[show abstract][hide abstract] ABSTRACT: Background. T-box expressed in T cells (TBET) and guanine adenine thymine adenine sequence-binding protein 3 (GATA3) play important roles in the differentiation of Th1 and Th2 subsets, which contributes to the progression of acute coronary syndrome (ACS). Objective. This study aimed to investigate the temporal change of TBET/GATA3 mRNA ratio in ACS. Methods. Thirty-three patients suspected of ACS with symptom onset within 24 hours were recruited. Blood samples were taken after arrival at the emergency department and at hourly intervals until the 6th hour. The mRNA expressions of TBET and GATA3 were quantified by a real-time RT-qPCR. Results. The TBET/GATA3 mRNA ratio was elevated dramatically in patients with acute myocardial infarction (AMI) and exhibited biphasic M-shaped release kinetics with two distinct peaks. The ratio was elevated 2 hours after symptom onset, dropped to the lowest level at 10 hours, and rose to the second peak at 14 hours. A similar biphasic M-shaped curve was observed in AMI patients with blood samples taken prior to any intervention. Conclusions. The TBET/GATA3 mRNA ratio was elevated in AMI patients throughout most of the first 20 hours after symptom onset. The biphasic M-shaped release kinetics was more likely to reflect pathophysiological changes rather than treatment effects.
[show abstract][hide abstract] ABSTRACT: Left ventricular (LV) diastolic dysfunction has been reported in both active and inactive systemic lupus erythematosus (SLE) patients without clinical evidence of cardiovascular disease. However, the relationship between the long-term inflammatory burden reflected by the SLICC/ACR damage index and LV diastolic function has not been studied. Eighty-two SLE patients and 82 controls matched for age, sex, body mass index, blood pressure and heart rate underwent echocardiography with tissue Doppler imaging (TDI). LV diastolic function was estimated by the myocardial early diastolic velocity (E') at the lateral annulus. There were 51 patients (62.2%) with nephritis, 23 patients (28.0%) with hypertension, 21 patients (25.6%) with vasculitis, 16 patients (19.5%) with pulmonary hypertension, 4 patients (4.9%) with cerebrovascular disease and 2 patients (2.4%) with diabetes mellitus. Sixty-two patients (75.6%) were taking prednisone and 35 patients (42.7%) used a immunosuppressant. Forty-five patients (54.8%) had active disease and suffered from disease-related end-organ damage. Patients with SLICC/ACR damage index ≥1 had more evidence of LV diastolic dysfunction with lower lateral annulus E' (9.6 ± 3.4 vs 12.9 ± 3.5 cm/s, p < 0.001) than those without. In addition, the proportion of patients with abnormal LV myocardial relaxation (defined as lateral E' < 10.0 cm/s) (51.1% vs 16.2%, χ(2) = 10.8, p = 0.001) were significantly higher. Multivariate analysis showed that the SLICC/ACR damage index ≥1 was independently associated with LV diastolic dysfunction (OR = 3.80, 95%CI: 1.21-11.95, p = 0.023) after adjusting for hypertension, disease duration and medical therapy. This may suggest that the overall inflammatory burden in SLE, as reflected by SLICC/ACR damage index, is associated with the development of diastolic dysfunction in SLE patients.
[show abstract][hide abstract] ABSTRACT: To ascertain the effect of rosuvastatin on carotid atherosclerosis and arterial stiffness in patients with rheumatoid arthritis (RA).
Fifty RA patients were randomized in a double-blind placebo-controlled trial to receive 10 mg rosuvastatin (n = 24) or placebo (n = 26). Patients were followed prospectively every 3 months for 12 months. Intima-media thickness (IMT), augmentation index (AIx), and subendocardial viability ratio (SEVR) were measured at baseline, 6 and 12 months.
Rosuvastatin resulted in statistically significant reductions of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), apolipoprotein B (Apo B), and urate levels vs. placebo. However, rosuvastatin had no significant effect on changes in inflammatory markers, including C-reactive protein (CRP) levels [from 2.9 (1.4-11.0) to 3.1 (0.9-13.3) mg/L in the rosuvastatin group compared with from 5.8 (2.6-14.2) to 4.4 (1.2-12.3) mg/L in the placebo group]. Nonetheless, a significant improvement in the Disease Activity Score (DAS) and a reduction in fibrinogen level was observed at 6 and 12 months compared with baseline in the rosuvastatin group. The treatment group exhibited a significant increase in SEVR (from 157 ± 28% to 163 ± 33% in the rosuvastatin group compared with from 143 ± 18% to 143 ± 26% in the placebo group, p = 0.023), but no significant effect was observed in the changes in IMT and AIx.
Our data suggest that rosuvastatin has a modest anti-inflammatory effect in RA patients with low disease activity in terms of reduction in DAS and fibrinogen level. Rosuvastastin may also improve subendocardial perfusion and lower the urate level.
Scandinavian journal of rheumatology 08/2011; 40(6):411-21. · 2.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: Left atrial appendage (LAA) is the main source of left atrial thrombus that causes stroke in patients with non-valvular atrial fibrillation (NVAF). This study reported the initial safety, feasibility, and 1-yr clinical outcomes following AMPLATZER cardiac plug (ACP) implantation in Asia-Pacific region.
Twenty NVAF patients (16 males, age 68 ± 9 yr) with high risk for developing cardioembolic stroke (CHADS(2) score: 2.3 ± 1.3) and contraindications to warfarin received ACP implants from June 2009 to May 2010. Patients received general anesthesia (n = 9) or controlled propofol sedation (n = 11) and the procedures were guided by fluoroscopy and transesophageal echocardiography (TEE). Clinical follow-up was arranged at 1 month and then every 3 months after implantation, whereas, a TEE was scheduled at 1 month upon completion of dual anti-platelet therapy.
The LAA was successfully occluded in 19/20 patients (95%) at two Asian centers. One procedure was abandoned because of catheter-related thrombus formation. Other complications included coronary artery air embolism (n = 1) and TEE-attributed esophageal injury (n = 1). The median procedural and fluoroscopic times were 79 (IQR: 59-100) and 18 (IQR 12-27) minutes, respectively. The mean size of implant was 23.6 ± 3.1 mm. The average hospital stay was 1.8 ± 1.1 days. Follow-up TEE showed all the LAA orifices were sealed without device-related thrombus formation. No stroke or death occurred at a mean follow-up of 12.7 ± 3.1 months.
Our preliminary data suggested LAA closure with ACP is safe, feasible with encouraging 1-yr clinical outcomes. Further large-scaled trials are needed to confirm the efficacy of this device.
Catheterization and Cardiovascular Interventions 05/2011; 79(5):794-800. · 2.51 Impact Factor
[show abstract][hide abstract] ABSTRACT: Right ventricular apex (RVA) pacing may have deleterious effects on left ventricular (LV) systolic function, but its impact on LV diastolic function has not been explored.
Ninety-seven patients with sinus node dysfunction and ejection fraction (EF) ≥ 50% with permanent RVA pacing were randomly programmed to V-sense and V-pace modes and examined by echocardiography. Tissue Doppler imaging was employed to assess myocardial systolic velocity (S') and early diastolic velocity (E') at the mitral annulus. Systolic dyssynchrony was assessed using 12 LV segmental model (Ts-SD). Switching from V-sense to V-pace resulted in the worsening of both diastolic and systolic functions as shown by the decreased EF, reduced mean E' and S' velocities, as well as increase in LV volume and Ts-SD (all P< 0.001). Reduction of mean E' and S' of ≥ 1 cm/s occurred in 35 (36%) and 45 (46%) patients, respectively. In pre-defined subgroup analysis, only patients with pre-existing LV diastolic dysfunction had a significant reduction of mean E' and S' (both P< 0.001) even after age adjustment. Multivariate logistic regression analysis showed that independent factors for the reduction of mean E' ≥ 1 cm/s or mean S' ≥ 1 cm/s at V-pace were pre-existing LV diastolic dysfunction [odds ratio (OR): 4.735, P= 0.007 for E'; OR: 3.307, P= 0.022 for S'] and systolic dyssynchrony at V-pace (OR: 5.459, P= 0.007 for E'; OR: 2.725, P= 0.035 for S').
In patients with preserved EF, RVA pacing is associated with the deterioration of both LV diastolic and systolic functions, which is particularly obvious in those with pre-existing LV diastolic dysfunction and V-pace-induced systolic dyssynchrony.
European Heart Journal 04/2011; 32(15):1891-9. · 14.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Rho/rho-kinase (ROCK) pathway has an important role in the pathogenesis of several cardiovascular diseases. The activation of ROCK is involved in the regulation of vascular tone, endothelial dysfunction, inflammation and remodeling. The inhibition of ROCK has a beneficial effect in a variety of cardiovascular disorders. Evidence from animal models and from clinical use of ROCK inhibitors, such as Y-27632, fasudil and statins (i.e. pleiotropic effects), supports the hypothesis that ROCK is a potential therapeutic target. This review provides a current understanding of the role of ROCK pathway in the regulation of vascular function and the use of ROCK inhibitors in the treatment of cardiovascular disorders.
Drug discovery today 08/2010; 15(15-16):622-9. · 6.63 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study aimed to evaluate the impact of cardiac contractility modulation (CCM) on left ventricular (LV) size and myocardial function.
CCM is a device-based therapy for patients with advanced heart failure. Previous studies showed that CCM improved symptoms and exercise capacity; however, comprehensive assessment of LV structure, function, and reverse remodeling is not available.
Thirty patients (60 + or - 11 years, 80% male) with New York Heart Association (NYHA) functional class III heart failure, ejection fraction <35%, and QRS <120 ms were assessed at baseline and 3 months. LV reverse remodeling was measured by real-time 3-dimensional echocardiography. Using tissue Doppler imaging, the peak systolic velocity (Sm) and peak early diastolic velocity (Em) were calculated for LV function, while the standard deviation of the time to peak systolic velocity (Ts-SD) and the time to peak early diastolic velocity (Te-SD) were calculated for mechanical dyssynchrony.
LV reverse remodeling was evident, with a reduction in LV end-systolic volume by -11.5 + or - 10.5% and a gain in ejection fraction by 4.8 + or - 3.6% (both p < 0.001). Myocardial contraction was improved in all LV walls, including sites remote from CCM delivery (all p < 0.05); hence, the mean Sm of 12 (2.2 + or - 0.6 cm/s vs. 2.5 + or - 0.7 cm/s) or 6 basal LV segments (2.5 + or - 0.6 cm/s vs. 3.0 + or - 0.7 cm/s) were increased significantly (both p < 0.001). In contrast, CCM had no impact on regional or global Em (2.9 + or - 1.3 cm/s vs. 2.9 + or - 1.1 cm/s), whereas Ts-SD (28.2 + or - 11.2 ms vs. 27.9 + or - 12.7 ms) and Te-SD (30.0 + or - 18.3 ms vs. 30.1 + or - 20.7 ms) remained unchanged (all p = NS). Mitral regurgitation was reduced (22 + or - 14% vs. 17 + or - 15%, p = 0.02). Clinically, there was improvement of NYHA functional class (p < 0.001) and 6-min hall walk distance (p = 0.015). A 24-h Holter monitor showed that premature ventricular contractions were not increased during CCM.
CCM improves both global and regional LV contractility, including regions remote from the impulse delivery, and may contribute to LV reverse remodeling and gain in systolic function. Such improvement is unrelated to diastolic function or mechanical dyssynchrony.
[show abstract][hide abstract] ABSTRACT: To examine the predictive value of systolic dyssynchrony measured by tissue Doppler velocity versus tissue Doppler strain imaging on long-term outcome after cardiac resynchronisation therapy (CRT).
Two university hospitals.
Two hundred and thirty-nine patients (65 (SD 12) years, 76% males) who underwent CRT.
Baseline echocardiography with tissue Doppler imaging (TDI) and clinical follow-up for 37 (20) months.
The time to peak systolic velocity during ejection phase (Ts) and the time to peak systolic strain (T(epsilon)) were assessed for dyssynchrony, that is the maximal delay in Ts and the maximal delay in T(epsilon) among the four left ventricular basal segments. Occurrence of cardiovascular endpoints between patients with and without dyssynchrony was compared by Kaplan-Meier curves, followed by Cox regression analysis for potential predictor(s).
There were 78 (33%) deaths, with cardiovascular causes in 64 (27%) patients, while 136 (57%) patients were hospitalised for cardiovascular events, including decompensated heart failure in 87 (36%) patients. Patients with the maximal delay in Ts of > or =65 ms showed a lower event rate for cardiovascular mortality (19% vs 38%, logrank chi2 = 7.803, p = 0.005) and other prognostic endpoints. In Cox regression analysis, the maximal delay in Ts (hazard ratio (HR) 0.463, 95% CI 0.270 to 0.792, p = 0.005) and ischaemic aetiology (HR 2.716, 95% CI 1.505 to 4.901, p = 0.001) were independent predictors of cardiovascular mortality. In contrast, the maximal delay in T(epsilon) of > or =80 ms failed to predict any cardiovascular event.
Echocardiographic evidence of prepacing systolic dyssynchrony measured by TDI velocity, but not TDI strain, predicted lower long-term cardiovascular events after CRT.
[show abstract][hide abstract] ABSTRACT: To examine the impact of heart failure (HF) aetiology on long-term outcome after cardiac resynchronisation therapy (CRT).
Prospective cohort study.
119 patients (44% with ischaemic and 56% non-ischaemic aetiology) who underwent CRT.
Clinical follow-up for 39 (24) months.
Cardiovascular mortality, HF and cardiovascular hospitalisation were compared by Kaplan-Meier curves between the two groups, followed by Cox regression analysis for prognostic predictor(s).
41 (34%) patients died, in whom cardiovascular causes were identified in 32 (27%) patients. The ischaemic group had a higher cardiovascular mortality (log-rank chi(2) = 4.293, p = 0.038) and cardiovascular hospitalisation (log-rank chi(2) = 5.123, p = 0.024) when compared with the non-ischaemic group, though no difference was found in HF hospitalisation (log-rank chi(2) = 0.019, p = 0.892). At three months, left ventricular reverse remodelling occurred in 52% of the ischaemic group and 55% of the non-ischaemic group (chi(2) = 0.128, p = 0.720). By Cox regression analysis, ischaemic aetiology and absence of reverse remodelling at three months were independent predictors of cardiovascular mortality (HR = 2.698, p = 0.032; HR = 3.541, p = 0.030) and cardiovascular hospitalisation (HR = 1.905, p = 0.015; HR = 2.361, p = 0.004). Furthermore, these two factors had an incremental value in predicting cardiovascular mortality when compared with either alone (left ventricular reverse remodelling, log-rank chi(2) = 10.275 vs 6.311, p = 0.05; Ischaemic aetiology, log-rank chi(2) = 10.275 vs 4.293, p<0.05).
Ischaemic aetiology of HF is an independent predictor of higher cardiovascular mortality and hospitalisation after CRT. This may implicate the progressive nature of coronary heart disease leading to a worse outcome despite similar short-term benefits of CRT.
[show abstract][hide abstract] ABSTRACT: Arterial stiffness is an important index for cardiovascular events. The objective of this study is to examine possible parameters related to arterial stiffness that can be estimated during simple arm movements. An experiment was conducted on 32 subjects divided into two groups, one with an age of 26+/-4 years old, and the other 61+/-9. The pulse transit time measured from electrocardiogram to finger photoplethysmogram (PPG) and the amplitude of PPG were calculated beat-to-beat for the subjects while they had their arms lowered. The results of the study showed that the ratio between percentage changes in PTT and finger height are significantly different for the two groups of subjects with different age and health conditions, indicating that parameters can be potentially extracted from this procedure to represent the difference in arterial stiffness of the two groups of subjects.
Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 01/2009; 2009:1789-91.
[show abstract][hide abstract] ABSTRACT: The optimal left ventricular (LV) pacing site for cardiac resynchronization therapy (CRT) is unclear. The current study aims to explore the clinical significance of LV lead concordance to delayed contraction segment in CRT.
Concordant LV lead position was defined as the lead tip located by fluoroscopy at or immediately adjacent to the LV segment with latest contraction determined by tissue Doppler imaging. Echocardiographic and clinical outcomes among 101 consecutive patients with or without concordant LV lead positions were compared. There was no significant difference in changes in LV volumes and clinical parameters between patients with concordant (n = 46) or nonconcordant (n = 55) LV lead positions at 3 and 6 months. In multivariate analysis, the baseline asynchrony index (beta= 1.092, 95% CI: 1.050-1.114; P < 0.001), but not LV lead concordance, was the only independent predictor of LV reverse remodeling. By Cox regression analysis, ischemic etiology, and LV reverse remodeling, but not LV lead concordance, were independent predictors of mortality (beta= 2.475, 95% CI: 1.183-5.178; P = 0.016, and beta= 0.272, 95% CI: 0.130-0.567; P < 0.001, respectively), cardiovascular hospitalization (beta= 1.551, 95% CI: 1.032-2.333; P = 0.035, and beta= 0.460, 95% CI: 0.298-0.708; P < 0.001, respectively), and heart failure hospitalization (beta= 0.486, 95% CI: 0.320-0.738; P = 0.001 for LV reverse remodeling).
LV lead concordance to the delayed contraction segment may not be a major determining factor for favorable echocardiographic and clinical outcomes after CRT.
Journal of Cardiovascular Electrophysiology 12/2008; 20(5):530-5. · 3.48 Impact Factor
[show abstract][hide abstract] ABSTRACT: The pathological myocardial hypertrophy associated with hypertension contains the seed for further maladaptive development. Increased myocardial oxygen consumption, impaired epicardial coronary perfusion, ventricular fibrosis and remodelling, abnormalities in long-axis function and torsion, cause, to a varying degree, a mixture of systolic and diastolic abnormalities. In addition, chronotropic incompetence and peripheral factors such as lack of vasodilator reserve and reduced arterial compliance further affect cardiac output particularly on exercise. Many of these factors are common to hypertensive heart failure with a normal ejection fraction as well as systolic heart failure. There is increasing evidence that these apparently separate phenotypes are part of a spectrum of heart failure differing only in the degree of ventricular remodelling and volume changes. Furthermore, dichotomizing heart failure into systolic and diastolic clinical entities has led to a paucity of clinical trials of therapies for heart failure with a normal ejection fraction. Therapies aimed at reversing myocardial fibrosis, and targets outside the heart such as enhancing vasodilator reserve and improving chronotropic incompetence deserve further study and may improve the exercise capacity of hypertensive heart failure patients. Hypertension heart disease with heart failure is simply not a dysfunction of systole and diastole. Other peripheral factors including heart rate and vasodilator response with exercise may deserve equal attention in an attempt to develop more effective treatments for this disorder.
Journal of human hypertension 12/2008; 23(5):295-306. · 2.80 Impact Factor
[show abstract][hide abstract] ABSTRACT: Sibutramine is an amphetamine-like drug used for its weight reducing effect. Sibutramine-induced acute coronary syndrome has rarely been reported. We report a case of myocardial infarction associated with the use of sibutramine.
A 37-year-old woman presented to an Emergency Department (ED) with intermittent retrosternal chest pain, nausea, and sweating for 3 days. She reported taking one sibutramine tablet each day for 3 days. Blood pressure was 128/89 mm Hg and pulse 66 beats/min. An electrocardiogram revealed ST elevation over the inferior leads and ST depression over leads AVR and V1, the other leads were normal. Serum troponin T was 0.65 microg/L, and sibutramine was identified in her urine. Echocardiography revealed mild hypokinesia over the inferior wall without evidence of acute aortic dissection. The ST segment changes resolved spontaneously within 24 h of cardiac care unit (CCU) admission, a coronary angiogram performed 1 week later was unremarkable, and echocardiography performed 4 weeks after the event showed normal resting regional wall motion.
Seventeen medications containing sibutramine as an active ingredient were registered in Hong Kong in 2007. Sibutramine was introduced in the United States in 1997 and in Australia, United Kingdom, and Italy in 2001. Hypertension, tachycardia, dry mouth, and headache are the most commonly reported adverse reactions. Cardiovascular toxicities include tachycardia, palpitation, hypertension, and tachyarrhythmia.
We postulate that the myocardial infarction was the result of coronary vasospasm associated with the therapeutic use of sibutramine-containing slimming pills.
[show abstract][hide abstract] ABSTRACT: Although heart failure with a preserved or normal ejection fraction (HFNEF or diastolic heart failure) is common, treatment outcomes on quality of life and cardiac function are lacking. The effect of renin-angiotensin blockade by irbesartan or ramipril in combination with diuretics on quality of life (QoL), regional and global systolic and diastolic function was assessed in HFNEF patients.
150 patients with HFNEF (LVEF >45%) were randomised to (1) diuretics alone, (2) diuretics plus irbesartan, or (3) diuretics plus ramipril. QoL, 6-minute walk test (6MWT) and Doppler echocardiography were performed at baseline, 12, 24 and 52 weeks.
The QoL score improved similarly in all three groups by 52 weeks (-46%, 51%, and 50% respectively, all p<0.01), although 6MWT increased only slightly (average +3-6%). Recurrent hospitalisation rates were equal in all groups (10-12% in 1 year). At 1 year, LV dimensions or LVEF had not changed in any group, though both systolic and diastolic blood pressures were lowered in all three groups from 4 weeks onwards. At baseline both mean peak systolic (Sm) and early diastolic (Em) mitral annulus velocities were reduced, and increased slightly in the diuretic plus irbesartan (Sm 4.5 (SEM 0.17) to 4.9 (SEM 0.16) cm/sec; Em 3.8 (SEM 0.25) to 4.2 (SEM 0.25) cm/sec) and ramipril (Sm 4.5 (SEM 0.24) to 4.9 (SEM 0.20) cm/sec; Em 3.3 (SEM 0.25) to 4.04 (SEM 0.32) cm/sec) groups (both p<0.05). NT-pro-BNP levels were raised at baseline (595 (SD 905) pg/ml; range 5-4748) and fell in the irbesartan (-124 (SD 302) pg/ml, p = 0.01) and ramipril (-173 (SD 415) pg/ml, p = 0.03) groups only.
In this typically elderly group of HF patients with normal LVEF, diuretic therapy significantly improved symptoms and neither irbesartan nor ramipril had a significant additional effect. However, diuretics in combination with irbesartan or ramipril marginally improved LV systolic and diastolic longitudinal LV function, and lowered NT-proBNP over 1 year.
[show abstract][hide abstract] ABSTRACT: Left atrial (LA) volume is a predictor of cardiovascular events in patients with heart failure. Improvement of LA function and reverse remodeling was observed after cardiac resynchronization therapy (CRT).
The purpose of this study was to explore the clinical significance of improvement in LA function after CRT.
Echocardiographic studies were performed before and 3 months after CRT in 97 patients (72 men and 25 women; age 63.8 +/- 13.3 years) with standard CRT indication but no history of atrial fibrillation (AF). LA active emptying fraction based on the change in volumes (LAV-EF) were calculated, and significant improvement in LA function (LA responder) was defined as a relative increase >/=50% from baseline LAV-EF. The primary end-points were newly developed AF detected by ECG or device and all-cause mortality.
After 1,200 +/- 705 days of follow-up, LA responders (n = 47 [48.5%]) had a significantly lower incidence of AF (12.8% vs 40%, P = .002) and mortality (17% vs 44%, P = .004) than did LA nonresponders. In Cox proportional hazard analysis, LA responders was the only independent predictor of lower risk of new-onset AF (hazard ratio 0.22, 95% confidence interval 0.08-0.61, P = .003), whereas both LA responders (hazard ratio 0.22, 95% confidence interval 0.09-0.53, P <.001) and left ventricular reverse remodeling (>10% reduction in left ventricular end-systolic volume at 3 months; hazard ratio 0.96, 95% confidence interval 0.93-0.99, P = .03) were independent predictors of lower risk of death after CRT.
Improvement of LA function after CRT was associated with a lower incidence of AF and mortality in AF naïve patients with severe heart failure.
Heart rhythm: the official journal of the Heart Rhythm Society 06/2008; 5(6):780-6. · 4.56 Impact Factor