Biomedical subjects
Publications and source records attributed to Hung-Fat Tse.
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OBJECTIVE: To investigate the relationship between obstructive sleep apnea (OSA) and the metabolic syndrome, an established cardiovascular risk factor, in middle-aged Chinese subjects. DESIGN: A prospective cross-sectional study from community-dwelling volunteers. SUBJECTS: Subjects of either sex between 30 and 60 years old were recruited from the staff in public institutions or visitors to community centers in Hong Kong. METHODS: Demographic and anthropomentric indices, blood pressure and metabolic profile (fasting blood glucose, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglycerides) were measured. Overnight polysomnographic studies were conducted. Presence of obstructive sleep apnea (OSA) was defined as apnea-hypopnea index (AHI)5. Metabolic syndrome was defined by the criteria of the National Cholesterol Education Panel, but using Asian cut-off values for abdominal obesity. RESULTS: A total of 255 subjects (150 men, 105 women) were studied. Subjects with OSA had five-fold risk of having metabolic syndrome. OSA was associated with the metabolic syndrome or its components, including waist circumference, diastolic blood pressure and fasting glucose, after adjusting for confounding variables. The independent determinants of OSA were age, gender, body mass index (BMI) and the metabolic syndrome. CONCLUSION: Among community-based middle-aged Chinese subjects, the metabolic syndrome was independent predictor of OSA.
Patients on warfarin for mechanical heart valves are at increased risk for thromboembolic events and intracranial hemmorhage. In current guidelines, a low dose of vitamin K is the recommended treatment for moderate over-anticoagulation based on studies in which only minority patients participating had mechanical heart valves. We performed a randomized controlled trial to compare the efficacy and safety profile of low-dose intravenous vitamin K and fresh frozen plasma (FFP) for patients with mechanical heart valves and mild to moderate over-anticoagulation (international normalized ratio [INR] 4 to 7). In a 24-month period, we randomized 102 patients to (1) vitamin K or (2) FFP. The baseline INR at presentation between the vitamin K group and the FFP group was 4.61 +/- 0.007 vs 4.78 +/- 0.07 (p = 0.11). Six hours after treatment, patients in the FFP group had a significantly lower mean INR compared with the vitamin K group (2.75 +/- 0.06 vs 3.44 +/- 0.10, p = 0.01). No patient in both groups had over-correction (INR < 2). One week later, there was no significant difference in mean INR between both groups (2.7 +/- 0.11 vs 2.56 +/- 0.12, p = 0.41). Fifty-eight percent of patients in the FFP group and 51% in the vitamin K group had an INR within the target range. There were no adverse reactions or outcomes in both groups. In conclusion, intravenous low-dose vitamin K is a safe alternative to FFP infusion for warfarin overdose in patients with mechanical heart valves.
Previous studies have shown that more complete platelet inhibition improves the coronary flow reserve (CFR), a measure of microvascular integrity, in patients undergoing percutaneous coronary intervention (PCI). We hypothesized that patients with aspirin resistance would have impaired CFR after elective PCI. We used VerifyNow Aspirin to determine the response to aspirin in 117 consecutive patients who underwent elective single-lesion PCI. The assay results are expressed quantitatively in Aspirin Reaction Units based on the degree of platelet aggregation. All patients received a 300-mg loading dose of clopidogrel >12 hours before and a 75-mg maintenance dose the morning of PCI. CFR was estimated using the Thrombolysis In Myocardial Infarction frame count method. Of the 117 patients, 22 (18.8%) were aspirin resistant. The clinical, angiographic, and procedural characteristics of the aspirin-sensitive and -resistant patients were balanced. All patients underwent successful PCI with <50% residual diameter stenosis and Thrombolysis In Myocardial Infarction grade 3 flow after PCI. Aspirin-resistant patients had a lower CFR than the aspirin-sensitive patients (1.42 +/- 0.35 vs 1.80 +/- 0.64, p = 0.018). Univariate correlates of CFR included the Aspirin Reaction Unit (r = -0.227, p = 0.014) and post-PCI creatine kinase-MB elevation (p = 0.048). Multivariate linear regression analysis revealed the Aspirin Reaction Unit to be the only independent determinant of CFR after PCI (r2 = 0.051, p = 0.014). Thus, aspirin resistance was associated with impaired CFR in patients who underwent elective PCI, implicating insufficient aspirin-induced platelet inhibition as a cause of microvascular dysfunction by distal atherothrombotic embolization and/or spasm.
Pluripotent embryonic stem cells (ESCs) possess promising potential for cell-based therapies, but their electrophysiological properties have not been characterized. Here we describe the presence of ionic currents in mouse (m) and human (h) ESCs and their physiological function. In mESCs, tetraethylammonium (TEA)-sensitive depolarization-activated delayed rectifier K+ currents (IK(DR)) (8.6 +/- 0.9 pA/pF at +40 mV; IC50 = 1.2 +/- 0.3 mM), which contained components sensitive to 4-aminopyridine (4-AP) (IC50 = 0.5 +/- 0.1 mM) and 100 nM Ca2+-activated K+ current (IK(Ca)) blocker iberiotoxin (IBTX),were detected in 52.3% of undifferentiated cells.IK(DR) was similarly present in hESCs (approximately 100%) but with an approximately sixfold higher current density (47.5 +/- 7.9 pA/pF at +40 mV). When assayed by bromodeoxyurindine incorporation, application of TEA, 4-AP, or IBTX significantly reduced the proliferation of mESCs and hESCs in a dose-dependent manner (p < .05). A hyperpolarization-activated inward current (I(h)) (-2.2 +/- 0.4 pA/pF at -120 mV) was detected in 23% of mESCs but not hESCs. Neither Na(v) nor Ca(v) currents were detected in mESCs and hESCs. Microarray and reverse transcription-polymerase chain reaction analyses identified several candidate genes for the ionic currents discovered. Collectively, our results indicate that pluripotent ESCs functionally express several specialized ion channels and further highlight similarities and differences between the two species. Practical considerations for the therapeutic use of ESCs are discussed.
It has been demonstrated that higher degree of arteriolar retinopathy is associated with greater cardiovascular risk, and hyperhomocysteinaemia is also related to increased cardiovascular risk, but interacts with other risk factors, particularly smoking. It still remains unclear regarding relationships of smoking, fasting plasma total homocysteine (tHcy) levels and arteriolar retinopathy. This study was aimed to investigate the relationship and influence of smoking and tHcy levels on degree of arteriolar retinopathy. Two hundred and forty-three subjects were enrolled from an annual health examination. The arteriolar retinopathy was examined by direct ophthalmoscopy. Dundett ANOVA showed that geometric mean of tHcy levels were 11.5+/-1.54 versus 11.2+/-1.41 versus 17.6+/-1.92 (P1=0.883, P2=0.001) in subjects with no arteriolar retinopathy (as control group), grades I and II retinopathy, respectively. Furthermore, multiple linear regression analysis showed that only smoking consumption (P<0.001), gender (P=0.012) and presence of hypertension (P=0.041) were independent determinants of plasma tHcy levels. After females were excluded, T-test showed a significant differences in tHcy levels (15.6+/-1.56 micromol/L versus 12.4+/-1.45 micromol/L, P=0.003) and in prevalence of grade II retinopathy (25.4% versus 9.3%, P=0.029), but no difference in other variables or prevalence of overall retinopathy between smokers and non-smokers. Finally, logistic regression showed that smoking (OR 4.19, 95% CI 1.17-15.0) was a stronger predictor than hyperhomocysteinaemia (OR 2.14, 95% CI 0.85-5.41) for presence of grade II retinopathy. This study showed that smoking was related to increased plasma tHcy levels in subjects with grade II retinopathy, and it could independently contribute to facilitating the progression of arteriolar retinopathy.
Inappropriate shock from implantable cardioverter defibrillator (ICD) may result from external electromagnetic interference (EMI), especially for unipolar ventricle sensing. Previous case reports and small in-vitro safety study suggested that endocardial bipolar lead system may be immune from EMI resulting from transcutaneous electrical neuromuscle stimulation (TENS) therapy. This report presents an unusual case of inappropriate discharge in a patient with ICD of endocardial bipolar lead system, receiving TENS from a commercially available device.
PURPOSE: We sought to investigate the association of aspirin dose and aspirin resistance in stable coronary artery disease patients measured by a point-of-care assay. METHODS: We studied 468 consecutive stable coronary artery disease patients in a referral cardiac center who were taking aspirin 80 to 325 mg daily for > or =4 weeks. The VerifyNow Aspirin (Ultegra RPFA-ASA, Accumetrics Inc, San Diego, Calif) was used to determine aspirin responsiveness. An aspirin reaction unit (ARU) > or =550 indicates the absence of aspirin-induced platelet dysfunction, based on correlation with epinephrine-induced light transmission aggregometry. Demographic and clinical data were collected to analyze the predictors of aspirin resistance. RESULTS: Aspirin resistance was noted in 128 (27.4%) patients. Univariate predictors of aspirin resistance include elderly (P = 0.002), women (P <0.001), anemia (P <0.001), renal insufficiency (P = 0.009) and aspirin dose < or =100 mg (P = 0.004). Multivariate analysis revealed hemoglobin (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.51 to 0.69; P <0.001) and aspirin dose < or =100 mg (OR 2.23; 95% CI 1.12 to 4.44; P = 0.022) to be independent predictors of aspirin resistance. Daily aspirin dose < or = 100 mg was associated with increased prevalence of aspirin resistance compared with 150 mg and 300 mg daily (30.2% vs 16.7% vs 0%, P = 0.0062). CONCLUSION: A 100 mg or less daily dose of aspirin, which may have lower side effects, is associated with a higher incidence of aspirin resistance in patients with coronary artery disease. Prospective randomized studies are warranted to elucidate the optimal aspirin dosage for preventing ischemic complications of atherothrombotic disease.
UNLABELLED: Lesion dimension of cryoablation. BACKGROUND: Transvenous catheter cryoablation is a novel technique for treating cardiac arrhythmias. However, the relative importance of temporal application parameters on lesion dimension and clinical efficacy has not been studied. METHODS AND RESULTS: We investigated the effects of (1) application duration: single 2.5 (2.5x1) versus single 5 versus double 2.5 (2.5x2) versus double 5 (5x2) minutes, (2) number of freeze-thaw cycles: single versus double, and (3) electrode contact area: horizontal versus vertical orientation, on the lesion diameter and depth during catheter cryoablation (10F, 6.5-mm tip-electrode, CryoCor, San Diego) in a thigh muscle preparation. A total of 175 lesions (horizontal=90, vertical=85) were created in thigh muscle preparations on 10 swine. The lesion diameter and depth were significantly greater using 2.5x2 and 5x2 application modes as compared with 2.5x1 applications (P<0.05). Horizontal tip-electrode orientation produced larger lesion diameter (P<0.05), but not lesion depth as compared with vertical orientation. Multivariate analysis demonstrated that both tip-electrode orientation and duration of freeze >2.5 minutes were independent predictors for lesion diameter (P<0.001). However, only duration of freeze >2.5 minutes was an independent predictor for lesion depth (P<0.001). CONCLUSIONS: The dimensions of lesions created by catheter cryoablation are affected by mode of cryoablation application and electrode orientation. Increasing the duration of application, employing multiple freeze-thaw cycles at shorter cycle durations, and orienting the catheter to enhance/increase tissue contact can create a larger lesion.
UNLABELLED: Cardiac resynchronization therapy. BACKGROUND: A significant proportion of patients with dilated cardiomyopathy and left bundle branch block (LBBB) do not respond to cardiac resynchronization therapy (CRT). The purpose of this study was to investigate whether the electromechanical properties of the myocardium would predict acute hemodynamic improvement during left ventricular (LV) pacing. METHODS AND RESULTS: We studied 10 patients with idiopathic dilated cardiomyopathy and LBBB (ejection fraction (EF): 27%+/-7%; QRS duration: 166+/-16 msec) using three-dimensional electromechanical endocardial mapping technique to assess endocardial activation time (Endo-AT), unipolar voltage, and local linear shortening during sinus rhythm. LV stimulation was performed in VDD mode at five different sites and three atrioventricular delays within the coronary sinus. LV+dP/dtmax changes from baseline were measured during LV stimulation at each site (%DeltadP/dtmax). There was no significant relationship between maximum %DeltadP/dtmax during LV stimulation at the best coronary sinus site and LV EF, baseline LV+dP/dtmax, total LV Endo-AT, baseline QRS duration nor changes in QRS duration during LV pacing. However, the maximum %DeltadP/dtmax was significantly positively correlated with percentage area of late Endo-AT (r=0.97, P<0.001) and preserved LV myocardium (r=0.81, P=0.005), respectively. Patients with >20% of LV area with late Endo-AT and >30% of preserved LV myocardium had five times better acute hemodynamic response with LV stimulation. Multivariate analysis showed that only percentage area of late Endo-AT was independently correlated with %DeltadP/dtmax (P<0.05). CONCLUSION: The presence of a larger amount of LV area with late Endo-AT and preserved LV myocardium measured by electromechanical mapping could identify patients who have better acute improvement in systolic performance during LV stimulation.
There are only limited data on the prevalence and risk factors for postoperative atrial fibrillation (AF) after elective abdominal surgery. We retrospectively studied the clinical characteristics and hospital outcomes in 563 consecutive patients (mean age: 67 +/- 13 years, 245 men) with colorectal cancer who underwent elective colectomy. The baseline clinical characteristics of patients who underwent open (OC) versus laparoscopic colectomy (LC) were similar. Postoperative AF developed in 25 patients (4.4%). Patients who developed postoperative AF were older (P = 0.017), had a higher prevalence of hypertension (P = 0.05), more major postoperative events (P = 0.02), an elevated neutrophil count on postoperative day (POD) 1 (P = 0.007), longer hospitalizations (P = 0.02), and were more likely to undergo OC (P = 0.067). In multiple regression analysis, independent predictors of postoperative AF were OC (odd ratio: 3.3, 95% confidence interval: 1.3-8.0, P = 0.008), and an elevated neutrophil count on POD 1 (odd ratio: 3.2, 95% confidence interval: 1.3-7.8, P = 0.01). The incidence of postoperative AF after elective colorectal cancer surgery was approximately 4%. Postoperative AF was more commonly observed in patients with OC versus LC and in those with elevated postoperative neutrophil counts.
Upon standing from a supine position, the normal response is an increase in heart rate to maintain blood pressure (BP). In patients with chronotropic incompetence, heart rate may not increase upon standing, and they may experience orthostatic hypotension (OH). We evaluated a new orthostatic response (OSR) pacing algorithm that uses an accelerometer signal to detect sudden activity following prolonged rest to trigger a 2 minutes increase in pacing rate to 94 bpm. Ten recipients of DDDR pacemakers which contain the OSR compensation algorithm (mean age = 77 +/- 9 years, 8 women) with sick sinus syndrome (n = 6) or atrioventricular block (n = 4) were studied. In all patients BP was measured before and 0.5, 1, 1.5, 2, and 3 minutes after standing at their programmed base rate. A 20 mmHg fall in systolic BP upon standing was observed in five patients (OH patients), while the other five were considered non-OH patients. The measurements were repeated with the OSR algorithm turned on. Mean BP was defined as 1/3 systolic BP + 2/3 diastolic BP. Baseline heart rate was significantly slower in OH patients (62 +/- 2 bpm) than non-OH patients (71 +/- 7 bpm, P < 0.05). In OH patients mean BP increased significantly upon standing (P < 0.05 for all comparisons) with the algorithm ON instead of decreasing with the algorithm OFF, at 1 minute (+3.4 vs -10.3 mmHg), 1.5 minutes (+7.0 vs -4.9 mmHg), 2 minutes (+1.6 vs -6.7 mmHg), and 3 minutes (+2.5 vs -8.5 mmHg). These preliminary results suggest that the OSR algorithm maintains BP upon standing in patients with OH.
BACKGROUND: Recent studies have demonstrated that transvenous cryoablation is a safe and feasible method for pulmonary vein (PV) isolation for treatment of atrial fibrillation (AF). However, this technique is limited by a much longer ablation time than conventional radiofrequency ablation. The aim of this study was to determine the effect of duration of cryoablation application with double freeze-thaw cycles on clinical efficacy for PV isolation for treatment of AF. MATERIALS AND RESULTS: We compared the clinical efficacy and procedural time of cryoablation (CryoCorTM, San Diego, CA, USA) for segmental PV isolation in 30 patients (mean age 51 +/- 13, 20 men) with paroxysmal AF using either double 5-minute (n = 15) or double 2.5-minute (n = 15) freeze-thaw cycle delivered with a 10 F deflectable transvenous catheter. Clinical recurrence of AF and the occurrence of PV stenosis as determined by computer tomography of the thorax were performed at 3- and 12-month follow-up. Acute successful electrical isolation of PV was achieved with cryoablation in 96 of 98 (98%) targeted PVs in 30 patients (mean: 3.2 +/- 0.8 PVs per patient). There were no significant differences between the baseline characteristics, the number of PV isolated per patient, the total number and percentage of effective cryoablation and the acute clinical efficacy between using double 5-minute and double 2.5-minute freezes (P > 0.05). However, the fluoroscopy time (107 +/- 43 vs 138 +/- 113 minutes, P = 0.06) and the procedural time (360 +/- 113 vs 510 +/- 115 minutes, P = 0.01) of using double 2.5-minute freezes was reduced by approximately 30% compared with double 5-minute freezes. At a mean of 20 +/- 8 month follow-up, there was no significant difference in the chronic clinical efficacy of cryoablation in terms of freedom from AF in the absence of antiarrhythmic drug therapy between using double 5-minute (6/15, 40%) and double 2.5-minute freezes (7/15, 46%, P = 0.98). CONCLUSION: As compared with double 5-minute freeze, the use of a shorter double 2.5-minute freeze protocol significantly reduces the procedural time without affecting the acute and long-term clinical efficacy of cryoablation to isolate PV for treatment of AF.
BACKGROUND: Recent studies have demonstrated that transvenous catheter cryoablation is a safe and effective technique for creating pulmonary veins (PVs) electrical isolation for the treatment of atrial fibrillation (AF). However, the impacts of this procedure on quality-of-life (QoL) have not been evaluated. METHODS AND RESULTS: We studied the effects of PV isolation using transvenous catheter cryoablation on QoL in 46 patients (34 men, mean age: 50 +/- 12 years) with drug-refractory AF. QoL was assessed by Medical Outcomes Study Short Form-36 (SF-36) and Symptom Checklist at baseline and 3-month after cryoablation, and compared with those in a sex-age matched normal control. At 3-month follow-up, 24 of 46 patients (52%) had no recurrence of AF, including 11 patients who were not taking antiarrhythmic drugs. At baseline, patients with AF had significantly lower QoL scores in overall and in 5/8 subscales of SF-36 than the sex-age matched control group (P < 0.05). In patients with successful outcome after cryoablation showed a significant improvement in overall and in 5/8 subscales of SF-36 QoL scores have significantly increased as compared with the baseline (P < 0.05). Furthermore, their QoL scores in overall and in 6/8 subscales of SF-36 were similar to the sex-age matched control group (P > 0.05). The Symptom Checklist also showed significant reduction in both the symptoms frequency scores and symptoms severity scores at 3-month follow-up as compared with baseline (P < 0.05). CONCLUSIONS: Successful PV isolation using transvenous catheter cryoablation is associated with significant reduction in the frequency and severity of AF symptoms and improvement in the general QoL, reaching the levels of normal controls.
BACKGROUND: Radiofrequency (RF) ablation procedures for atrial fibrillation (AF) are associated with potential risks of thromboembolism, which may be minimized by the use of cryoablation that preserves the integrity of endocardium. The objective of this study was to compare the thrombogenic potential of transvenous cryoablation versus RF ablation during pulmonary vein (PV) isolation. METHODS AND RESULTS: Thirty consecutive patients with paroxysmal AF were randomized to undergo segmental PV isolation procedure using 4-mm tip RF ablation (n = 15) or cryoablation (CryoCor, San Diego, CA, USA) (n = 15). Blood samples were drawn after sheath insertion (baseline), after transseptal puncture, before ablation (after heparin administration), and after isolation of a superior PV. Activation of coagulation was measured with plasma levels of prothrombin fragment 1 + 2 (F1 + 2) and thrombin-antithrombin III complex (TAT), and platelets by plasma level of beta-thromboglobulin (beta-TG) and flow cytometric enumerating of P-selectin (CD62)-positive platelets. In both groups, the plasma level of beta-TG, F1 + 2, and TAT were elevated after sheath insertion. The percentage changes in plasma level of beta-TG, F1 + 2, and TAT and CD41/62-positive platelets from baseline after transseptal puncture and before ablation were similar (P > 0.05). However, the percentage changes in CD62-positive platelets from baseline were significantly higher in patients treated with RF ablation (82 +/- 20%) than with cryoablation (22 +/- 14%, P = 0.02), although their plasma levels of beta-TG, F1 + 2, and TAT were not different (P > 0.05). CONCLUSIONS: Significant platelet and coagulation activations were observed during PV ablation procedures, and heparin administration only prevented activation of coagulation but not platelets. Persistent platelets activation was observed during RF energy application, but not during cryoablation.
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OBJECTIVES: Coronary stenting is associated with a high incidence of restenosis in patients with diabetes mellitus. Recent data suggest that diabetic patients treated with abciximab have a lower rate of target vessel revascularization (TVR). We sought to investigate whether abciximab can reduce in-stent restenosis after coronary stenting in diabetic patients. METHODS: In this prospective double-blind trial, we randomly assigned 254 patients with type 2 diabetes mellitus undergoing nonurgent coronary stenting to receive abciximab with an initial heparin bolus of 50 U/kg (n = 128) or placebo with an initial heparin bolus of 70 U/kg (n = 126). All patients received aspirin and clopidogrel before the procedure. The primary endpoint was angiographic restenosis by quantitative coronary angiography at 6 months. The secondary endpoint was death, myocardial infarction (MI), or target lesion revascularization (TLR) at 6 months. RESULTS: The clinical, angiographic, and procedural characteristics were matched between the 2 groups. Angiographic follow-up was completed in 226 patients (90%). Angiographic restenosis occurred in 29.1% of the abciximab group, and 24% of the placebo group (p = 0.30). The rates of the secondary endpoint were similar between the 2 groups (23.4% in the abciximab group versus 22.2% in the placebo group; p = 0.88). TLR was performed on 36 (18.4%) lesions in 29 (23.4%) patients of the abciximab group, and 26 (13.6%) lesions in 23 (18.3%) patients of the placebo groups, respectively (p = 0.21 and 0.35, respectively). CONCLUSIONS: Abciximab does not reduce angiographic restenosis or TLR in type 2 diabetic patients undergoing nonurgent coronary stenting.
The aim of this study was to investigate the effect of the Ventricular Response Pacing (VRP) algorithm, which regularizes ventricular rate during atrial fibrillation (AF), on symptoms, quality of life, and functional capacity. VRP regularizes the ventricular rate during AF without increasing the mean ventricular rate, thereby reducing the severity of AF-related symptoms in patients with persistent AF. However, VRP did not improve general quality of life (Medical Outcomes Study 36-item Short-Form General Health Survey), the performance of routine activities (Duke Activity Status Index), or functional capacity (hall walk) in patients with AF.