Transthoracic echocardiography monitoring during ASD closure using an artificial hand system.

AIM: Continuous real-time echocardiographic monitoring is essential for guidance during ASD closure. However, transthoracic echocardiography (TTE) can only be implemented intermittently during fluoroscopy. We evaluate a novel approach to provide real-time imaging during the entire procedure. FINDING: We developed a custom-made TTE monitoring apparatus using artificial hand (AH-TTE) that enables real-time TTE images during atrial septal defect (ASD) closure. Thirty-two patients underwent successful device implantation using AH-TTE monitoring without complications. The median duration for real-time AH-TTE monitoring was 22 min and the median fluoroscopy time was 7.2 min. One case of pericardial effusion and one of transient bradycardia event due to air embolism was detected. All patients had uneventful recoveries. CONCLUSIONS: Our simple and novel monitoring technique with AH-TTE provides TEE-like monitoring and may be a new alternative method for ASD closure. It gives real-time stable TTE images and minimizes radiation exposure for the interventional team during fluoroscopy.

Exogenous GDF11 attenuates non-canonical TGF-ß signaling to protect the heart from acute myocardial ischemia-reperfusion injury.

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor beta 1 (TGF-ß1) superfamily that reverses age-related cardiac hypertrophy, improves muscle regeneration and angiogenesis, and maintains progenitor cells in injured tissue. Recently, targeted myocardial delivery of the GDF11 gene in aged mice was found to reduce heart failure and enhance the proliferation of cardiac progenitor cells after myocardial ischemia-reperfusion (I-R). No investigations have as yet explored the cardioprotective effect of exogenous recombinant GDF11 in acute I-R injury, despite the convenience of its clinical application. We sought to determine whether exogenous recombinant GDF11 protects against acute myocardial I-R injury and investigate the underlying mechanism in Sprague-Dawley rats. We found that GDF11 reduced arrhythmia severity and successfully attenuated myocardial infarction; GDF11 also increased cardiac function after I-R, enhanced HO-1 expression and decreased oxidative damage. GDF11 activated the canonical TGF-ß signaling pathway and inactivated the non-canonical pathways, ERK and JNK signaling pathways. Moreover, administration of GDF11 prior to reperfusion protected the heart from reperfusion damage. Notably, pretreatment with the activin-binding protein, follistatin (FST), inhibited the cardioprotective effects of GDF11 by blocking its activation of Smad2/3 signaling and its inactivation of detrimental TGF-ß signaling. Our data suggest that exogenous GDF11 has cardioprotective effects and may have morphologic and functional recovery in the early stage of myocardial I-R injury. GDF11 may be an innovative therapeutic approach for reducing myocardial I-R injury.

Tailored Holder for Continuous Echocardiographic Monitoring.

Hemodynamic monitoring is essential for prompt and effective interventions in intensive care unit patients. We developed a custom-made transthoracic echocardiography transducer holder consisting of transducer holder and skin patch attachment. This holder allowed continuous transthoracic echocardiography monitoring in 5 adult patients with circulatory failure due to shock, and 6 pediatric patients after successful percutaneous closure of a ventricular septal defect. One case of an unexpected hemopericardium was promptly diagnosed and pericardiocentesis was performed, and 1 patient required extracorporeal membrane oxygenation support.

Transcatheter Closure of Atrial Septal Defect with Attenuated Anterior Rim after Transcatheter Aortic Valve Implantation: Can It Be Carried out as a Single Procedure?

Transcatheter aortic valve replacement (TAVR) has emerged as a highly effective minimally invasive treatment for symptomatically critical aortic stenosis (AS) in patients at high or prohibitive surgical risk. We report a case of staged transcatheter management of critical AS combined with an atrial septal defect (ASD) with attenuated anterior superior rim. The clinical result of this case suggests that both procedures can be safely performed simultaneously. Therefore, combined transcatheter treatment may appear as a possible strategy in patients with concomitant cardiac conditions.

The role of adenosine in preconditioning by brief pressure overload in rats.

BACKGROUND/PURPOSE: Brief pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits has been previously reported. Its effects in other species are not known. This study investigates effects of pressure overload and the role of adenosine in rats in this study. METHODS: MI was induced by 40-minute occlusion of the left anterior descending coronary artery followed by 3-hour reperfusion. MI size was determined by triphenyl tetrazolium chloride staining. Brief pressure overload was induced by two 10-minute episodes of partial snaring of the ascending aorta. Systolic left ventricular pressure was raised 50% above the baseline value. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions. RESULTS: The MI size (mean ± standard deviation), expressed as percentage of area at risk, was significantly reduced in the pressure overload group as well as in the ischemic preconditioning group (17.4 ± 3.0% and 18.2 ± 1.5% vs. 26.6 ± 2.4% in the control group, p < 0.001). Pretreatment with 8-(p-sulfophenyl)-theophylline (SPT), an inhibitor of adenosine receptors, did not significantly limit the protection by pressure overload and ischemic preconditioning (18.3 ± 1.5% and 18.2 ± 2.0%, respectively, p < 0.001). SPT itself did not affect the extent of infarct (25.4 ± 2.0%). The hemodynamics, area at risk and mortality were not significantly different among all groups of animals. CONCLUSION: Brief pressure overload of the left ventricle preconditioned rat myocardium against infarction. Because SPT did not significantly alter MI size reduction, our results did not support a role of adenosine in preconditioning by pressure overload in rats.

Transcatheter Aortic Valve Implantation in a Woman with Porcelain Aorta, Previous Sternotomy for Coronary Artery Bypass Grafting, and Critical Aortic Stenosis.

UNLABELLED: A 74-year-old woman who was diagnosed with right breast cancer at age 39 had been treated with mastectomy, and repeated cycles of chemotherapy and radiotherapy. She also had a history of coronary artery disease, wherein two coronary artery bypass grafts were performed 3 years ago. At that time, porcelain aorta was detected during surgery. In the year prior to admission, the patient presented with severe symptomatic critical aortic stenosis. Due to the prohibitively high surgical risk and need for aortic valve replacement, she underwent successful transcatheter aortic valve implantation with transfemoral implantation of a 29 mm Medtronic CoreValve prosthesis. The patient experienced a good result with reduction of the transaortic gradient and mild residual aortic regurgitation. KEY WORDS: Aortic stenosis; Coronary artery bypass grafting; Porcelain aorta; Radiation; Transcatheter aortic valve implantation.

Quantitative analysis of mitral valve morphology in mitral valve prolapse with real-time 3-dimensional echocardiography: importance of annular saddle shape in the pathogenesis of mitral regurgitation.

BACKGROUND: Few data exist on the relation of the 3-dimensional morphology of mitral valve and degree of mitral regurgitation (MR) in mitral valve prolapse. METHODS AND RESULTS: Real-time 3-dimensional transesophageal echocardiography of the mitral valve was acquired in 112 subjects, including 36 patients with mitral valve prolapse and significant MR (≥3+; MR+ group), 32 patients with mitral valve prolapse but no or mild MR (≤2+; MR- group), 12 patients with significant MR resulting from nonprolapse pathologies (nonprolapse group), and 32 control subjects. The 3-dimensional geometry of mitral valve apparatus was measured with dedicated quantification software. Compared with the normal and MR- groups, the MR+ group had more dilated mitral annulus (P<0.0001), a reduced annular height to commissural width ratio (AHCWR) (P<0.0001) indicating flattening of annular saddle shape, redundant leaflet surfaces (P<0.0001), greater leaflet billow volume (P<0.0001) and billow height (P<0.0001), longer lengths from papillary muscles to coaptation (P<0.0001), and more frequent chordal rupture (P<0.0001). Prevalence of chordal rupture increased progressively with annulus flattening (7% versus 24% versus 42% for AHCWR >20%, 15%-20%, and <15%, respectively; P=0.004). Leaflet billow volume increased exponentially with decreasing AHCWR in patients without chordal rupture (r(2)=0.66, P<0.0001). MR severity correlated strongly with leaflet billow volume (r(2)=0.74, P<0.0001) and inversely with AHCWR (r(2)=0.44, P<0.0001). In contrast, annulus dilatation but not flattening occurred in nonprolapse MR patients. An AHCWR <15% (odds ratio=7.1; P=0.0004) was strongly associated with significant MR in mitral valve prolapse. CONCLUSION: Flattening of the annular saddle shape is associated with progressive leaflet billowing and increased frequencies of chordal rupture and may be important in the pathogenesis of MR in mitral valve prolapse.

Recovery of neurological function of ischemic stroke by application of conditioned medium of bone marrow mesenchymal stem cells derived from normal and cerebral ischemia rats.

BACKGROUND: Several lines of evidence have demonstrated that bone marrow-derived mesenchymal stem cells (BM-MSC) release bioactive factors and provide neuroprotection for CNS injury. However, it remains elusive whether BM-MSC derived from healthy donors or stroke patients provides equal therapeutic potential. The present work aims to characterize BM-MSC prepared from normal healthy rats (NormBM-MSC) and cerebral ischemia rats (IschBM-MSC), and examine the effects of their conditioned medium (Cm) on ischemic stroke animal model. RESULTS: Isolated NormBM-MSC or IschBM-MSC formed fibroblastic like morphology and expressed CD29, CD90 and CD44 but failed to express the hematopoietic marker CD34. The number of colony formation of BM-MSC was more abundant in IschBM-MSC than in NormBM-MSC. This is in contrast to the amount of Ficoll-fractionated mononuclear cells from normal donor and ischemic rats. The effect of cm of BM-MSC was further examined in cultures and in middle cerebral artery occlusion (MCAo) animal model. Both NormBM-MSC Cm and IschBM-MSC Cm effectively increased neuronal connection and survival in mixed neuron-glial cultures. In vivo, intravenous infusion of NormBM-MSC Cm and IschBM-MSC Cm after stroke onset remarkably improved functional recovery. Furthermore, NormBM-MSC Cm and IschBM-MSC Cm increased neurogenesis and attenuated microglia/ macrophage infiltration in MCAo rat brains. CONCLUSIONS: Our data suggest equal effectiveness of BM-MSC Cm derived from ischemic animals or from a normal population. Our results thus revealed the potential of BM-MSC Cm on treatment of ischemic stroke.

Transcatheter intervention for complex ascending aortic pseudoaneurysm after cardiac surgery.

BACKGROUND: Ascending aortic pseudoaneurysm (PsA) is an uncommon but surgically challenging problem with high morbidity and mortality. Herein we describe the efficacy and safety of the different approaches to transcatheter intervention for repair of ascending PsA and assess the selection of occluder devices using real-time 3-dimensional (RT 3D) color Doppler transesophageal echocardiography (TEE).METHODS AND RESULTS: Three patients with complex ascending PsA after cardiac or aortic root surgery were treated with transcatheter intervention due to high risk for redo surgery. Perioperative RT 3D-TEE combined with fluoroscopy was used for monitoring. All ascending PsA were successfully occluded with different devices using the transcatheter technique either with the transapical, transarterial approach, or transvenous combined with hybrid process depending on lesion anatomy. CONCLUSIONS: Treatment of complex ascending PsA with transcatheter or combined hybrid intervention with cautious planning based on patient presentation and well-coordinated teamwork was successful. RT 3D color Doppler TEE provided precise information for the selection of appropriate occluder device, and also facilitated the procedure by guiding the catheter through difficult anatomy.

Transcatheter Repair of Iatrogenic Aortic Perforation Complicating Transseptal Puncture for a Catheter Ablation of Atrial Arrhythmia.

UNLABELLED: Aortic root perforation is a potentially life-threatening complication that may occur during transseptal puncture and requires immediate repair. We present a 71-year-old man who was admitted for catheter ablation of persistent atypical atrial flutter. Fluoroscopic-guided transseptal puncture was performed to gain access to the left atrium. An unrecognized puncture of the aortic root by Brockenbrough needle and inadvertent advancement of Mullins sheath resulted in aortic root perforation. We decided to seal the hole transcatheterly with an occluder device. Severe aortic regurgitation (AR) was noted by transesophageal echocardiography after deployment of a 6 mm Amplatzer septal occluder (ASO). Thereafter, we switched to a 6/4-mm Amplatzer duct occluder (ADO) and only minimal AR was noted after deployment. This is because the diameter of the left atrial disc of ASO is larger than the diameter of the retention skirt of ADO to interfere with the movement of aortic valve leaflet. During 6 months of echocardiographic follow-up, the ADO remained in place and no residual shunt was observed. KEY WORDS: Aortic perforation; Transcatheter repair; Transseptal puncture.

Live/Real time three-dimensional transesophageal echocardiography in percutaneous closure of atrial septal defects.

OBJECTIVES: This study assessed the ability of live/real time three-dimensional transesophageal echocardiography (3DTEE) in measuring (1) atrial septal defect (ASD) maximum dimension, area, and adjacent rim size, (2) ASD occluder left and right atrial disk size, (3) length of contact between the left atrial (LA) disk and the aorta, and in (4) assessing device related complications such as residual shunt, device embolization, and device encroachment upon adjacent cardiac structures. MATERIALS AND METHODS: 3DTEE images acquired during percutaneous ASD closure by the Amplatzer Septal Occluder in 15 adult patients were retrospectively analyzed. Offline analysis was done using both the Philips 5500 ultrasound system and Philips QLAB software. 3D color flow Doppler images were used to assess residual ASD shunting. RESULTS: The Philips 5500 and Philips QLAB measurements correlated well for ASD maximum dimension and area measurements. The Philips QLAB 3DTEE disk size measurements also correlated well with the manufacturer obtained sizes. The aortic rim was deficient in 7 of the 15 patients, and the mean ASD occluder device size was 4 mm greater than the mean ASD maximum dimension. The LA occluder disk was in contact with the aorta throughout the cardiac cycle in 12 of the 15 patients, and the LA occluder disk size correlated significantly with the contact length with the aorta. CONCLUSION: Most of the patients demonstrated contact between the LA occluder disk and the aorta throughout the cardiac cycle. 3DTEE may be useful in identifying patients at greater risk for aortic erosion.

Atrial septal occluder device embolization to an iliac artery: a case highlighting the utility of three-dimensional transesophageal echocardiography during percutaneous closure.

Percutaneous closure of secundum atrial defects has become an accepted treatment in part because it is minimally invasive and relatively low risk. Despite recent advances in implantation technique and device improvements, complications occur. Here, we report a case of device embolization during percutaneous repair of an atrial septal defect (ASD) with multiple fenestrations. We highlight the value of using live/real time three-dimensional transesophageal echocardiography to help plan the percutaneous procedure and detect complications.

Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of aortic aneurysm and dissection.

We compared findings from intraoperative live/real time three-dimensional transesophageal echocardiography (3DTEE) and two-dimensional transesophageal echocardiography (2DTEE) with surgery in 67 patients having aortic aneurysm and/or aortic dissection. Of these, 20 patients had aortic aneurysm without dissection, 21 aortic aneurysm and dissection, and 26 aortic dissection without aneurysm. 3DTEE diagnosed the type and location of aneurysm correctly in all patients unlike 2DTEE, which missed an aneurysm in one case. There were four cases of aortic aneurysm rupture. Three of them were diagnosed by 3DTEE but only one by 2DTEE, and one missed by both techniques. The mouth of saccular aneurysm, site of aortic aneurysm rupture, and communication sites between perfusing and nonperfusing lumens of aortic dissection could be viewed en face only with 3DTEE, enabling comprehensive measurements of their area and dimensions as well as increasing the confidence level of their diagnosis. In all patients with aortic dissection, 3DTEE enabled a more confident diagnosis of dissection because the dissection flap when viewed en face presented as a sheet of tissue rather than a linear echo seen on 2DTEE which can be confused with an artifact. 2DTEE missed dissection in one patient. In six cases the dissection flap involved the right coronary artery orifice by 3DTEE and surgery. These were missed by 2DTEE. Aortic regurgitation severity was more comprehensively assessed by 3DTEE than 2DTEE. Aneurysm size by 3DTEE correlated well with 2DTEE and surgery/computed tomography scan. In conclusion, 3DTEE provides incremental information over 2DTEE in patients with aortic aneurysm and dissection.

Inhibition of phosphorylated STAT3 by cucurbitacin I enhances chemoradiosensitivity in medulloblastoma-derived cancer stem cells.

INTRODUCTION: CD133 (PROM1) is a potential marker for cancer stem cells (CSCs), including those found in brain tumors. Recently, medulloblastoma (MB)-derived CD133-positive cells were found to have CSC-like properties and were proposed to be important contributors to tumorigenicity, cancer progression, and chemoradioresistance. However, the biomolecular pathways and therapeutic targets specific to MB-derived CSCs remain unresolved. MATERIALS AND METHODS: In the present study, we isolated CD133(+) cells from MB cell lines and determined that they showed increased tumorigenicity, radioresistance, and higher expression of both embryonic stem cell-related and drug resistance-related genes compared to CD133(-) cells. Bioinformatics analysis suggested that the STAT3 pathway might be important in MB and CD133(+) cells. To evaluate the effects of inhibiting the STAT3 pathway, MB-derived CD133(+/-) cells were treated with the potent STAT3 inhibitor, cucurbitacin I. Treatment with cucurbitacin I significantly suppressed the CSC-like properties and stemness gene signature of MB-derived CD133(+) cells. Furthermore, cucurbitacin I treatment increased the apoptotic sensitivity of MB-derived CD133(+) cells to radiation and chemotherapeutic drugs. Notably, cucurbitacin I demonstrated synergistic effects with ionizing radiation to inhibit tumorigenicity in MB-CD133(+)-inoculated mice. RESULTS: These results indicate that the STAT3 pathway plays a key role in mediating CSC properties in MB-derived CD133(+) cells. Targeting STAT3 with cucurbitacin I may therefore represent a novel therapeutic approach for treating malignant brain tumors.

Cardioprotective effects of luteolin during ischemia-reperfusion injury in rats.

BACKGROUND: Antioxidants effectively reduce ischemia-reperfusion (IR) injury. The cardioprotective effects of luteolin, a flavonoid that exhibits antioxidant properties and is widely available in many fruits and vegetables, were examined in rats subjected to myocardial IR injury. METHODS AND RESULTS: Rats were subjected to myocardial ischemia or reperfusion injury to evaluate the antiarrhythmic effects of luteolin. Myocardial infarct size was determined histochemically with triphenyltetrazolium chloride staining of the left ventricle. Luteolin was administered intravenously 15min before occlusion of the coronary artery. The incidence and duration of ventricular tachycardia and ventricular fibrillation and mortality during myocardial ischemia were significantly reduced by luteolin (10µg/kg). Similarly, luteolin (1µg/kg) reduced ventricular arrhythmias and mortality during the reperfusion phase. Pretreatment with luteolin decreased plasma lactate dehydrogenase and nitric oxide (NO) levels. Luteolin (10µg/kg) significantly reduced the myocardial infarct size, as well as malondialdehyde production in tissue samples of myocardial IR injury. Luteolin also downregulated inducible NO synthase protein and mRNA expression, but did not significantly alter neuronal NO synthase or endothelial NO synthase expression. CONCLUSIONS: Luteolin is capable of protecting the myocardium against IR injury. The actions of luteolin are at least partly mediated through downregulation of NO production and its own antioxidant properties.

Emergent bedside real-time three-dimensional transesophageal echocardiography in a patient with cardiac arrest following a caesarean section.

Post-caesarean pulmonary embolism (PE) is associated with significant peri-operative morbidity and mortality. This report describes a case of sudden cardiac arrest 2 days post-caesarean due to massive PE diagnosed via bedside transesophageal echocardiography (TEE). Recognition of the PE at the bifurcation of the right and left pulmonary arteries was achieved by real-time three-dimensional TEE, but not two-dimensional TEE. Extracorporeal membrane oxygenation was immediately established and emergent pulmonary thromboembolectomy was performed. The patient was discharged without residual deficits on Day 22 of hospitalization.

Incremental value of live/real time three-dimensional over two-dimensional transesophageal echocardiography in the evaluation of right coronary artery fistula.

We report an adult with a right coronary artery to right atrial fistula in whom live/real time three-dimensional transesophageal echocardiography with its ability to trace the entire course and obtain en face views of the fistula connections, was able to provide significant incremental information over two-dimensional transesophageal echocardiography.

Live three-dimensional transesophageal echocardiography in an unusual case of aorto-left ventricular tunnel with a large interventricular septal aneurysm.

Aorto-left ventricular tunnel (ALVT) is a rare congenital malformation. We report an unusual case of ALVT with a large interventricular septal aneurysm causing severe aortic regurgitation and left ventricular outflow obstruction diagnosed with real time three-dimensional transesophageal echocardiography (3D TEE). Real time 3D TEE allows for assessment and novel views of complex cardiac abnormalities and can aid in perioperative monitoring.

The ability of live three-dimensional transesophageal echocardiography to evaluate the attachment site of intracardiac tumors.

In this study, a case of a right ventricular myxoma and a case of a right ventricular hemangioma are used to demonstrate the ability of live three-dimensional transesophageal echocardiography (3DTEE) to assess the site of tumor attachment. Because 3DTEE has the ability to visualize desired structures in multiple planes, we defined the attached portion of the tumors and measured the en face view dimensions. In addition, the improved ability of 3DTEE to evaluate tissue characteristics allowed differentiation of the heterogeneous myxoma and highly vascular hemangioma. On the contrary, because two-dimensional (2D) TEE only allows structures to be viewed in a 2D plane, the attachment site can be located but complete delineation and measurement of area is not possible. As surgical options become less invasive, accurate attachment site location and size will become more important to ensure complete excision.

Successful transcatheter closure of a residual patent ductus arteriosus with complex anatomy after surgical ligation using an amplatzer ductal occluder guided by live three-dimensional transesophageal echocardiography.

Residual patent ductus arteriosus (PDA) after surgical ligation is not common, but the anatomy of the residual duct may be distorted by the surgical ligation resulting in a difficult transcatheter closure. Such distorted anatomy of the duct may not be demonstrated by the two-dimensional transesophageal echocardiography (2D TEE). Fortunately, live 3D TEE provided the precise anatomy of the elongated distorted residual duct, and as in the case presented herein, guided the Amplatzer ductal occluder (ADO). We concluded that live 3D TEE provided novel images of complex residual ducts and successful guidance of a ductal occluder.