Prognostic value of E/e' ratio and its change over time in ST-segment elevation myocardial infarction with preserved left ventricular ejection fraction in the reperfusion era.

BACKGROUND: The ratio of early diastolic mitral inflow velocity to mitral annular velocity (E/e') is a prognostic factor in patients with ST-segment elevation myocardial infarction (STEMI). However, data are lacking on long-term outcomes and longitudinal changes in E/e' in patients with preserved left ventricular ejection fraction (LVEF) in the reperfusion era. METHODS: This is a pre-specified echocardiographic substudy of a randomized controlled trial evaluating the efficacy of beta-blockers in STEMI patients with LVEF ≥40 % after primary percutaneous coronary intervention (PCI). Patients were divided into 2 groups according to E/e' at discharge: ≤14 (normal E/e' group) or > 14 (high E/e' group). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, acute coronary syndrome, and heart failure hospitalization. We also assessed longitudinal changes in E/e' and conducted a landmark analysis using E/e' at 1 year after STEMI. RESULTS: There were 173 and 38 patients in the normal and high E/e' groups, respectively. During a median follow-up of 3.9 years, the primary outcome occurred in 19 patients (11.0 %) and 10 patients (26.3 %) in the normal and high E/e' groups, respectively. The cumulative incidence of the primary outcome was higher in the high E/e' group than in the normal E/e' group (21.9 % vs. 7.1 % at 3 years; log-rank p = 0.013). E/e' in the high E/e' group decreased over time (p < 0.001), but remained higher than in the normal E/e' group at 1 year after STEMI (13.7 ±â€¯5.3 vs. 8.6 ±â€¯2.3, p < 0.001). E/e' > 14 at 1 year was also associated with poor outcomes (log-rank p = 0.008). A sensitivity analysis using multivariate Cox proportional hazards regression models yielded consistent results. CONCLUSION: High E/e' at discharge is associated with poor long-term outcomes in STEMI patients with preserved LVEF after primary PCI, which may be explained by persistent high E/e' late after STEMI.

Safety and Efficacy of NY-ESO-1 Antigen-Specific T-Cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial.

PURPOSE: To determine, for patients with advanced or recurrent synovial sarcoma (SS) not suitable for surgical resection and resistant to anthracycline, the safety and efficacy of the infusion of autologous T lymphocytes expressing NY-ESO-1 antigen-specific T-cell receptor (TCR) gene and siRNA to inhibit the expression of endogenous TCR (product code: TBI-1301). PATIENTS AND METHODS: Eligible Japanese patients (HLA-A*02:01 or *02:06, NY-ESO-1-positive tumor expression) received cyclophosphamide 750 mg/m2 on days -3 and -2 (induction period) followed by a single dose of 5×109 (±30%) TBI-1301 cells as a divided infusion on days 0 and 1 (treatment period). Primary endpoints were safety-related (phase I) and efficacy-related [objective response rate (ORR) by RECIST v1.1/immune-related RECIST (irRECIST); phase II]. Safety- and efficacy-related secondary endpoints were considered in both phase I/II parts. RESULTS: For the full analysis set (N = 8; phase I, n = 3; phase II, n = 5), the ORR was 50.0% (95% confidence interval, 15.7-84.3) with best overall partial response in four of eight patients according to RECIST v1.1/irRECIST. All patients experienced adverse events and seven of eight patients (87.5%) had adverse drug reactions, but no deaths were attributed to adverse events. Cytokine release syndrome occurred in four of eight patients (50.0%), but all cases recovered with prespecified treatment. Immune effector cell-associated neurotoxicity syndrome, replication-competent retrovirus, and lymphocyte clonality were absent. CONCLUSIONS: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1-positive tumor cells appears to be a promising strategy for the treatment of advanced or recurrent SS with acceptable toxicity.

Solution-Processable Colorless Polyimides Derived from Hydrogenated Pyromellitic Dianhydride: Strategies to Reduce the Coefficients of Thermal Expansion by Maximizing the Spontaneous Chain Orientation Behavior during Solution Casting.

In this study, practically useful colorless polyimides (PIs) with low coefficients of thermal expansion (CTEs) and other desirable properties were prepared from hydrogenated pyromellitic dianhydride (1-exo,2-exo,4-exo,5-exo-cyclohexanetetracarboxylic dianhydride, H-PMDA). A modified one-pot polymerization method afforded a high-molecular-weight PI with sufficient film-forming ability from 2,2'-bis(trifluoromethyl)benzidine (TFMB) with a rod-like structure and H-PMDA. However, the PI film cast from its homogeneous solution did not have low CTEs, similar to the analogous system using meta-tolidine. To solve this problem, a series of amide- and amide-imide-containing diamines were designed and synthesized. The modified one-pot polymerization of H-PMDA and the diamines in γ-butyrolactone produced homogeneous, viscous, and stable solutions of high-molecular-weight PIs with high solid contents. The cast films of certain systems examined in this study simultaneously achieved low CTEs, high optical transparency, considerably high glass transition temperatures (Tgs), and sufficient ductility. A possible mechanism for the generation of low CTEs, which is closely related to the spontaneous in-plane orientation behavior during solution casting, was proposed. Certain H-PMDA-based PIs developed in this study are promising colorless heat-resistant plastic substrates for use in image display devices and other optical applications.

[Signs can be Found in "Clinical Laboratory Values" and "Ultrasonographic Findings" -Chairmen's Introductory Remarks.]

Many examinations have limitations, including specificity. Therefore, multiple examinations should be combined for practical diagnosis to facilitate treatment. In symposium 14 (ultrasound and clinical examina- tion), 5 speakers presented how to combine diagnostic methods in their clinical practice. This symposium highlighted the importance of the comprehensive management of multiple examinations for optimal patient care.

Effects of medical treatment on the prognosis and risk of embolic events in patients with severe aortic plaque.

AIM: The optimal treatment strategy for patients with aortic atheroma is not well established because data regarding medical treatment for such patients are lacking, especially with respect to the Japanese population. The purpose of this study was to clarify the effects of medical treatment on the risk of embolic events and mortality in patients with severe aortic plaque. METHODS: We retrospectively investigated 75 consecutive patients with severe aortic plaque detected on transesophageal echocardiography (TEE) between 1995 and 2005. The occurrence of embolic events and all-cause death in the period after TEE was assessed. The cumulative incidence of subsequent embolic events and death was evaluated in relation to specific medical treatments, including statins, antiplatelet drugs and warfarin. RESULTS: Embolic events occurred in 27 patients (36%) and death occurred in 37 patients (49%) during follow-up (5.6±3.0 years). The patients who experienced embolic events had a significantly higher prevalence of previous embolic events, atrial fibrillation and hemodialysis than the patients who did not experience embolic events. Univariate and multivariate analyses showed that the use of statins and/or antiplatelet drugs was significantly associated with a low incidence of death but not with a low incidence of embolic events. On the other hand, warfarin exhibited neither beneficial nor harmful effects on the incidence of embolic events or death. CONCLUSIONS: Statin and antiplatelet drugs have beneficial effects on the prognosis of patients with severe aortic plaque diagnosed on TEE.

Usefulness of real-time three-dimensional echocardiography in evaluating aortic root diameters during a cardiac cycle.

BACKGROUND: The preoperative evaluation of aortic root diameters is important for determining the surgical strategy in patients with aortic valve disease. The purpose of this study was to evaluate the usefulness of real-time three-dimensional echocardiography (3D-echo) for the evaluation of aortic root diameters compared with two-dimensional echocardiography (2D-echo) and to evaluate aortic root dynamics. METHODS: We prospectively investigated 23 patients with aortic stenosis (AS) and 37 normal controls. With 2D-echo, aortic root diameters were measured from the parasternal long-axis view. With 3D-echo, long-axis and short-axis views of the aortic root were reconstructed from the full-volume image, and aortic root diameters were measured at mid-systole, end-systole, mid-diastole, and end-diastole. These aortic root diameters were compared between 2D and 3D measurements, regarding intraoperative and computed tomographic measurements as the gold standard. In addition, dynamic changes of aortic root diameters during a cardiac cycle were evaluated. RESULTS: Aortic root diameters measured by 3D-echo were larger than those measured by 2D-echo (annular diameter 19.6 ± 2.1 vs. 21.2 ± 2.2 mm, p < 0.0001), and 3D measurements were closer to intraoperative and computed tomographic measurements than 2D measurements. The diameter of the aortic annulus increased during diastole, but the changes during a cardiac cycle were significantly smaller in patients with AS than in normal controls (2.0 ± 2.2 vs. 7.8 ± 3.4%, p < 0.0001). CONCLUSIONS: Aortic root diameters can be more accurately measured by 3D-echo than 2D-echo. Dynamic change of the aortic annulus during a cardiac cycle was smaller in patients with AS. 3D-echo is useful for the quantitative evaluation of the aortic root, including dynamics during a cardiac cycle.

A case of significantly increased mitral regurgitation early after atrial septal defect closure.

We report a rare case in which mitral regurgitation (MR) was exacerbated to a severe level early after atrial septal defect (ASD) closure, even though the female patient had preoperatively mild MR and mild changes in mitral valve (MV) and sinus rhythm. The mechanism of increased MR was considered as poor coaptation and tethering of the MV due to the restricted motion of the posterior leaflet in addition to geometric changes of the left ventricle (LV) after ASD closure.

Progression of isolated tricuspid regurgitation late after left-sided valve surgery. Clinical features and mechanisms.

BACKGROUND: Severe tricuspid regurgitation (TR) sometimes develops late after left-sided valve surgery without left heart failure, pulmonary hypertension or rheumatic tricuspid valve. The purpose of the present study was to investigate clinical characteristics and mechanisms of severe isolated TR late after left-sided valve surgery. METHODS AND RESULTS: A total of 372 consecutive patients who underwent left-sided valve surgery between 1990 and 2003 and who were followed up with echocardiography for at least 5 years, were retrospectively investigated. The mean follow-up period was 9.4 years. Clinical background, preoperative and postoperative echocardiographic parameters were evaluated. Among the 372 patients, severe isolated TR was detected in 23 patients, which developed at a mean of 8.6 years after surgery. Twenty-two of 23 patients had undergone mitral valve surgery. Multivariate logistic regression analysis identified the presence of preoperative atrial fibrillation and preoperative ejection fraction as independent determinants for the development of severe isolated TR. In patients with severe isolated TR, the tricuspid annular diameter and the right atrial area were already enlarged early after surgery and both of these increased prior to TR progression. CONCLUSIONS: Severe isolated TR developing late after mitral valve surgery is not uncommon, thus it is important to recognize this disease entity. Annular dilatation was the main cause of isolated TR and serial echocardiographic data are important to detect progression of isolated TR and to assess its mechanisms.

Marked regression of aortic plaque by intensive cholesterol-lowering therapy.

A 65-year-old man with rheumatic combined valvular heart disease showed a persistent fever after cardiac catheterization. He was diagnosed with cholesterol embolism due to multiple mobile plaques in the descending thoracic aorta by transesophageal echocardiography (TEE) along with persistent eosinophilia, deteriorating renal function, and blue toe sign. He was treated with intensive cholesterol-lowering therapy for 3 years, resulting in marked regression of the aortic plaque on TEE.

Evaluation of left ventricular rotation by two-dimensional speckle tracking method and real-time three-dimensional echocardiography: comparison with MRI tagging method.

BACKGROUND: Recently, it has become possible to evaluate left ventricular (LV) torsion by two-dimensional (2D) speckle tracking images. However, LV torsion is a three-dimensional (3D) performance, which per se cannot be assessed by the 2D speckle tracking method. The present study investigated the accuracy of the 2D speckle tracking method and real-time 3D echocardiography in measuring LV rotation, comparing with the MRI tagging method. METHODS: We assessed LV apical rotation using the 2D speckle tracking method, real-time 3D echocardiography, and MRI tagging method in 26 normal subjects, and compared the results of these three methods. LV apical rotation was measured just before the level in which the posterior papillary muscle was absorbed into the free wall. RESULTS: The degree of LV apical rotation evaluated by the 2D speckle tracking method (Δθ 2D) was significantly smaller than that evaluated by 3D echocardiography (Δθ 3D) and the MRI tagging method (Δθ MRI) (Δθ 2D 7.3 ± 2.8°; Δθ 3D 8.8 ± 3.4°; Δθ MRI 9.0 ± 3.4°; Δθ 2D vs. Δθ 3D, p = 0.0001; Δθ 2D vs. Δθ MRI, p < 0.0001). There were good correlations among Δθ 2D, Δθ 3D, and Δθ MRI, but agreement between Δθ 3D and Δθ MRI (mean difference 0.14 ± 1.43°) was better than that between Δθ 2D and Δθ MRI (mean difference 1.68 ± 1.89°). CONCLUSION: The degree of LV apical rotation was underestimated with the 2D speckle tracking method compared with the MRI tagging method, whereas it could be precisely measured by 3D echocardiography.

Impact of aortic plaque morphology on survival rate and incidence of a subsequent embolic event ­ long-term follow-up data ­.

BACKGROUND: There are no reports about the long-term follow-up data of patients with aortic plaques among the Japanese population. The purpose of this study was to clarify the frequency of patients with severe aortic plaques and the impact of aortic plaque morphology on the prognosis. METHODS AND RESULTS: We retrospectively investigated 1,570 consecutive patients who underwent transesophageal echocardiography. Survival rate and subsequent embolic event rate were compared between patients with severe aortic plaque (>5 mm in thickness) and control patients. The relationship between aortic plaque morphology and prognosis was also estimated according to the presence of ulceration, calcification, hypoechoic plaques, and mobile plaques. The mean follow-up period was 8.7 years. Among 1,570 patients, severe aortic plaque was detected in 92 patients (5.9%). These 92 patients showed a significantly low survival rate and high subsequent embolic event rate compared to control patients (5-year survival rate: 69% vs 94%; 5-year embolic event free rate: 52% vs 95%). Among patients with severe aortic plaque, only ulceration was associated with a low survival rate (hazards ratio: 2.4, 95% confidence interval (CI): 1.1-5.2) and only mobile plaque was associated with a high embolic event rate (hazards ratio: 2.2; 95%CI: 1.1-5.1). CONCLUSIONS: Aortic plaque >5 mm in thickness was a predictor of poor prognosis. In the presence of aortic plaque >5 mm, ulceration was a predictor of a low survival rate and mobile plaque was a predictor of a high embolic event rate.

Cardiac tamponade during transesophageal echocardiography in a patient with infective endocarditis.

An 81-year-old man with a history of diabetes mellitus and end-stage renal disease was admitted because of infective endocarditis. During transesophageal echocardiography (TEE), pericardial effusion rapidly increased and led to cardiac tamponade. Despite intensive therapy, the patient did not recover. Autopsy showed hemopericardium, ruptured sinus of Valsalva, and vegetation on the aortic valve. Our case suggests that cardiac tamponade due to the rupture of a sinus of Valsalva can occur in patients with aortic valve endocarditis complicated by perivalvular abscess. Therefore, we must be aware of this devastating complication and take preventive measures when performing TEE in such patients.

Usefulness of contrast echocardiography for detecting right-to-left cardiac shunts during the diagnosis of hypoxemia: 2 case reports.

We report two cases in which contrast echocardiography was useful for detecting right-to-left shunt. In case 1, a 53-year-old man was admitted to our hospital after being diagnosed with acute heart failure. Even after improvement of the heart failure, hypoxemia remained. Contrast echocardiography was performed. When contrast medium was injected into the left antecubital vein, it directly drained into the left atrium. When contrast medium was injected into the right antecubital vein, it drained into the right atrium not the left atrium. These findings proved the existence of a right-to-left shunt. In case 2, a 68-year-old man felt dyspnea on mild effort, especially when sitting in an anteflexing posture. In room air, his SpO2 was 95% when sitting in a resting posture and 79% when in an anteflexing sitting posture. Contrast echocardiography was performed. A patent foramen ovale (PFO) was proved using the Valsalva maneuver, and the contrast medium drained from right atrium into the left atrium via the PFO. He underwent patch closure of the PFO, and his symptoms disappeared. Contrast echocardiography should be performed for the diagnosis of chronic hypoxemia for which causes are not detected with routine clinical examinations, in order to confirm right-to-left shunt.

Cholesterol embolism after cardiac catheterization mimicking infective endocarditis.

We present a 65-year-old man with rheumatic combined valvular heart disease showing persistent fever 3 weeks after diagnostic cardiac catheterization. Infective endocarditis was strongly suspected from the clinical course, however, serial blood cultures were negative. Transesophageal echocardiography, done to investigate vegetation, revealed multiple mobile plaques in the descending aorta. Administration of both steroid and simvastatin improved both symptoms and renal function. Cholesterol embolism should be considered to be one of the possible causes of low-grade fever after cardiac catheterization especially in patients with anticoagulation.

[Efficacy of transesophageal echocardiography in patients with cardiac arrest or shock].

OBJECTIVES: Only a few examinations are available to critically ill patients. We assessed the efficacy of transesophageal echocardiography (TEE) in the management of patients with cardiac arrest or shock. METHODS: Among a total of 2,021 patients who underwent TEE over the past 13 years at our institution, we reviewed 18 patients who underwent TEE during cardiac arrest or shock. RESULTS: TEE was performed in four patients with cardiac arrest and in 14 patients with shock. In 12 (67%) of 18 patients, TEE identified the following abnormalities: aortic dissection in four, ruptured thoracic aortic aneurysm in two, papillary muscle rupture in two, left ventricular free wall rupture in two, postoperative cardiac tamponade in one and ruptured chordae tendineae in one. TEE excluded suspected cardiac abnormality in two other patients. Transthoracic echocardiography could not be performed in 8 of 18 patients, and showed poor quality of images in the remaining 10 patients. Of the 12 patients with a diagnosis based on TEE, three patients died during cardiopulmonary resuscitation, whereas nine patients were treated with emergent surgery and six of these survived to hospital discharge. CONCLUSIONS: TEE is feasible even in patients with cardiac arrest or shock, and can play an important role in establishing the diagnosis and determining the treatment of such patients.

Usefulness of high-frequency transthoracic Doppler echocardiography in noninvasive diagnosis of the left internal thoracic artery graft stenosis at the anastomosis.

BACKGROUND: Stenosis of the left internal thoracic artery (LITA) graft, which usually occurs at the site of the anastomosis, can be noninvasively evaluated by the flow pattern in the proximal graft, but the flow pattern is influenced by several other factors. METHODS AND RESULTS: In the present study, LITA graft flow was investigated by high-frequency transthoracic Doppler echocardiography in 75 consecutive patients who underwent postoperative angiography of the LITA graft. The flow velocity was measured at both the anastomosis and proximal to it, and compared with the quantitative angiographic results. Flow at both sites was detected in 61 (81%) of the 75 patients. The diastolic velocity ratio of the anastomosis to the proximal site correlated with the percent diameter stenosis at the anastomosis. A diastolic velocity ratio >2.0 had a high sensitivity, specificity, positive predictive value and negative predictive value for the presence of significant stenosis at the anastomosis of a LITA graft. CONCLUSIONS: High-frequency transthoracic Doppler echocardiography can be used for the noninvasive diagnosis of LITA graft stenosis.

Analysis of clinical background in patients with vegetation-like echoes: importance of clinical information.

PURPOSE: Detection of vegetation is important for diagnosing infective endocarditis. METHODS: We analyzed clinical information from 58 patients with vegetation-like echoes on transthoracic echocardiography who had been referred to this institution for an echocardiographic examination during the past 5 years. Patients with healed vegetations were excluded. A vegetation-like echo was defined as a mass, a thread-like echo attached to the valve or endocardium, or both. Diagnosis of a vegetation-like echo required the concurrence of two cardiologists and one sonographer. Altogether, 44 patients were treated with antibiotics because their clinical courses were consistent with active infective endocarditis. RESULTS: Blood cultures were positive in 27 patients and negative in 17 patients. Follow-up data were available for 10 of the 14 patients who had no findings suggestive of active infective endocarditis. The size of the vegetation-like echo remained unchanged over a mean interval of 12.1 months, and no clinical signs or symptoms of active infective endocarditis appeared. In about one-fourth of the patients with a vegetation-like echo, it was not associated with infective endocarditis. CONCLUSION: Clinical information, in addition to detection of a vegetation-like echo, appears to be indispensable for diagnosing infective endocarditis.

Usefulness of the transgastric view by transesophageal echocardiography in evaluating thickened pericardium in patients with constrictive pericarditis.

Detection of thickened pericardium in patients with constrictive pericarditis is essential for pericardiectomy because restrictive cardiomyopathy and severe tricuspid regurgitation show similar hemodynamic data. The purpose of this study was to clarify whether transesophageal echocardiography can evaluate thickened pericardium. We investigated 7 patients with constrictive pericarditis who underwent pericardiectomy. Thickened pericardium over the right atrium was detected in 6 patients, but the borders were not clear. Thickened pericardium over the left ventricle was not detected in any patients in the standard longitudinal and horizontal views. On the other hand, thickened pericardium over the ventricles was detected in all patients in the transgastric view as an echogenic area between the liver and ventricular wall. Tissue characteristics of the thickened pericardium could be evaluated because of the high-quality images in the transgastric view. The transgastric view by transesophageal echocardiography allows high-quality images of the pericardium, which might be useful in diagnosing constrictive pericarditis.

Roles of the central prostaglandin EP3 receptors in cardiovascular regulation in rats.

In this study, we examined the effects of an intracerebroventricular (i.c.v.) administration of prostaglandin E2 (PGE2) and of selective agonists for PGE2 receptor subtypes, EP1, EP2, EP3 and EP4, on central cardiovascular regulation and renal sympathetic nerve activity (RSNA) in urethane-anesthetized rats. The central administration of PGE2 (0.01-1.0 nmol) resulted in increases in blood pressure, heart rate (HR) and RSNA in a dose-dependent manner. Cardiovascular responses to PGE2 (0.5 nmol, i.c.v.) were attenuated by pretreatment with ganglionic and adrenoceptor blocking agents, but not with SC-19220 (20 nmol, i.c.v.), an EP1 receptor antagonist. An i.c.v. administration of the EP3 agonist ONO-AE-248 (50.0 nmol) resulted in an increase in RSNA with pressor and tachycardia responses, while administration of the EP2 agonist ONO-AE1-259 and the EP4 agonist ONO-AE1-329 caused transient hypotension and slight increases in HR and RSNA. The administration of the selective EP1 agonist ONO-DI-004 showed no effect. These results suggest that the central PGE2-induced activation of the sympathetic nerve activity with hypertension and tachycardia may depend on stimulation of the EP3 receptors in the central nervous system.