Komei Tanaka

Thromboembolism in Takotsubo cardiomyopathy

BACKGROUND Most patients with Takotsubo cardiomyopathy show a favorable outcome. Although several complications have been reported, the frequency of thromboembolism has not been clarified. METHODS Clinical characteristics and complications of 21 consecutive patients (18 female, aged 72 years) with Takotsubo cardiomyopathy during the past 9 years were investigated. RESULTS The most major complication was heart failure (52%). Thromboembolism was found in 3 patients (14%) and this was the second most frequent cardiovascular complication. One of the 3 patients showed left ventricular thrombus and the other 2 experienced cardioembolic stroke. All 3 patients visited the emergency department more than 48 h after initial chest pain occurred. CONCLUSIONS This study indicates that thromboembolism is a common complication in the acute phase of Takotsubo cardiomyopathy, and anticoagulation therapy should be performed in all patients until wall motion abnormalities improve. Takotsubo cardiomyopathy should be considered one of the important causes of cardioembolic stroke.

Expression of the peptide hormone hepcidin increases in cardiomyocytes under myocarditis and myocardial infarction

The micronutrient iron is an essential component that plays a role in many crucial metabolic reactions. The peptide hormone hepcidin is thought to play a central role in iron homeostasis and its expression is induced by iron overloading and inflammation. Recently, hepcidin has been reported to be expressed also in the heart; however, the kinetics of altered hepcidin expression in diseases of the heart remain unknown. In this study, we examined cardiac expression of hepcidin in rat experimental autoimmune myocarditis (EAM), human myocarditis and rat acute myocardial infarction (AMI). In rat EAM and AMI hearts, hepcidin was expressed in cardiomyocytes; ferroportin, which is a cellular iron exporter bound by hepcidin, was also expressed in various cells. Analysis of the time course of the hepcidin to cytochrome oxidase subunit 6a (Cox6a)2 expression ratio showed that it abruptly increased more than 100-fold in hearts in the very early phase of EAM and in infarcted areas 1 day after MI. The hepcidin/Cox6a2 expression ratio correlated significantly with that of interleukin-6/gamma-actin in both EAM and AMI hearts (r=0.781, P<.0001 and r=0.563, P=.0003). In human hearts with histological myocarditis, the ratio was significantly higher than in those without myocarditis (0.0400+/-0.0195 versus 0.0032+/-0.0017, P=.0045). Hepcidin is strongly induced in cardiomyocytes under myocarditis and MI, conditions in which inflammatory cytokine levels increase and may play an important role in iron homeostasis and free radical generation.

Inducibility of atrial fibrillation depends not on inflammation but on atrial structural remodeling in rat experimental autoimmune myocarditis

INTRODUCTION There is increasing evidence to support a link between inflammation and atrial fibrillation (AF). However, the role of inflammation on new-onset AF is still to be elucidated. METHODS Rats underwent induction of experimental autoimmune myocarditis (EAM). Atrial structural change was evaluated by echocardiography and histological analysis. Electrophysiological data and the in vivo atrial response to burst atrial pacing were evaluated in the acute (2 weeks after EAM induction) and chronic phases (8 weeks after induction). In addition, atrial pacing after 2, 4, and 6 h after lipopolysaccharide (LPS) infusion, when the expression of gap junctions was modified, were challenged with young healthy rats. RESULTS AF was induced in 11 of 15 chronic phase EAM rats but not in either acute phase EAM rats or LPS infusion rats (P<.01). Echocardiography showed dilatation of both atrium and ventricle and a decrease in the ejection fraction in the chronic phase. Histology revealed severe inflammatory lesions only in the acute phase. Interstitial atrial fibrosis as well as the area of atrial myocyte increased in the chronic phase but not in the acute phase. CONCLUSIONS AF could be induced in the chronic phase of myocarditis rats, but not in the acute phase of myocarditis rats or in rats with LPS infusion. Acute inflammation per se did not increase the occurrence of AF induction. Atrial structural remodeling caused by inflammation and hemodynamic effects is necessary to induce AF.

Sulfated Polysaccharide Fucoidan Ameliorates Experimental Autoimmune Myocarditis in Rats

Homing of cardiac myosin-specific CD4-positive T cells into the myocardium is the initial pathologic event of experimental autoimmune myocarditis (EAM). Subsequently, various bystander inflammatory cells are recruited into the myocardium crossing vascular endothelial cell walls. Sulfated polysaccharide fucoidan binds selectin nonselectively and blocks its function. Therefore, this study was designed to evaluate whether in vivo fucoidan treatment can improve EAM. A 21-day infusion of physiological saline or fucoidan was administrated intraperitoneally to the rats with sham operation (sham-saline, n = 5; sham-fucoidan, n = 6) or those with cardiac myosin injection (EAM-saline, n = 10; EAM-fucoidan, n = 10). After 3 weeks, fucoidan treatment improved left ventricular ejection fraction (79.04 ± 2.81 vs 65.94% ± 3.22%; P < .01 vs EAM-saline) with a reduced ratio of heart weight to body weight (4.016 ± 0.239 vs 4.975 ± 0.252 mg/g; P < .05 vs EAM-saline) in EAM. Furthermore, fucoidan treatment decreased serum levels of BNP (292.0 ± 53.4 vs 507.4 ± 89.2 ng/mL; P < .05 vs EAM-saline) and the myocarditis area (31.66 ± 1.53 vs 42.51% ± 3.24%; P < .01 vs EAM-saline) in EAM. These beneficial effects of fucoidan were accompanied by inhibition of both macrophage and CD4-positive T-cell infiltration into the myocardium. Fucoidan, a nonselective selectin blocker, attenuates the progression of EAM. This observation may be explained, at least in part, by blocking the extravasation of inflammatory cells into the myocardium.

Mechanical alternans in human idiopathic dilated cardiomyopathy is caused with impaired force-frequency relationship and enhanced poststimulation potentiation.

Mechanical alternans (MA) is frequently observed in patients with heart failure, and is a predictor of cardiac events. However, there have been controversies regarding the conditions and mechanisms of MA. To clarify heart rate-dependent contractile properties related to MA, we performed incremental right atrial pacing in 17 idiopathic dilated cardiomyopathy (DCM) patients and in six control patients. The maximal increase in left ventricular dP/dt during pacing-induced tachycardia was assessed as the force gain in the force–frequency relationship (FG-FFR), and the maximal increase in left ventricular dP/dt of the first post-pacing beats was examined as the force gain in poststimulation potentiation (FG-PSP). As a result, MA was induced in 9 DCM patients (DCM MA(+)) but not in the other 8 DCM patients (DCM MA(−)), and not in any of the control patients. DCM MA(+) had significantly lower FG-FFR (34.7 ± 40.9 vs 159.4 ± 103.9 mmHg/s, P = 0.0091) and higher FG-PSP (500.0 ± 96.8 vs 321.9 ± 94.9 mmHg/s, P = 0.0017), and accordingly a wider gap between FG-PSP and FG-FFR (465.3 ± 119.4 vs 162.5 ± 123.6 mmHg/s, P = 0.0001) than DCM MA(−) patients. These characteristics of DCM MA(+) showed clear contrasts to those of the control patients. In conclusion, MA is caused with an impaired force–frequency relationship despite significant poststimulation potentiation, suggesting that MA reflects ineffective utilization of the potentiated intrinsic force during tachycardia.

Comparative Effects of Olmesartan and Azelnidipine on Atrial Structural Remodeling in Spontaneously Hypertensive Rats

The differential effects between olmesartan (OM), an angiotensin 2 type 1 receptor blocker (ARB), and azelnidipine (AZ), a calcium channel blocker (CCB), on atrial structural remodeling were studied in spontaneously hypertensive rats (SHR). Eight weeks after treatment, both OM and AZ decreased systolic blood pressure to similar levels. Histological analysis revealed that both OM and AZ had decreased the size of the atrial myocytes and interstitial fibrosis in the atrium, and that the effects of OM were greater than those of AZ. These beneficial effects of OM were associated with less atrial oxidative stress, as assessed by 3-nitrotyrosine staining, and less activation of Rac1, a regulatory component in NADPH oxidase. These results suggest that the ARB was more effective than the CCB in ameliorating atrial structural remodeling due to the suppression of oxidative stress.

Significance of Sarcopenia Evaluation in Acute Decompensated Heart Failure

In patients with chronic heart failure (HF), the clinical importance of sarcopenia has been recognized in relation to disease severity, reduced exercise capacity, and adverse clinical outcome. Nevertheless, its impact on acute decompensated heart failure (ADHF) is still poorly understood. Dual-energy X-ray absorptiometry (DXA) is a technique for quantitatively analyzing muscle mass and the degree of sarcopenia. Fat-free mass index (FFMI) is a noninvasive and easily applicable marker of muscle mass.This was a prospective observational cohort study comprising 38 consecutive patients hospitalized for ADHF. Sarcopenia, derived from DXA, was defined as a skeletal muscle mass index (SMI) two standard deviations below the mean for healthy young subjects. FFMI (kg/m2) was calculated as 7.38 + 0.02908 × urinary creatinine (mg/day) divided by the square of height (m2).Sarcopenia was present in 52.6% of study patients. B-type natriuretic peptide (BNP) levels were significantly higher in ADHF patients with sarcopenia than in those without sarcopenia (1666 versus 429 pg/mL, P < 0.0001). Receiver operator curves were used to compare the predictive accuracy of SMI and FFMI for higher BNP levels. Areas under the curve for SMI and FFMI were 0.743 and 0.717, respectively. Multiple logistic regression analysis showed sarcopenia as a predictor of higher BNP level (OR = 18.4; 95% CI, 1.86-181.27; P = 0.013).Sarcopenia is associated with increased disease severity in ADHF. SMI based on DXA is potentially superior to FFMI in terms of predicting the degree of severity, but FFMI is also associated with ADHF severity.

Manifestation of latent left ventricular outflow tract obstruction caused by acute myocardial infarction: An important complication of acute myocardial infarction

BACKGROUND Although transient left ventricular outflow tract (LVOT) obstruction is reported as a complication with acute myocardial infarction (AMI), the mechanisms and features of LVOT obstruction in AMI are unclear. METHODS AND RESULTS Herein, we present two cases of transient LVOT obstruction with anteroseptal AMI. The features of these two cases were one-vessel disease (1-VD) of the left anterior descending artery (LAD) and maintenance of blood flow to the major septal branch (SB). Moreover, LVOT obstruction was revealed after dobutamine infusion in the chronic phase and the aorto-septal angle was low in these two cases, meaning that latent LVOT obstruction was due to sigmoid-shaped septum. CONCLUSIONS Latent LVOT obstruction would be manifested in the acute phase of AMI. 1-VD of LAD and the maintenance of major SB blood flow are important factors with respect to the manifestation of latent LVOT obstruction.

Intravascular Ultrasonic Imaging of Vulnerable Plaque in a Bare Metal Stent 10 Years After Implantation

A 77-year-old woman was admitted to our hospital with unstable angina pectoris. She was previously diagnosed as having both mitral valve regurgitation and aortic valve stenosis and underwent surgery for replacement of both valves when she was 61 years of age. At 66 years of age, she was admitted to our hospital for angina pectoris and underwent implantation of a bare metal stent (BMS; 3.5×15 mm, Multilink, Guidant, Santa Clara, Calif) at the proximal left anterior descending coronary artery. Her …

Long-term carperitide treatment attenuates left ventricular remodeling in rats with heart failure after autoimmune myocarditis.

The effect of carperitide, recombinant human atrial natriuretic peptide, on chronic heart failure (HF) has not been clarified. We investigated the beneficial effects of chronic carperitide treatment in rats with HF after experimental autoimmune myocarditis. A 28-day infusion of carperitide (n = 14) or vehicle (n = 14) was administrated to the rats 4 weeks after experimental autoimmune myocarditis induction. After 4 weeks, the myocardial levels of cyclic guanosine monophosphate (cGMP), left ventricular function, myocyte hypertrophy, interstitial fibrosis, myocardial capillary vessel density, and activity of one prominent substrate of cGMP, vasodilator-stimulated phosphoprotein (VASP) that may enhance angiogenesis, were measured. Carperitide treatment increased the myocardial levels of cGMP and attenuated the functional severity along with a decreased myocyte cross-sectional area, interstitial fibrosis, and an increased capillary to myocyte ratio. Furthermore, carperitide treatment enhanced the phosphorylation of VASP at Ser239, which was preferentially phosphorylated by cGMP-dependent protein kinase but not Ser157, which was preferentially phosphorylated by cyclic adenosine monophosphate-dependent protein kinase. Long-term carperitide treatment attenuates ventricular remodeling and ameliorates the progression of chronic HF. The effects of carperitide treatment are associated with increased neovascularization among the residual myocytes and an increase of VASP activation.