Hung-Wen Tsai

Correctness of multi-detector-row computed tomography for diagnosing mechanical prosthetic heart valve disorders using operative findings as a gold standard

The purpose was to compare the findings of multi-detector computed tomography (MDCT) in prosthetic valve disorders using the operative findings as a gold standard. In a 3-year period, we prospectively enrolled 25 patients with 31 prosthetic heart valves. MDCT and transthoracic echocardiography (TTE) were done to evaluate pannus formation, prosthetic valve dysfunction, suture loosening (paravalvular leak) and pseudoaneurysm formation. Patients indicated for surgery received an operation within 1 week. The MDCT findings were compared with the operative findings. One patient with a Björk-Shiley valve could not be evaluated by MDCT due to a severe beam-hardening artifact; thus, the exclusion rate for MDCT was 3.2% (1/31). Prosthetic valve disorders were suspected in 12 patients by either MDCT or TTE. Six patients received an operation that included three redo aortic valve replacements, two redo mitral replacements and one Amplatzer ductal occluder occlusion of a mitral paravalvular leak. The concordance of MDCT for diagnosing and localizing prosthetic valve disorders and the surgical findings was 100%. Except for images impaired by severe beam-hardening artifacts, MDCT provides excellent delineation of prosthetic valve disorders.

A nanoscale drug-entrapment strategy for hydrogel-based systems for the delivery of poorly soluble drugs.

The hydrophilic nature of hydrogel matrices makes them disadvantageous to entrap poorly soluble therapeutic agents and greatly restricts their applications as drug-delivery systems. In this study, we demonstrated that sustained delivery of lipophilic drugs in hydrogel-based devices can be readily achieved by enhancing retention of drugs within micelles. This nanoscale drug-entrapment strategy was applied to develop a polymeric drug-eluting stent. Sirolimus, a lipophilic anti-proliferative/immunosuppressive drug, was entrapped into the hydrophobic core of Pluronic L121 micelles and then blended in a chitosan-based strip and crosslinked by an epoxy compound to fabricate test stents. It was found that the use of such a nanoscale drug-entrapment strategy was able to significantly increase the loading efficiency of lipophilic drugs, prevent the drug from aggregation and beneficially reduce its initial burst release; thus, the duration of drug release was extended considerably. When implanting the stent in rabbit infrarenal abdominal aortas, in-stent restenosis was markedly reduced and less inflammatory reaction was observed, while unfavorable effects such as delayed endothelial healing caused by the overdose of sirolimus could be significantly evaded.

The characteristics and in vivo suppression of neointimal formation with sirolimus-eluting polymeric stents.

Drug-eluting stents have emerged as a predominant percutaneous strategy in patients with coronary artery disease. However, hypersensitivity reactions caused by their nonerodable polymer coatings and bare-metal stents may result in serious clinical sequelae. In this report, a new biodegradable sirolimus-eluting stent, made from chitosan-based strips fixed by an epoxy compound, coated with a hydrophobic heparin was developed. Due to the covalent crosslinks formed in the stent matrix, the fabricated stent had a shape-memory property to memorize its permanent shape. The shape-memory ability and mechanical strength of the stent could be enhanced by increasing its degree of crosslinking. The cytocompatibility of the stent was demonstrated in vitro. The heparin coating on the stent effectively reduced platelet adhesion; additionally, it acted as a diffusion barrier and led to a nearly linear sustained-release profile of sirolimus. Cell-cycle analysis demonstrated that the released sirolimus could inhibit smooth muscle cell proliferation by inducing cell-cycle arrest in G(1) phase. When compared to the unloaded stent, neointimal formation was significantly suppressed after implantation of the sirolimus-eluting stent in rabbit infrarenal abdominal aortas. These findings suggested that the developed sirolimus-eluting polymeric stent can be a potential alternative for treatment of atherosclerosis.

Mechanical properties, drug eluting characteristics and in vivo performance of a genipin-crosslinked chitosan polymeric stent

A limitation with the use of polymers as stent matrices is their inherent mechanical weakness. In this study, a polymeric stent, made from chitosan-based films fixed by genipin which has a cyclic molecular structure, was developed (the genipin stent). The mechanical properties of the genipin stent were investigated; its counterpart fixed by a linear epoxy compound (the epoxy stent) and a commercially available metallic stent were used as controls. The results indicated that the cyclic crosslinking structures formed within the genipin stent matrix were beneficiary to the improvement of its mechanical property. Additionally, the tolerable compression load of the genipin stent was superior to that of the control metallic stent. The cytotoxicity of the genipin stent was significantly lower than the epoxy stent. The deployment of the genipin stent in rabbit infrarenal abdominal aortas was performed using a French sheath. At 3 months postoperatively, the retrieved arteries remained patent; no thrombosis was observed. A nearly intact layer of endothelial cells was seen on the stent-implanted vessel wall. To evaluate its possibility as a drug delivery vehicle, sirolimus (an anti-proliferative drug) was loaded in the genipin stent. It was found that the genipin stent with heparin coating exhibited a linear sustained-release profile and the released sirolimus still possessed its original activity in inhibiting smooth muscle cell proliferation. These findings suggest that the genipin stent with enhanced mechanical strength can be used as an attractive stent platform for local drug delivery.

Core-shell cell bodies composed of human cbMSCs and HUVECs for functional vasculogenesis.

Rapid induction and creation of functional vascular networks is essential for the success of treating ischemic tissues. The formation of mature and functional vascular networks requires the cooperation of endothelial cells (ECs) and perivascular cells. In the study, we used a thermo-responsive hydrogel system to fabricate core-shell cell bodies composed of cord-blood mesenchymal stem cells (cbMSCs) and human umbilical vascular ECs (HUVECs) for functional vasculogenesis. When seeded on Matrigel, the shelled HUVECs attempted to interact and communicate vigorously with the cored cbMSCs initially. Subsequently, HUVECs migrated out and formed tubular structures; cbMSCs were observed to coalesce around the HUVEC-derived tubes. With time progressing, the tubular networks continued to expand without regression, indicating that cbMSCs might function as perivascular cells to stabilize the nascent networks. In the in vivo study, cbMSC/HUVEC bodies were embedded in Matrigel and implanted subcutaneously in nude mice. At day 7, visible blood-filled vessels were clearly identified within the implant containing cbMSC/HUVEC bodies, indicating that the formed vessels anastomosed with the host vasculature. The cored cbMSCs were stained positive for smooth muscle actin, suggesting that they underwent smooth muscle differentiation and formed microvessels with the shelled HUVECs, as the role of perivascular cells. These data confirm that the formation of mature vessels requires heterotypic cooperation of HUVECs and MSCs. This study provides a new strategy for therapeutic vasculogenesis, by showing the feasibility of using cbMSC/HUVEC bodies to create functional vascular networks.

A translational approach in using cell sheet fragments of autologous bone marrow-derived mesenchymal stem cells for cellular cardiomyoplasty in a porcine model

Based on a porcine model with surgically created myocardial infarction (MI) as a pre-clinical scheme, this study investigates the clinical translation of cell sheet fragments of autologous mesenchymal stem cells (MSCs) for cellular cardiomyoplasty. MSC sheet fragments retaining endogenous extracellular matrices are fabricated using a thermo-responsive methylcellulose hydrogel system. Echocardiographic observations indicate that transplantation of MSC sheet fragments in infarcted hearts can markedly attenuate the adverse ventricular dilation and preserve the cardiac function post MI, which is in contrast to the controlled groups receiving saline or dissociated MSCs. Additionally, histological analyses suggest that administering MSC sheet fragments significantly prevents the scar expansion and left ventricle remodeling after MI. Immunohistochemistry results demonstrate that the engrafted MSCs can differentiate into endothelial cells and smooth muscle cells, implying that angiogenesis and the subsequent regional perfusion improvement is a promising mechanism for ameliorating post-infarcted cardiac function. However, according to the data recorded by an implantable loop recorder, the transplanted MSCs may provoke arrhythmia. Nevertheless, the proposed approach may potentially lead to the eventual translation of MSC-based therapy into practical and effective clinical treatments.

Determinants of in-hospital mortality after surgery for acute type a aortic dissection

BACKGROUND AND PURPOSE Acute type A aortic dissection presents a formidable challenge for the cardiac surgeon, although remarkable improvements have been achieved in diagnosis, surgical techniques and perioperative management. The aim of this study was to identify the most important variables associated with in-hospital mortality in patients undergoing surgery for this condition. METHODS Between July 1998 and June 2002, 80 patients underwent surgery for acute type A aortic dissection. Univariate and multivariate analyses were performed to identify the variables independently correlated with in-hospital mortality. RESULTS The overall in-hospital mortality rate was 20% (16/80 patients). Univariate analysis revealed 24 preoperative and operative variables, including type of surgery, cardiopulmonary bypass (CPB) time, aortic cross-clamp time, diabetes mellitus, and postoperative (postoperative 24 hours) bleeding > or = 1500 mL, as factors associated with in-hospital death. Stepwise logistic regression analysis showed the factors independently associated with in-hospital death were CPB time, diabetes mellitus, and postoperative bleeding > or = 1500 mL (p <0.05). CONCLUSIONS Multiple factors affect in-hospital mortality after surgery for acute type A aortic dissection. This study suggests that CPB time, diabetes mellitus and postoperative bleeding > or = 1500 mL are the main determinants of in-hospital death.

Mediastinal diffuse large B-cell lymphoma invading the left atrium mimicking coronary artery disease with a mural thrombus

A left atrial mass associated with coronary artery disease is often diagnosed as a mural thrombus rather than other possible etiologies such as benign primary cardiac tumor (myxoma, lipoma), a malignant primary cardiac tumor (sarcoma, lymphoma), or secondary involvement for extracardiac tumors. Malignant lymphoma initially presenting as intracardiac masses is very rare. Chest computed tomography with contrast enhancement and cardiac magnetic resonance may be the best methods for distinguishing primary cardiac tumors from direct extension from adjacent mediastinal structures. We report the case of a 59-year-old man with incidentally found mediastinal diffuse large B-cell lymphoma invading the left atrium, which presented with coronary artery disease and a left atrial mass. Improvement in cardiac ventricular function heart after coronary artery bypass grafting may provide the patient with a better chance of receiving an adequate dose of chemotherapy.

Perforation of Cardiac Wall by Cement Embolism after Vertebral Augmentation for Thoracic Spinal Fracture: A Case Report

We describe a rare case of cardiac perforation caused by cement emboli after vertebral augmentation technique two months after the procedure. The patient was sent to a local hospital due to progressive dyspnea and chest tightness. Massive pericardial effusion was first diagnosed at the hospital, and therefore he was transferred to our hospitals emergency department. Multidetector computed tomography (MDCT) showed a string-like foreign body over the right atrium and ventricle which had apparently caused perforation of cardiac wall. Under the diagnosis of cement spike perforation, we performed percutaneous endovascular retrieval. We failed to extract the cement due to its fragile characteristic of the fragment and further migration of cement into the right middle lobe of lung was noted. The patients symptoms improved after the penetrating emboli was removed from the cardiac wall, and no symptoms of pulmonary embolism occurred. The patient was discharged 5 days later with aspirin treatment for prevention of pulmonary embolism.

Prosthetic mitral valve obstructed by occluder device for paravalvular leak.

70-year-old man, with the history of rheumatic Amitral valvulopathy, prosthetic mitral valve replacement, and two subsequent surgical reinterventions for infective endocarditis and paravalvular leak, presented with severe hemolytic anemia. Paravalvular leak of his prosthetic mitral valve was diagnosed. He received closure with two Amplatzer duct occluders and had symptomatic improvement. Unexpectedly, poor motion of the prosthetic valve was noted 5 months later. Multidetector-row computed tomography revealed closure of both leaflets of the mitral prosthesis in systole (Fig 1A; Ao 1⁄4 aorta; LA 1⁄4 left atrium; LV 1⁄4 left ventricle). During diastole (Fig 1B), one of the valve leaflets