Improvement of Mass Lesions around Coronary Arteries and Fractional Flow Reserve after Steroid Therapy in Immunoglobulin-G4-related Coronary Periarteritis.

Immunoglobulin-G4-related disease (IgG4-RD) is a multi-organ systemic inflammatory disorder. The ideal treatment of coronary artery involvement in IgG4-RD remains uncertain due to its rarity. We herein report a case of coronary artery involvement with IgG4-RD, wherein mass lesions surrounded the coronary arteries with a moderate stenosis lesion in the right coronary artery (RCA). The fractional flow reserve (FFR) of the RCA was 0.76. After steroid therapy, the mass lesions around the coronary arteries improved. The FFR of the RCA also improved from 0.76 to 0.86. These findings suggest the efficacy of using steroid therapy for coronary artery involvement with IgG4-RD.

Long-Term Prognosis of Patients Who Underwent Percutaneous Transvenous Mitral Commissurotomy for Mitral Stenosis.

The long-term prognosis for up to 20 years of patients who have undergone percutaneous transvenous mitral commissurotomy (PTMC) for mitral stenosis (MS) is unknown.We examined 77 of 93 patients (83%) with MS and who underwent PTMC from 1989 to 2002 at our institute, as well as the occurrence of either one of the following clinical endpoints until September 1, 2018: all-cause death or repeat intervention for the mitral valve.The mean follow-up duration was 20.5 ± 7.3 years. The mean age was 51 ± 11 years. Overall, the 20-year survival rate was 71% ± 5%; without any intervention, the 20-year survival rate was 40% ± 6%. In patients who achieved good immediate results (i.e., mitral valve area (MVA) of ≥ 1.5 cm2 without mitral regurgitation (MR) of > 2/4 after PTMC), the 20-year survival rate was 80% ± 6%; without any intervention, the 20-year survival rate was 54% ± 7%.In our 20-year observational study, patients who have undergone PTMC for MS had favorable prognosis, especially in those who achieved good immediate results. In those who had poor immediate results, careful follow-up is needed because they might have more clinical event and any intervention for the mitral valve.

Pulmonary Artery Sarcoma Diagnosed Using an Endovascular Catheter Forceps Biopsy.

We herein report a case of pulmonary artery sarcoma (PAS) in a 64-year-old woman. She was admitted to our hospital because of massive genital bleeding from endometrial cancer. Contrast-enhanced computed tomography (CT) revealed a left pulmonary artery mass and deep vein thrombosis. She underwent anticoagulant therapy for one year. However, the mass lesion gradually expanded. 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed a positive uptake of FDG by the mass. An endovascular catheter biopsy was performed for the differentiation of endometrial cancer metastasis or primary sarcoma. The biopsy specimen tissue comprised spindle-shaped cells. Thus, the patient was diagnosed with PAS.

Usefulness of Repeat Angiography to Establish Spontaneous Coronary Artery Dissection in Small Vessels.

Background: Spontaneous coronary artery dissection (SCAD) is a rare disease that is often misdiagnosed, except in typical cases. Although intracoronary imaging and multislice coronary computed tomography angiography (CCTA) are useful in establishing dissection, they may not be feasible in all instances, especially in small vessels. Methods and Results: We describe a series of 7 patients with acute coronary syndrome secondary to small vessel SCAD that was detected only upon repeat coronary angiography (CAG). This cohort had a mean (±SD) age of 50±6 years, was predominantly female (n=6; 86%), and had few coronary risk factors. Three patients (43%) had dissection of the distal segment of the right coronary artery, 3 (43%) had distal left circumflex artery dissection, and 1 patient (14%) had a diagonal branch dissection. None of the patients required percutaneous coronary intervention, and received conservative therapy only, because the infarct area was sufficiently small. No definitive diagnosis of SCAD could be established in any of the patients at first admission because CAG alone or CCTA did not reveal the presence of a flap or intraluminal hemorrhage. However, in such patients without a definitive diagnosis, repeat CAG in the chronic stage showed enlargement of vessels, suggesting the healing of an SCAD. Conclusions: Repeat CAG may be useful for suggesting the occurrence of SCAD.

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.

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.

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.

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.

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.

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.

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.

Preservation of renal function in response to cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) has recently been introduced as a new option for patients with severe heart failure, but its effect on renal function remains unclear. METHODS AND RESULTS: Twenty-three patients receiving CRT were studied. Responders were those who showed >0% increase in left ventricular ejection fraction after CRT by echocardiography. Clinical parameters, echocardiographic measurement, renal function, and prescriptions were examined before and 3 months after CRT, and the relationship between the response to CRT and renal function was examined. The responders had a better prognosis than the non-responders (p<0.05). There was a significant difference in the change in the estimated glomerular filtration rate between the responders and non-responders (p<0.05), even in patients with renal dysfunction before CRT (p<0.01). Prescriptions of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB) were 100% in the CRT responders and 60% in the non-responders (p<0.05). Up-titration of beta-blockers could be significantly achieved in the CRT responders compared with the non-responders (p<0.05). CONCLUSIONS: Preservation of renal function was observed in the responders to CRT, even in patients with renal dysfunction. Prescription of ACEI/ARB and up-titration of beta-blockers increased in the CRT responders. These results may contribute to the beneficial effects of CRT.

Comparative analysis of systolic and isolated diastolic dysfunction: Sado heart failure study.

Determining the type of cardiac dysfunction is important for implementing therapeutic strategies and for prognostic insights. We characterized systolic dysfunction (SD) and isolated diastolic dysfunction (IDD) in adults referred for echocardiographic evaluation, and compared their clinical and other characteristics. In the present work, we studied 218 patients (137 males) with cardiac dysfunction (mean age, 66.3 +/- 8.3 years). SD was defined as a left ventricular ejection fraction (LVEF) of < 45%, whereas IDD was defined as a LVEF >or= 45% in addition to the standard Doppler-echocardiography diagnostic criteria for IDD. Approximately 68% of subjects had SD (70% males). The proportions of hypertension, diabetes, and dyslipidemia were 44%, 26%, and 22%, respectively, without significant association with the type of dysfunction. Myocardial infarction (MI) was found in 31% of patients, and was significantly (P < 0.001) more prevalent among SD compared with IDD cases. Cerebral stroke (18%) and malignancy (16%) were significantly associated with IDD (29% versus 13% for SD in the case of stroke, and 26% versus 11% for SD in the case of malignancy; P = 0.008 for each). In multivariately-adjusted logistic regression analysis, the following variables were found to be significantly (P < 0.05) and independently associated with IDD: female gender (odds ratio [OR] = 2.207 [95% CI = 1.302-4.608]), stroke (OR = 2.009 [1.119-3.980]), and malignancy (OR = 2.016 [1.230-4.010]). On the other hand, previous MI (OR = 2.075 [1.769-4.808]) was independently associated with SD. In conclusion, some factors/comorbidities were more likely to associate with IDD (female gender, stroke, and malignancy) or SD (previous MI) when IDD and SD were compared with each other.

Health-related quality of life of outpatients with systolic and isolated diastolic dysfunction: Sado Heart Failure Study.

BACKGROUND: The impact of isolated diastolic dysfunction (IDD) and systolic dysfunction (SD) on health-related quality of life (HRQOL) is unknown. METHODS AND RESULTS: To evaluate HRQOL in patients with IDD and SD under treatment, information on outpatients aged 60-84 years was extracted from the records of 4,500 consecutive individuals who underwent echocardiographic examination at Sado General Hospital. The medical records of these patients were reviewed and a questionnaire, including the Medical Outcome Study Short Form 36, was mailed to 71 IDD and 99 SD patients; answers were obtained from 66 and 91 patients, respectively. The HRQOL of patients with cardiac dysfunction was impaired even when echocardiographic parameters improved with treatment. Patients with IDD showed an impairment of HRQOL similar to those with SD. Compared with males, female patients had a larger and more significant reduction in the physical and mental components of the HRQOL score. These scores correlated positively with exercise capacity in patients with IDD or SD. CONCLUSIONS: Impaired HRQOL, in both its mental and physical components, is a serious problem for IDD and SD patients under treatment. Because exercise intolerance may underlie the reduced HRQOL, improving exercise capacity could be an important target for managing outpatients with heart failure.

Serial electrocardiographic findings in women with Takotsubo cardiomyopathy.

This study aimed to clarify detailed and serial electrocardiographic findings in patients with Takotsubo cardiomyopathy from onset to recovery. Nine consecutive women aged 65 to 84 years (mean 74) with Takotsubo cardiomyopathy were investigated. Standard 12-lead electrocardiograms were recorded during hospitalization and ST-segment elevation and T-wave inversion were manually measured daily in each patient. All 9 patients had 4 phases found electrocardiographically. Phase 1 was characterized by ST-segment elevation immediately after onset. Subsequently, T-wave inversion was observed from days 1 to 3 (phase 2), then inverted T waves improved transiently from days 2 to 6 (phase 3). After this phase, giant inverted T waves with QT prolongation appeared and persisted > or =2 months until recovery (phase 4). Serum creatine kinase levels were increased only at onset. Left ventricular wall motion abnormalities evaluated using echocardiography improved gradually after phase 3 in all patients. Second T-wave inversions (phase 4) were significantly deeper than those of the first one (phase 2; p <0.05). In conclusion, 4 electrocardiographic phases in patients with Takotsubo cardiomyopathy were shown. This observation may be helpful to understand the pathophysiologic process of Takotsubo cardiomyopathy.