Shinpei Kimura

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.

Role of mineralocorticoid receptor on atrial structural remodeling and inducibility of atrial fibrillation in hypertensive rats

Hypertension is well known to increase atrial fibrillation (AF) and the development of AF is associated with atrial chamber remodeling. Although mineralocorticoid receptor (MR) inhibition provides cardiovascular protection, the role of MR on atrial structural remodeling and inducibility of AF in hypertension remains unclear. Here, we investigated roles of the MR on atrial structural remodeling and inducibility of AF in hypertensive rats by using MR antagonist eplerenone (EPL). Dahl salt-sensitive (DS) rats were fed a normal-salt or a high-salt (HS) diet from 7 weeks, and a non-antihypertensive dose of EPL or vehicle was administrated from 13 weeks, at which time myocytes hypertrophy, interstitial fibrosis in the atrium and AF inducibility had increased, until 20 weeks. There was no significant difference in systolic blood pressure between DS+HS (186±4 mm Hg) and DS+HS+EPL (184±5 mm Hg) at 20 weeks. Burst atrial pacing demonstrated decreased AF inducibility in DS+HS+EPL (0 of 10) compared with DS+HS (7 of 10). Fibrosis and myocytes hypertrophy in the atrium were decreased in DS+HS+EPL with the reduction of atrial inflammatory cytokines. These beneficial effects of EPL were associated with less atrial oxidative stress, as assessed by 4-hydroxy-2-nonenal staining, and reduced activation of the Rho GTPase Rac1 in the atrium. Thus, MR has important roles in atrial structural remodeling and AF inducibility in Dahl rats. The effects of MR are associated, at least in part, with activation of Rac1-oxidative stress/inflammatory axis.

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.

Inverted Takotsubo contractile pattern caused by pheochromocytoma with tall upright T-waves, but not typical deep T-wave inversion

We describe a 36-year-old woman with inverted Takotsubo cardiomyopathy caused by pheochromocytoma crisis. In the acute phase, her electrocardiogram showed ST segment depression in lead II, III, aVF and V2 through V5. On day 14, tall upright T-waves were observed in leads V2 through V5 despite heart failure and basal to midventricular ballooning improved on day 4, and all electrocardiographic abnormalities finally normalized after surgical removal of the pheochromocytomas. This is the first report of electrocardiographic course of inverted Takotsubo cardiomyopathy, and these findings seem as if the inverted electrocardiographic findings are contrary to those of apical ballooning.

Relationship Between Glucose Fluctuations and ST-Segment Resolution in Patients With ST-Elevation Acute Myocardial Infarction

This study was conducted to assess whether any relationships exist between glucose fluctuations and electrocardiographic surrogate markers of reperfusion injury in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).We prospectively studied 63 consecutive patients with STEMI undergoing primary PCI. Patients had either diabetes (n = 30), impaired glucose tolerance (n = 26), impaired fasting glucose (n = 1), or normal glucose tolerance (n = 6). STsegment resolution (STR, %) was measured using electrocardiograms recorded 60 minutes after PCI. STR was categorized as ≥ 30% and < 30%. Glucose fluctuations were assessed by the following parameters obtained from a continuous glucose monitoring system: mean amplitude of glucose excursion (MAGE, mg/dL); and area under curve with reference to mean blood glucose (AUCMBG, mg/ dL/day).Both MAGE and AUCMBG were significantly higher in STR < 30%. In univariate analysis, MAGE ≥ 70 mg/dL (OR = 17.0; 95%CI, 1.93-150.12; P < 0.01), AUCMBG ≥ 20 mg/dL/day (OR = 10.9; 95%CI, 1.92-61.77; P < 0.01), and reperfusion arrhythmias (OR = 7.6; 95%CI, 1.32-44.29; P < 0.05) were significantly associated with suboptimal STR. Multiple logistic regression analysis showed only MAGE ≥ 70 mg/dL was predictive of suboptimal STR (OR = 22.5; 95%CI, 2.43-208.66, P < 0.01).Parameters of glucose fluctuations correlated with electrocardiographic surrogate markers of impaired myocardial salvage in STEMI after reperfusion therapy. Our results suggest that glucose fluctuations may represent a potential therapeutic target to reduce myocardial reperfusion injury in STEMI.

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.