Fibrillation Using Myocardial Strain and Strain Rate

BACKGROUND Accurate assessment of left ventricular (LV) function in patients with atrial fibrillation (AF) remains difficult, mainly because of the beat-to-beat variability of many echocardiographic parameters. The aim of this study was to assess the hypothesis that LV function can be estimated from an index-beat echocardiographic assessment in patients with AF using myocardial strain and strain rate. METHODS A prospective study was conducted to assess 25 patients with AF (mean age, 66 ± 10 years). Peak systolic longitudinal strain (LS) and peak diastolic longitudinal strain rate (dSR) were measured using two different methods: (1) mean LS and dSR, the averages of instantaneous LS and dSR over 10 sec, and (2) index-beat LS and dSR, calculated when the ratio of the preceding (RR1) to the pre-preceding (RR2) interval was 1 (range, 0.96-1.04). These variables were compared with simultaneously measured LV pressure parameters using Millar catheters. RESULTS There was a positive linear relationship between mean LS and index-beat LS at RR1/RR2 = 1 (r = 0.94, P < .001) and a positive linear relationship between mean dSR and index-beat dSR (r = 0.69, P < .001). Index-beat LS was correlated with the maximal positive derivative of LV pressure (peak +dP/dt) (r = -0.73, P < .001). Index-beat dSR was correlated with the time constant of isovolumic LV pressure decay (τ) (r = -0.63, P < .001). To investigate the independent predictors of τ, a stepwise multilinear regression analysis showed that index-beat dSR was the best predictor of τ. CONCLUSIONS Index-beat parameters accurately reflect the mean values of parameters in patients with AF. These noninvasively obtained index-beat parameters are useful to assess surrogate LV function even in patients with AF.

Elevated concentrations of pentraxin 3 are associated with coronary plaque vulnerability

BACKGROUND Inflammation is a critical contributing factor to the development and progression of atherosclerosis. Pentraxin 3 (PTX3) is produced abundantly in atherosclerotic lesions while C-reactive protein (CRP) is mainly produced in the liver. In this study, we investigated whether plasma levels of PTX3 might be a sensitive marker both for the severity of coronary artery disease and vulnerable plaques. Next, we determined whether assays for inflammatory molecules can be used to monitor the therapeutic effects of telmisartan on stabilization of vulnerable atherosclerotic plaques. METHODS AND RESULTS We measured PTX3 concentrations in the peripheral and coronary sinus plasma of 40 patients with angina pectoris (AP) and 20 control subjects. Next, in 28 patients with AP, we determined the correlation between levels of inflammatory molecules and the computed tomography (CT) density of plaques as a quantitative index of plaque vulnerability. There was no significant difference in peripheral plasma PTX3 concentrations between patients with AP and control subjects, while coronary sinus plasma PTX3 concentrations were significantly higher in AP patients than control subjects. The concentrations of PTX3 in coronary sinus and peripheral plasma correlated with Gensini scores as an index of severity of coronary atherosclerosis. Interestingly, there was a significantly negative correlation between plasma PTX3 concentrations and CT density (r=-0.67, p<0.01). On the other hand, CT density did not correlate with the peripheral plasma concentrations of monocyte chemoattractant protein-1 (MCP-1) or high-sensitivity CRP (hsCRP). Furthermore, telmisartan treatment for 6 months decreased plasma concentrations of PTX3 but not those of MCP-1 or hsCRP in 12 patients with essential hypertension. Multivariate regression analysis revealed that changes in PTX3 levels were independent of blood pressure changes. CONCLUSIONS PTX3 is likely more specific than hsCRP as an indicator of coronary plaque vulnerability that could lead to plaque rupture.

Gender disparities in the association between epicardial adipose tissue volume and coronary atherosclerosis: A 3-dimensional cardiac computed tomography imaging study in Japanese subjects

BackgroundGrowing evidence suggests that epicardial adipose tissue (EAT) may contribute to the development of coronary artery disease (CAD). In this study, we explored gender disparities in EAT volume (EATV) and its impact on coronary atherosclerosis.MethodsThe study population consisted of 90 consecutive subjects (age: 63 ± 12 years; men: 47, women: 43) who underwent 256-slice multi-detector computed tomography (MDCT) coronary angiography. EATV was measured as the sum of cross-sectional epicardial fat area on CT images, from the lower surface of the left pulmonary artery origin to the apex. Subjects were segregated into the CAD group (coronary luminal narrowing > 50%) and non-CAD group.ResultsEATV/body surface area (BSA) was higher among men in the CAD group than in the non-CAD group (62 ± 13 vs. 33 ± 10 cm3/m2, p < 0.0001), but did not differ significantly among women in the 2 groups (49 ± 18 vs. 42 ± 9 cm3/m2, not significant). Multivariate logistic analysis showed that EATV/BSA was the single predictor for >50% coronary luminal narrowing in men (p < 0.0001). Predictors excluded were age, body mass index, hypertension, diabetes mellitus, and hyperlipidemia.ConclusionsIncreased EATV is strongly associated with coronary atherosclerosis in men.

Effects of the Addition of Eicosapentaenoic Acid to Strong Statin Therapy on Inflammatory Cytokines and Coronary Plaque Components Assessed by Integrated Backscatter Intravascular Ultrasound

BACKGROUND The effects of eicosapentaenoic acid (EPA) on coronary artery disease have been previously reported; however, those of the addition of EPA to strong statins on coronary plaque components and local inflammatory cytokines are not known. METHODSANDRESULTS A total of 95 patients who had been treated with strong statin for at least 6 months were randomized into 2 groups: an EPA group (additional treatment with EPA at 1,800 mg/day, n=48) or a control group (no additional treatment, n=47), for 6 months. The tissue characteristics of target coronary plaque in each patient were analyzed using IB-IVUS before and after treatment. We also measured plasma levels of inflammatory cytokines sampled in the coronary sinus (CS) and peripheral vein.A significant reduction in lipid volume (18.5 ± 1.3 to 15.0 ± 1.5 mm(3), P=0.007) and a significant increase in fibrous volume (22.9 ± 0.8 to 25.6 ± 1.1 mm(3), P=0.01) were observed in IB-IVUS image analyses in the EPA group, but no significant changes in the plaque components in the control group. CS levels of pentraxin 3 and monocyte chemoattractant protein-1 were lower after than before treatment with EPA (3.3 ± 2.1 to 2.6 ± 1.2 ng/ml, 120.4 ± 26.2 to 110.2 ± 26.8 pg/ml, P=0.015 and P=0.008, respectively); however, there were no significant changes in those inflammatory cytokines between pre- and post-treatment in the control group. CONCLUSIONS The addition of EPA was associated with reduced lipid volume in coronary plaques and decreased inflammatory cytokines.

Percutaneous coronary intervention using a virtual 3-Fr guiding catheter†

Background: We have recently reported a novel percutaneous coronary intervention (PCI) system using a hydrophilic‐coated sheathless guiding catheter (Virtual 3‐Fr, Medikit, Tokyo, Japan), which provides us with less invasive angioplasty and a puncture site injury equivalent to a conventional 3‐Fr introducer sheath. Here, we report the initial results of PCI using this novel system. Methods: A total of 36 coronary artery lesions of 27 patients were treated by using a virtual 3‐Fr PCI system. Procedural outcomes of virtual 3‐Fr PCI were retrospectively evaluated. Results: The mean age was 73.0 ± 8.7 years (range, 46–84 years), and 15 were men (56%). Access sites included the radial artery in 18 patients (67%), the brachial artery in eight patients (30%), and the femoral artery in 1 patients (4%). Among 36 lesions, seven were chronic total occlusions, and a virtual 3‐Fr PCI was successful in 33 lesions (92%). Among the successfully treated 33 lesions, coronary stents were deployed in 32 (97%), and intravascular ultrasound examination was performed in 19 (58%). Hemostasis was achieved immediately after PCIs in all cases. No access‐site related complications including radial artery occlusion were observed. Conclusions: The performance of a virtual 3‐Fr PCI system appears to be comparable to one using a regular 5‐Fr guiding catheter while the puncture‐site damage remains equivalent to that of a 3‐Fr introducer sheath. Virtual 3‐Fr PCI may have a potential to serve as a minimally invasive strategy for the treatment of coronary artery diseases.

Interval from the onset of transmitral flow to annular velocity is a marker of LV filling pressure.

Recently, the time interval between the onset of early diastolic transmitral flow velocity (E) and mitral annular velocity (e′) (TE-e′) was proposed as a new index representing left ventricular (LV) relaxation. A problem with the measurement of TE-e′ was that E and e′ could not be measured

Plasma microRNA-100 is associated with coronary plaque vulnerability.

BACKGROUND Although numerous studies have reported altered plasma levels of various microRNAs (miRNAs) in patients with cardiovascular disease, there are no data on the relationship between plasma miRNAs and vulnerable coronary plaque. In this study, we investigated whether plasma miRNAs might be a sensitive marker of coronary plaque vulnerability. METHODS AND RESULTS Integrated backscatter intravascular ultrasound (IB-IVUS) was performed in 32 consecutive patients with angina pectoris who underwent percutaneous coronary intervention. Three-dimensional analysis of IB-IVUS was performed to determine the percentage of lipid volume (%LV) and fibrous volume (%FV). Circulating miRNAs were measured in EDTA-plasma simultaneously obtained from the aorta and the coronary sinus (CS). Muscle-enriched (miR-133a, miR-208a, miR-499), vascular-enriched (miR-92a, miR-100, miR-126, miR-127, miR-145), and myeloid cell-enriched miRNAs (miR-155, miR-223) were measured. Plasma miR-100 was higher in the CS than in the aorta, but there were no significant differences in the levels of other miRNAs between the aorta and CS. Plasma miR-100 in the aorta was positively correlated with %LV (r=0.48, P<0.01) and negatively correlated with %FV (r=-0.41, P<0.05). Importantly, transcoronary concentration gradient of circulating miR-100 was more strongly correlated with %LV (r=0.53, P<0.01) and %FV (r=-0.56, P<0.01). CONCLUSIONS miR-100 might be released into the coronary circulation from vulnerable coronary plaques. This study provides insights into the role of miRNAs in coronary atherosclerotic disease.

Pentraxin 3 is a local inflammatory marker in atrial fibrillation

Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF). Pentraxin 3 (PTX3) is produced abundantly in local inflammatory lesions while C-reactive protein (CRP) is produced mainly in the liver. In this study, we investigated whether a local level of PTX3 might be a sensitive marker for the local inflammation of AF. Blood from the periphery and left atrial appendage (LAA) was sampled from 23 patients with AF undergoing pulmonary vein isolation, and from 10 control subjects with Wolff–Parkinson–White syndrome. We measured peripheral and LAA plasma concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and PTX3. Plasma PTX3 concentrations in both locations were higher in patients with AF than in control subjects. PTX3 concentrations were significantly higher in the LAA than the periphery in patients with AF (3.7 ± 1.4 vs 3.3 ± 1.2 ng/ml, P < 0.01), but not in control subjects (2.4 ± 0.5 vs 2.4 ± 0.5 ng/ml, not significant). Patients and controls showed no significant differences in CRP, IL-6, or TNF-α concentrations between the periphery and LAA. Interestingly, there was a significant positive correlation between LAA plasma concentrations of PTX3 and left atrial volume (r = 0.55, P < 0.01). These data demonstrate that Local PTX3 production in the left atrium might reflect the local inflammation of AF.

Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein

Vagal nerve stimulation has been postulated to confer an antifibrillatory effect. We studied whether ghrelin administration would exert an antiarrhythmic effect via modulation of autonomic nerve activity in rats after acute myocardial ischemia (MI). Male Sprague-Dawley rats were exposed to 30 min of ischemia following ligation of the left coronary artery. Animals were then randomized to receive either ghrelin (n = 26) or saline (n = 26) during the period of coronary ligation. Power spectral analysis of heart-rate variability revealed that the administration of ghrelin increased the high-frequency (HF) power and decreased the low-frequency (LF)/HF ratio. Ventricular tachyarrhythmias were less frequent in rats after MI who received ghrelin in comparison with rats that received saline. Immunoblotting and immunohistochemistry revealed that rats given saline alone during MI exhibited a marked reduction in phosphorylated connexin-43 within the left ventricle, whereas those that received ghrelin displayed only minor reductions in comparison with sham-operated rats. These effects of ghrelin were diminished by the coadministration of atropine or the blockade of vagal afferents. These data demonstrate that the beneficial effect of ghrelin might be mediated by modulation of cardiac autonomic nerve activity.

Renoprotective and antioxidant effects of cilnidipine in hypertensive patients

Cilnidipine, an L/N-type calcium channel blocker (CCB), has been reported to have more beneficial effects on proteinuria progression in hypertensive patients than amlodipine, an L-type CCB. The N-type calcium channel blockade that inhibits renal sympathetic nerve activity might reduce glomerular hypertension by facilitating vasodilation of the efferent arterioles. However, the precise mechanism of the renoprotective effect of cilnidipine remains unknown. Because cilnidipine exerted significantly higher antioxidant activity than amlodipine in cultured human mesangial cells, we hypothesized that cilnidipine might exert a renoprotective effect by suppressing oxidative stress. A total of 35 hypertensive patients receiving a renin–angiotensin system inhibitor were randomly assigned to a cilnidipine (n=18; 10 mg per day cilnidipine titrated to 20 mg per day) or amlodipine (n=17; 5 mg per day amlodipine titrated to 10 mg per day) group; the target blood pressure (BP) was set at 130/85 mmHg. After 6 months of treatment, systolic and diastolic BPs were significantly reduced in both of the groups, without any significant difference between the groups. The urinary albumin, 8-hydroxy-2′-deoxyguanosine (OHdG) and liver-type fatty-acid-binding protein (L-FABP) to creatinine ratios significantly decreased in the cilnidipine group (P<0.05) compared with those in the amlodipine group. The reductions in urinary albumin, 8-OHdG and L-FABP were not correlated with the change in systolic BP. In conclusion, cilnidipine, but not amlodipine, ameliorated urinary albumin excretion and decreased urinary 8-OHdG and L-FABP in the hypertensive patients. Cilnidipine probably exerts a greater renoprotective effect through its antioxidative properties.