Kuo-Ho Yeh

Radiofrequency and Cryoablation of Atrial Fibrillation in Patients Undergoing Valvular Operations

BACKGROUND Previous studies have shown that the maze operation can restore sinus rhythm and atrial transport function in patients with chronic atrial fibrillation. The purpose of this study was to test the feasibility of the application of radiofrequency and cryoablation as an alternative to the classic maze operation. METHODS Twelve patients undergoing mitral valve procedures were included in this study. Radiofrequency and cryoablation were applied to create lesions in both atria to simulate the classic maze operation. RESULTS There were two surgical deaths. At the mean follow-up of 10.25 months for the remaining 10 patients; 6 were in sinus rhythm, 2 in atrial rhythm, 1 in paroxysmal atrial tachycardia, and 1 in atrial fibrillation. Doppler echocardiography at 6-month follow-up showed emergence of biatrial transport function in 3 patients and right atrial contractility in 8. At 12-month follow-up of 5 patients, Doppler echocardiography showed biatrial transport function in 3 and right atrial contractility in 4. CONCLUSIONS Our modified maze procedure during valvular operation is effective for achieving an acceptable success rate to restore sinus rhythm and atrial transport function in patients with chronic atrial fibrillation.

Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemia–reperfusion injury

This study investigated whether melatonin‐treated adipose‐derived mesenchymal stem cells (ADMSC) offered superior protection against acute lung ischemia–reperfusion (IR) injury. Adult male Sprague‐Dawley rats (n = 30) were randomized equally into five groups: sham controls, lung IR–saline, lung IR–melatonin, lung IR–melatonin–normal ADMSC, and lung IR–melatonin–apoptotic ADMSC. Arterial oxygen saturation was lowest in lung IR–saline; lower in lung IR–melatonin than sham controls, lung IR–melatonin–normal ADMSC, and lung IR–melatonin–apoptotic ADMSC; lower in lung IR–melatonin–normal ADMSC than sham controls and lung IR–melatonin–apoptotic ADMSC; lower in lung IR–melatonin–apoptotic ADMSC than sham controls (P < 0.0001 in each case). Right ventricular systolic blood pressure (RVSBP) showed a reversed pattern among all groups (all P < 0.0001). Changes in histological scoring of lung parenchymal damage and CD68+ cells showed a similar pattern compared with RVSBP in all groups (all P < 0.001). Changes in inflammatory protein expressions such as VCAM‐1, ICAM‐1, oxidative stress, TNF‐α, NF‐κB, PDGF, and angiotensin II receptor, and changes in apoptotic protein expressions of cleaved caspase 3 and PARP, and mitochondrial Bax, displayed identical patterns compared with RVSBP in all groups (all P < 0.001). Numbers of antioxidant (GR+, GPx+, NQO‐1+) and endothelial cell biomarkers (CD31+ and vWF+) were lower in sham controls, lung IR–saline, and lung IR–melatonin than lung IR–melatonin–normal ADMSC and lung IR–melatonin–apoptotic ADMSC, and lower in lung IR–melatonin–normal ADMSC than lung IR–melatonin–apoptotic ADMSC (P < 0.001 in each case). In conclusion, when the animals were treated with melatonin, the apoptotic ADMSC were superior to normal ADMSC for protection of lung from acute IR injury.

Usefulness of Intracardiac Echocardiography in Complex Transseptal Catheterization During Percutaneous Transvenous Mitral Commissurotomy

OBJECTIVE To examine the utility of intracardiac echocardiography in guiding complex transseptal catheterization of patients undergoing percutaneous transvenous mitral commissurotomy. DESIGN We assessed this procedure in high-risk patients in whom transseptal catheterization is technically complex and more demanding. MATERIAL AND METHODS Fifteen patients with mitral stenosis were studied. Twelve patients had giant left atria (70 mm or more), two had atrial septal aneurysms, and one had severe kyphoscoliosis. A newly developed 8-F 10-MHz intracardiac transducer catheter was placed in the right atrium through an 8-F Mullins sheath inserted from the left femoral vein. Echocardiographic images were used to confirm the septal position of the Brockenbrough needle tip before septal punctures. RESULTS Transseptal puncture was successful and uncomplicated in all 15 patients. Use of intracardiac echocardiography eliminated the need for atrial angiography. Before transseptal puncture, the needle tip was identified to be in contact with the atrial septum, as an echogenic point with its acoustic shadow and septal indentation. In addition, in the two patients with aneurysms, puncture of the thin-walled aneurysms was avoided. CONCLUSION Intracardiac echocardiography facilitates safe complex transseptal catheterization in patients with mitral stenosis and giant left atria, atrial septal aneurysms, or severe kyphoscoliosis.

Clinical features and outcome of coronary artery aneurysm in patients with acute myocardial infarction undergoing a primary percutaneous coronary intervention.

Background: While coronary artery aneurysm is an uncommon anatomic disorder and has various forms, its clinical features and outcome and its impact on thrombus formation and the no-reflow phenomenon in the clinical setting of acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (p-PCI) have not been discussed. The purpose of this study was to evaluate whether this anatomic disorder predisposes to a high burden of thrombus formation, and subsequently leads to the no-reflow phenomenon and untoward clinical outcome in patients with AMI undergoing p-PCI. Methods and Results: In our hospital, emergency p-PCI was performed in 924 consecutive patients with AMI between May 1993 and July 2001. Of these 924 patients, 24 patients (2.6%) who had an infarct-related artery (IRA) with aneurysmal dilatation were retrospectively registered and constituted the patient population of this study. Angiographic findings demonstrated that the ectasia type (defined as diffuse dilatation of 50% or more of the length of the IRA) was found most frequently (70%), followed by the fusiform type (20%; defined as a spindle-shaped dilatation in the IRA) and the saccular type (10%; defined as a localized spherical-shaped dilatation in the IRA). The right coronary artery was the most frequently involved vessel (54.2%), followed by the left anterior descending (25.0%) and the left circumflex arteries (20.8%). Coronary angiography revealed that all of these aneurysmal IRA filled with heavy thrombus (indicated as high-burden thrombus formation). The no-reflow phenomenon (defined as ≤TIMI-2 flow) and distal embolization after p-PCI were found in 62.5 and 70.8% of the IRA, respectively. The incidence of cardiogenic shock and the 30-day mortality rate were 25 and 8.3%, respectively. The survival rate was 90.9% (20/22) during a mean follow-up of 19 ± 30 months. Conclusions: While aneurysmal dilatation of an IRA is an uncommon angiographic finding in the clinical setting of AMI, it is frequently associated with high-burden thrombus formation and has a significantly lower incidence of successful reperfusion. However, the long-term survival of these patients is excellent.

Benefit of combined extracorporeal shock wave and bone marrow-derived endothelial progenitor cells in protection against critical limb ischemia in rats*

Objectives:We hypothesized that combined treatment with extracorporeal shock wave and bone marrow-derived endothelial progenitor cells might exert enhanced protection against critical limb ischemia in rats. Methods:Male Sprague-Dawley rats (n = 9 for laser Doppler study and n = 6 for laboratory examinations in each group) were divided into group 1 (sham control), group 2 (critical limb ischemia treated with culture medium), group 3 (critical limb ischemia treated with intramuscular bone marrow-derived endothelial progenitor cells [2.0 × 106 cells]), group 4 (critical limb ischemia treated with extracorporeal shock wave [280 impulses at 0.1 mJ/mm2]), and group 5 (combined bone marrow-derived endothelial progenitor cell-extracorporeal shock wave) after critical limb ischemia induction. Results:By day 21, laser Doppler showed substantially lower ratios of ischemic/normal blood flow in group 2 compared with other groups (p < .001). The protein expressions of mitochondrial cytochrome c, stromal cell-derived factor-1, C-X-C chemokine receptor type 4, vascular endothelial growth factor, and endothelial nitric oxide synthase were remarkably higher in group 5 than in groups 2 to 4, and notably higher in groups 3 and 4 than in group 2 (all p < .01). The messenger RNA expressions of proinflammatory and apoptotic biomarkers and oxidative stress were reduced in group 5 compared with groups 2 to 4, and notably lower in groups 3 and 4 than in group 2 (all p < .01). The messenger RNA expressions of anti-inflammatory and antiapoptotic biomarkers were lower in group 2 than in other groups (all p < .01). Immunofluorescent staining showed higher numbers of CD31+ stromal cell-derived factor-1+, chemokine receptor type 4+, and von Willebrand factor+ cells, and vessels in the ischemic area in group 5 than in groups 2 to 4, and in groups 3 and 4 than in group 2 (all p < .04). Conclusion:Combined treatment with bone marrow-derived endothelial progenitor cells and extracorporeal shock wave is superior to either bone marrow-derived endothelial progenitor cells or extracorporeal shock wave alone in improving ischemia in rodent critical limb ischemia.

Outcomes of patients with Killip class III acute myocardial infarction after primary percutaneous coronary intervention.

Objectives:Little is known about the outcomes of patients with Killip class III acute ST-segment elevation myocardial infarction in the reperfusion era. This study investigated the short- and long-term outcomes of these patients who underwent primary percutaneous coronary intervention. Methods:Between January 2002 and November 2009, a total of 1,278 consecutive patients with acute ST-segment elevation myocardial infarction underwent primary percutaneous coronary intervention. Of these patients, 230 (17.0%) with Killip III, 216 (16.9%) with Killip II, and 832 (65.1%) with Killip I upon presentation were prospectively recruited. Results:Angiographic study showed significantly lower final thrombolysis in myocardial infarction 3 flow in patients with Killip III compared with those with Killip II and I (83.5% vs. 94.9% vs. 95.7%, p < .0001). The incidence of multiple vessel disease was also notably higher in Killip III than in Killip II and I (65.7% vs. 13.9% vs. 53.8%, p < .001). Besides, the incidence of advanced congestive heart failure (defined as greater than or equal to New York Heart Association functional class 3) during hospitalization was remarkably higher in Killip III compared to Killip II and I (71.3% vs. 13.9% vs. 6.6%, p < .001). Furthermore, the 30-day mortality and 1-yr cumulative mortality were notably higher in Killip III than in Killip II and I (20.0% vs. 4.2% vs. 1.7%, p < .001 and 31.7% vs. 7.9% vs. 4%, p < .001, respectively). Multivariate analysis showed that Killip III was independently predictive of 30-day and 1-yr mortality (all p < .04). Conclusion:Killip III remains strongly and independently predictive of 30-day and 1-yr mortality in ST-segment elevation myocardial infarction patients even undergoing primary percutaneous coronary intervention.

Impact of obesity control on circulating level of endothelial progenitor cells and angiogenesis in response to ischemic stimulation

Background and aimWe tested the hypothesis that obesity reduced circulating number of endothelial progenitor cells (EPCs), angiogenic ability, and blood flow in ischemic tissue that could be reversed after obesity control.Methods8-week-old C57BL/6J mice (n = 27) were equally divided into group 1 (fed with 22-week control diet), group 2 (22-week high fat diet), and group 3 (14-week high fat diet, followed by 8-week control diet). Critical limb ischemia (CLI) was induced at week 20 in groups 2 and 3. The animals were sacrificed at the end of 22 weeks.ResultsHeart weight, body weight, abdominal fat weight, serum total cholesterol level, and fasting blood sugar were highest in group 2 (all p < 0.001). The numbers of circulating EPCs (C-kit/CD31+, Sca-1/KDR + and CXCR4/CD34+) were lower in groups 1 and 2 than in group 3 at 18 h after CLI induction (p < 0.03). The numbers of differentiated EPCs (C-kit/CD31+, CXCR4/CD34+ and CD133+) from adipose tissue after 14-day cultivation were also lowest in group 2 (p < 0.001). Protein expressions of VCAM-1, oxidative index, Smad3, and TGF-β were higher, whereas the Smad1/5 and BMP-2, mitochondrial cytochrome-C SDF-1α and CXCR4 were lower in group 2 than in groups 1 and 3 (all p < 0.02). Immunofluorescent staining of CD31+ and vWF + cells, the number of small vessel (<15 μm), and blood flow through Laser Doppler scanning of ischemic area were lower in group 2 compared to groups 1 and 3 on day 14 after CLI induction (all p < 0.001).ConclusionObesity suppressed abilities of angiogenesis and recovery from CLI that were reversed by obesity control.

Comparison of acute versus convalescent stage high-sensitivity C-Reactive protein level in predicting clinical outcome after acute ischemic stroke and impact of erythropoietin

Background and AimCurrently, no data on the optimal time point after acute ischemic stroke (IS) at which high-sensitivity C-reactive protein (hs-CRP) level is most predictive of unfavorable outcome. We tested the hypothesis that hs-CRP levels during both acute (48 h after IS) and convalescent (21 days after IS) phases are equally important in predicting 90-day clinical outcome after acute IS. We further evaluated the impact of erythropoietin (EPO), an anti-inflammatory agent, on level of hs-CRP after acute IS.MethodsTotally 160 patients were prospectively randomized to receive either EPO therapy (group 1, n = 80) (5,000 IU each time, subcutaneously) at 48 h and 72 h after acute IS, or placebo (group 2, n = 80). Serum level of hs-CRP was determined using ELISA at 48 h and on day 21 after IS and once in 60 healthy volunteers.ResultsSerum level of hs-CRP was substantially higher in all patients with IS than in healthy controls at 48 h and day 21 after IS (all p < 0.001). Levels of hs-CRP did not differ between group 1 and 2 at 48 h and day 21 after IS (all p > 0.5). Multivariate analysis showed that hs-CRP levels (at 48 h and day 21) were independently predictive of 90-day major adverse neurological event (MANE) (defined as recurrent stroke, NIHSS≥8, or death) (all p < 0.03), whereas EPO therapy was independently predictive of reduced 90-day MANE (all p < 0.02).ConclusionEPO therapy which was independently predictive of freedom from 90-day MANE did not alter the crucial role of hs-CRP levels measured at 48 h and 21-day in predicting unfavorable clinical outcome after IS.

Apoptotic adipose-derived mesenchymal stem cell therapy protects against lung and kidney injury in sepsis syndrome caused by cecal ligation puncture in rats

IntroductionWe tested the hypothesis that apoptotic adipose-derived mesenchymal stem cells (A-ADMSC) are superior to healthy (H)-ADMSC in attenuating cecal ligation puncture (CLP)-induced sepsis-mediated lung and kidney injuries.MethodsAdult male rats divided into group 1 (sham controls), group 2 (CLP), group 3 [CLP + H-ADMSC administered at 0.5, 6, and 18 hours after CLP], and group 4 [CLP + A-ADMSC administered as in group 3] were sacrificed 72 hours after CLP with blood, lung, and kidney collected for studies.ResultsWhite blood cell (WBC) count, circulating TNF-α and creatinine levels were higher in groups 2 and 3 than in groups 1 and 4 (all P < 0.001). Kidney and lung damage scores were highest in group 2, lowest in group 1, significantly higher in group 3 than in group 4 (all P < 0.0001). Protein expressions of inflammatory (ICAM-1, MMP-9, TNF-α, NF-κB), oxidative, and apoptotic (Bax, caspase-3, PARP) biomarkers were higher in groups 2 and 3 than groups 1 and 4, whereas anti-apoptotic (Bcl-2) and mitochondrial integrity (cytochrome-C) biomarkers were lower in groups 2 and 3 than in groups 1 and 4 (all P < 0.001). Expressions of anti-oxidant biomarkers at protein (GR, GPx, NQO-1, HO-1) and cellular (GR, GPx) levels were highest in group 4 (all P < 0.001). The number of inflammatory cells (CD3+) in lungs and levels of DNA damage marker (γ-H2AX) in kidneys were higher in groups 2 and 3 than in groups 1 and 4 (all P < 0.001).ConclusionsA-ADMSC therapy was superior to H-ADMSC therapy in protecting major organs from damage in rats with CLP-induced sepsis syndrome.

Retention of endothelial progenitor cells in bone marrow in a murine model of endogenous tissue plasminogen activator (tPA) deficiency in response to critical limb ischemia

BACKGROUND This study tested the hypothesis that tissue plasminogen activator (tPA) is crucial for regulating endothelial progenitor cell (EPC) mobilization from bone marrow to circulation in murine critical limb ischemia (CLI) by ligating the left femoral artery. METHODS Wild-type (C57BL/6) (n=40) mice were equally divided into group 1A (sham control), group 2A (CLI), group 3A [control-tPA (4.0 mg/kg)] and group 4A [CLI-tPA (intravenously at 3 h after CLI)]. Similarly, tPA knock-out (tPA(-/-)) mice (n=40) were equally divided into group 1B (sham control), group 2B (CLI), group 3B [control-tPA (4.0 mg/kg)], and group 4B (CLI-tPA). RESULTS The circulating levels of EPCs (C-kit/CD31+, Sca-1/KDR+, CXCR4/CD34+) were lower in groups 1B and 2B than in groups 1A and 2A, respectively (all p<0.01), and were reversed after tPA treatment (3B vs. 3A or 4B vs. 4A, p>0.05) at 6 h and 18 h post-CLI. Levels of these biomarkers decreased again 14 days after CLI in tPA(-/-) mice compared to those in wild-type between the respective groups (all p<0.01). Laser Doppler flowmetry showed a higher ratio of ischemic-to-normal blood flow in 2A than in 2B and in 4A than in 4B by day 14 after CLI (all p<0.05). Angiogenesis at protein (CXCR4, SDF-1α, VEGF) and cellular (CXCR4+, SDF-1α+, and CD31+ cells) levels was highest in animals with CLI-tPA, significantly higher in mice with CLI only than in sham controls for both wild-type and tPA(-/-) mice (p<0.01). CONCLUSION tPA played an essential role in augmenting circulating EPCs, angiogenesis, and blood flow in the ischemic limb in a murine model.