Kai-Hang Yiu

New‐Onset Heart Failure After Permanent Right Ventricular Apical Pacing in Patients with Acquired High‐Grade Atrioventricular Block and Normal Left Ventricular Function

Introduction: Emerging data have suggested that right ventricular (RV) apical pacing results in progressive left ventricular (LV) dysfunction and contributes to the development of heart failure (HF). This study aimed to investigate the prevalence and clinical predictors for the development of new‐onset HF after long‐term RV apical pacing in patients with acquired atrioventricular (AV) block who require permanent pacing.

Vitamin D Deficiency Is Associated with Depletion of Circulating Endothelial Progenitor Cells and Endothelial Dysfunction in Patients with Type 2 Diabetes

CONTEXT Vitamin D (Vit-D) deficiency is associated with type 2 diabetes mellitus (DM) and endothelial dysfunction. The relationship of Vit-D deficiency with circulating endothelial progenitor cells and endothelial dysfunction in type 2 DM patients nonetheless remains unclear. OBJECTIVE We aimed to investigate the cross-sectional association of Vit-D status with brachial flow-mediated dilation (FMD) and circulating endothelial progenitor cell (EPC) numbers in type 2 DM patients. DESIGN, SETTING, AND PARTICIPANTS We conducted a cross-sectional study of 280 patients (59% male, aged 68 ± 10 yr) with type 2 DM recruited in outpatient clinics during the winter period. MAIN OUTCOME MEASURE We measured serum 25-hydroxyvitamin D [25(OH)D] by an ELISA kit, circulating CD34+/kinase insert domain-containing receptor (KDR)+ and CD133+/KDR+ EPCs by flow cytometry and brachial artery FMD by vascular ultrasound, respectively. RESULTS The mean serum 25(OH)D concentration was 25.00 ± 9.17 ng/ml, and 34.3% of patients had Vit-D deficiency [25(OH)D < 20 ng/ml]. Serum 25(OH)D concentration had a significant correlation with hemoglobin A1c level [B = -0.018, 95% confidence interval (CI) -0.035 to -0.002, P = 0.032]. Patients with Vit-D deficiency status had significantly lower brachial FMD (mean difference -1.43%, 95% CI -2.31 to -0.55, P = 0.001) and CD133+/KDR+EPC counts (mean difference -0.12%, 95% CI -0.21 to -0.019, P = 0.022) than those with sufficient Vit-D status after adjustment for age, sex, and cardiovascular risk factors, including hemoglobin A1c levels. CONCLUSIONS Our results demonstrate that serum 25(OH)D status was significantly associated with brachial artery FMD and circulating CD133+/KDR+EPCs. This suggests that Vit-D deficiency might contribute to depletion of EPCs and endothelial dysfunction in patients with type 2 DM.

Burden of carotid atherosclerosis in patients with stroke: relationships with circulating endothelial progenitor cells and hypertension

Recent studies suggest that reductions in circulating endothelial progenitor cells (EPCs) may contribute to the development of atherosclerosis. However, whether reduced circulating EPCs contribute to cerebrovascular disease remains undefined. We tested the hypothesis that reduced circulating EPCs was associated with an increased burden of carotid atherosclerosis. The level of circulating CD34+/KDR+ EPCs and the extent of carotid atherosclerosis were determined in 30 patients with a history of atherothrombotic ischaemic stroke and 30 age- and sex-matched controls (mean age: 63±2 years; 63% men). Stroke patients, compared with controls, had significantly higher carotid mean maximum intima-media thickness (mmIMT) (1.08±0.05 versus 0.90±0.02 mm, P=0.002), prevalence of carotid plaque (60.0 versus 23.3%, P=0.004) and a lower number of circulating CD34+/KDR+ EPCs (235.7±45.5 versus 400.4±56.8 cells/μl, P=0.027). The circulating CD34+/KDR+ EPC count correlated negatively with carotid mmIMT (r=−0.50, P<0.001), and was an independent risk factor for increased carotid mmIMT>1 mm (odds ratio (OR): 7.71; 95% confidence interval (CI): 1.62–36.74, P=0.010) and the presence of carotid plaque (OR: 7.04; 95% CI: 1.95–25.43, P=0.003). Furthermore, stroke patients with low (<25th percentile of controls) as compared to those with normal CD34+/KDR+ EPC count had a significantly greater carotid mmIMT (1.21±0.07 versus 0.93±0.05 mm, P=0.005) and a significantly higher prevalence of carotid plaque (87.5% versus 28.6%; P=0.001). Our observations suggested that reduced circulating EPC may contribute to the progression of carotid atherosclerosis. Circulating EPC count may provide a novel marker for the burden of carotid atherosclerosis.

Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke.

AIMS To investigate the effect of oral isoflavone supplement on vascular endothelial function in patients with established cardiovascular disease. METHODS AND RESULTS A randomized, double-blinded, placebo-controlled trial was performed to determine the effects of isoflavone supplement (80 mg/day, n = 50) vs. placebo (n = 52) for 12 weeks on brachial flow-mediated dilatation (FMD) in patients with prior ischaemic stroke. Compared with controls, FMD at 12 weeks was significantly greater in isoflavone-treated patients [treatment effect 1.0%, 95% confidence interval (95% CI) 0.1-2.0, P = 0.035]. Adjusted for baseline differences in FMD, isoflavone treatment was independently associated with significantly less impairment of FMD at 12 weeks (odds ratio 0.32, 95% CI 0.13-0.80, P = 0.014). The absolute treatment effect of isoflavone on brachial FMD was inversely related to baseline FMD (r = -0.51, P < 0.001), suggesting that vasoprotective effect of isoflavone was more pronounced in patients with more severe endothelial dysfunction. Moreover, isoflavone treatment for 12 weeks resulted in a significant decrease in serum high-sensitivity (hs)-C-reactive protein level (treatment effect -1.7 mg/L, 95% CI -3.3 to -0.1, P = 0.033). Nevertheless, isoflavone did not have any significant treatment effects on nitroglycerin-mediated dilatation, blood pressure, heart rate, serum levels of fasting glucose and insulin, haemoglobin A1c, and oxidative stress as determined by serum superoxide dismutase, 8-isoprostane, and malondialdehyde (all P > 0.05). CONCLUSION This study demonstrated that 12 week isoflavone treatment reduced serum hs-C-reactive protein and improved brachial FMD in patients with clinically manifest atherosclerosis, thus reversing their endothelial dysfunction status. These findings may have important implication for the use of isoflavone for secondary prevention in patients with cardiovascular disease, on top of conventional interventions.

Impact of glycemic control on circulating endothelial progenitor cells and arterial stiffness in patients with type 2 diabetes mellitus

BackgroundPatients with type 2 diabetes mellitus (DM) have increased risk of endothelial dysfunction and arterial stiffness. Levels of circulating endothelial progenitor cells (EPCs) are also reduced in hyperglycemic states. However, the relationships between glycemic control, levels of EPCs and arterial stiffness are unknown.MethodsWe measured circulating EPCs and brachial-ankle pulse wave velocity (baPWV) in 234 patients with type 2 DM and compared them with 121 age- and sex-matched controls.ResultsPatients with DM had significantly lower circulating Log CD34/KDR+ and Log CD133/KDR+ EPC counts, and higher Log baPWV compared with controls (all P < 0.05). Among those 120/234 (51%) of DM patients with satisfactory glycemic control (defined by Hemoglobin A1c, HbA1c < 6.5%), they had significantly higher circulating Log CD34/KDR+ and Log CD133/KDR+ EPC counts, and lower Log baPWV compared with patients with poor glycemic control (all P < 0.05). The circulating levels of Log CD34/KDR+ EPC (r = -0.46, P < 0.001) and Log CD133/KDR+ EPC counts (r = -0.45, P < 0.001) were negatively correlated with Log baPWV. Whilst the level of HbA1c positively correlated with Log baPWV (r = 0.20, P < 0.05) and negatively correlated with circulating levels of Log CD34/KDR+ EPC (r = -0.40, P < 0.001) and Log CD133/KDR+ EPC (r = -0.41, P < 0.001). Multivariate analysis revealed that HbA1c, Log CD34/KDR+ and Log CD133/KDR+ EPC counts were independent predictors of Log baPWV (P < 0.05).ConclusionsIn patients with type 2 DM, the level of circulating EPCs and arterial stiffness were closely related to their glycemic control. Furthermore, DM patients with satisfactory glycemic control had higher levels of circulating EPCs and were associated with lower arterial stiffness.

Effect of exercise training on vascular endothelial function in patients with stable coronary artery disease: a randomized controlled trial.

Background: We aim to investigate the effect of exercise training on endothelial function and exercise capacity in patients with coronary artery disease. Methods and results: A randomized, controlled trial was conducted to determine the effects of an 8-week exercise training programme (n = 32) vs. controls (n = 32) on brachial flow-mediated dilation (FMD) in patients with stable CAD. After 8 weeks, patients received exercise training had significant improvements in FMD (1.84%, p = 0.002) and exercise capacity (2.04 metabolic equivalents, p < 0.001) compared with controls. The change in FMD correlated inversely with baseline FMD (r = −0.41, p = 0.001) and positively with the increase in exercise capacity (r = 0.35, p = 0.005). After adjusting for confounders, every 1 metabolic equivalent increase in exercise capacity was associated with 0.55% increase in FMD. Furthermore, patients received exercise training had significantly increased high-density lipoprotein cholesterol and decreased diastolic blood pressure and resting heart rate compared with controls. However, exercise training did not alter high-sensitivity C-reactive protein, oxidative stress measured as superoxide dismutase and 8-isoprostane, and CD34/KDR + endothelial progenitor cell count. Subgroup analysis showed that FMD was significantly improved only in CAD patients with baseline low exercise capacity (<median value of 7.65 metabolic equivalents, p = 0.004) but not in those with normal exercise capacity. Conclusion: Exercise training improved FMD and exercise capacity in stable CAD patients independent of the changes in inflammation, oxidative stress, or endothelial progenitor cells. The beneficial effects of exercise training on FMD and exercise capacity are inter-related, and more pronounced in those with baseline impaired exercise capacity.

Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation.

Background  Psoriasis is associated with premature atherosclerosis although the underlying mechanism remains unclear.

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: A randomized controlled trial

AIMS Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). CONCLUSION In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD.

Prevalence and extent of calcification over aorta, coronary and carotid arteries in patients with rheumatoid arthritis

Objective.  To evaluate the prevalence and pattern of arterial calcification in patients with rheumatoid arthritis (RA).

Thoracic Spinal Cord Stimulation for Heart Failure as a Restorative Treatment (SCS HEART study): first-in-man experience

BACKGROUND Preclinical studies suggest that neuromodulation with thoracic spinal cord stimulation (SCS) improves left ventricular (LV) function and remodeling in systolic heart failure (HF). OBJECTIVE The purpose of this study was to evaluate the safety and efficacy of a SCS system for the treatment of systolic HF. METHODS We performed a prospective, multicenter pilot trial in patients with New York Heart Association (NYHA) class III HF, left ventricular ejection fraction (LVEF) 20%-35%, and implanted defibrillator device who were prescribed stable optimal medical therapy. Dual thoracic SCS leads were used at the T1-T3 level. The device was programmed to provide SCS for 24 hours per day (50 Hz at pulse width 200 μs). RESULTS We enrolled 22 patients from 5 centers:17 patients underwent implantation of a SCS device and 4 patients who did not fulfill the study criteria served as nontreated controls. No deaths or device-device interactions were noted during the 6-month period in the 17 SCS-treated patients. Fifteen of 17 completed the efficacy endpoint assessments: composite score improved by 4.2 ± 1.3, and 11 patients (73%) showed improvement in ≥4 of 6 efficacy parameters. There was significant improvement in NYHA class (3.0 vs 2.1, P = .002; 13/17 improved); Minnesota Living with Heart Failure Questionnaire (42 ± 26 vs 27 ± 22, P = .026; 12/17 improved); peak maximum oxygen consumption (14.6 ± 3.3 vs 16.5 ± 3.9 mL/kg/min, P = .013; 10/15 improved); LVEF (25% ± 6% vs 37% ± 8%, P<.001; 14/16 improved); and LV end-systolic volume (174 ± 57 vs 137 ± 37 mL, P = .002; 11/16 improved) but not in N-terminal prohormone brain natriuretic peptide. No such improvements were observed in the 4 nontreated patients. CONCLUSION The results of this first-in-human trial suggest that high thoracic SCS is safe and feasible and potentially can improve symptoms, functional status, and LV function and remodeling in patients with severe, symptomatic systolic HF.