Stephen Wl Lee

The REMEDEE trial: a randomized comparison of a combination sirolimus-eluting endothelial progenitor cell capture stent with a paclitaxel-eluting stent.

OBJECTIVES This study sought to compare the efficacy and safety results after coronary implantation of a combined sirolimus-eluting CD34 antibody coated Combo stent (OrbusNeich Medical, Ft. Lauderdale, Florida) with the paclitaxel-eluting Taxus Liberté stent (PES) (Boston Scientific, Natick, Massachusetts). This report summarizes the first-in-man randomized, controlled multicenter REMEDEE trial (Randomized study to Evaluate the safety and effectiveness of an abluMinal sirolimus coatED bio-Engineered StEnt) angiographic, intravascular ultrasound, and clinical results up to 12 months. BACKGROUND Drug-eluting stents have limited restenosis and reintervention but are complicated by especially late and very late stent thrombosis and accelerated neoatherosclerosis. Alternative or adjunct technologies should address these limitations. METHODS One hundred eighty-three patients with de novo native coronary artery stenoses were randomized 2:1 to Combo stent or PES implantation. The primary endpoint is the angiographic in-stent late lumen loss at 9 months, which was tested for noninferiority between the 2 stent groups. Secondary endpoints include the occurrence of major adverse cardiac events. RESULTS The Combo stent was found to be noninferior to the PES in 9-month angiographic in-stent late lumen loss with 0.39 ± 0.45 mm versus 0.44 ± 0.56 mm (pnoninferiority = 0.0012). At 12 months, the occurrence of major adverse cardiac events was 8.9% in the Combo group and 10.2% in the PES group (p = 0.80) with no difference in mortality, occurrence of myocardial infarction, or target lesion revascularization. No stent thrombosis was reported in either group. CONCLUSIONS In the REMEDEE trial the Combo stent has shown to be effective by meeting the primary noninferiority angiographic endpoint and safe, with an overall low rate of clinical events in both stent groups, including no stent thrombosis up to 12 months.

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.

Fish-oil supplement has neutral effects on vascular and metabolic function but improves renal function in patients with Type 2 diabetes mellitus.

Diabet. Med. 27, 54–60 (2010)

Smoking Is Associated With Depletion of Circulating Endothelial Progenitor Cells and Elevated Pulmonary Artery Systolic Pressure in Patients With Coronary Artery Disease

Smoking is associated with depletion of endothelial progenitor cells (EPCs) and may subsequently contribute to the development of vascular dysfunction. The aim of this study was to investigate the relation between circulating EPCs and pulmonary artery systolic pressure (PASP) as determined by flow cytometry and echocardiography in 174 patients (mean age 69 ± 9 years, 95 smokers) with established coronary artery disease. Smokers had significantly lower circulating log CD34/KDR(+) (0.86 ± 0.03 vs 0.96 ± 0.03 × 10⁻³/ml, p = 0.032) and log CD133/KDR(+) (0.68 ± 0.03 vs 0.82 ± 0.03 × 10⁻³/ml, p = 0.002) EPCs and a higher prevalence of elevated PASP >30 mm Hg (52% vs 30%, p = 0.001) than nonsmokers. Smokers with elevated PASP also had significantly lower circulating log CD34/KDR(+) (0.74 ± 0.04 vs 0.88 ± 0.06 × 10⁻³/ml, p <0.001) and log CD133/KDR(+) (0.61 ± 0.04 vs 0.78 ± 0.05 × 10⁻³/ml, p <0.001) EPCs, higher pulmonary vascular resistance, and larger right ventricular dimensions with impaired function (all p values <0.05). Log CD34/KDR(+) and log CD133/KDR(+) EPC counts were significantly and negatively correlated with PASP (r = -0.30, p <0.001, and r = -0.34, p <0.001, respectively) and pulmonary vascular resistance (r = -0.29, p = 0.002, and r = -0.18, p = 0.013, respectively). In conclusion, this study demonstrated that in patients with coronary artery disease, smoking was associated with a reduced number of EPCs and elevated PASP. This suggests that in smokers, depletion of circulating EPCs might be linked to the occurrence of pulmonary vascular dysfunction.

Relationship between changes in heart rate recovery after cardiac rehabilitation on cardiovascular mortality in patients with myocardial infarction.

BACKGROUND Heart rate recovery (HRR) at predischarge exercise stress test predicts all-cause mortality in patients with myocardial infarction (MI), but the relationship between improvement in HRR with exercise training and clinical outcomes remains unclear. OBJECTIVE The purpose of this study was to evaluate the effect of change in HRR after exercise training on clinical outcomes in MI patients. METHODS The study included 386 consecutive patients with recent MI who were enrolled into our cardiac rehabilitation program. All patients underwent symptom-limited treadmill testing at baseline and after exercise training, and were prospectively followed-up in the outpatient clinic. RESULTS Treadmill testing revealed significant improvement in HRR after 8 weeks of exercise training (17.5 +/- 10.0 bpm to 19.0 +/- 12.3 bpm, P = .011). After follow-up of 79 +/- 41 months, 40 (10.4%) patients died of cardiac events. Multivariate Cox regression analysis revealed that diabetes (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.01-5.19, P = .049), statin use (HR 0.36, 95% CI 0.16-0.80, P = .012), baseline resting heart rate > or =65 bpm (HR 5.37, 95% CI 1.33-21.61, P = .018), post-training HRR <12 bpm (HR 2.49, 95% CI 1.10-5.63, P = .028), left ventricular ejection fraction < or =30% (HR 4.70, 95% CI 1.34-16.46, P = .016), and exercise capacity < or =4 metabolic equivalents (HR 3.63, 95% CI 1.17-11.28, P = .026) were independent predictors of cardiac death. Patients who failed to improve HRR from <12 bpm to > or =12 bpm after exercise training had significantly higher mortality (HR 6.2, 95% CI 1.3-29.2, P = .022). CONCLUSION Exercise training improved HRR in patients with recent MI, and patients with HRR increased to > or =12 bpm had better cardiac survival.

Global geographical variations in ST-segment elevation myocardial infarction management and post-discharge mortality

BACKGROUND There is a shortage of information on regional variations in ST-segment elevation myocardial infarction (STEMI) management and prognosis at a global level. We aimed to compare patient profiles, in-hospital management and post-discharge mortality across several world regions. METHODS In total, 11,559 patients with STEMI were enrolled in two prospective studies of acute coronary syndrome survivors: EPICOR (4943 patients from 555 hospitals in 20 countries in Europe and Latin America recruited between September 2010 and March 2011) and EPICOR Asia (6616 patients from 218 hospitals in eight Asian countries recruited between June 2011 and May 2012). Comparisons were performed by eight pre-defined regions: Northern Europe (NE), Southern Europe (SE), Eastern Europe (EE), Latin America (LA), China (CN), India (IN), Southeast Asia (SA), and South Korea/Hong Kong/Singapore (KS). RESULTS Reperfusion therapy rates ranged between 53.9% (IN) and 81.2% (SE), primary percutaneous coronary intervention (PCI) between 24.8% (IN) and 65.6% (NE) and fibrinolysis between 8.1% (CN) and 34.2% (SA). Median time to primary PCI (h) ranged from 3.9 (NE) to 20.9 (IN) and to fibrinolysis from 2.4 (SE) to 6.3 (IN). Two-year mortality ranged between 2.5% in NE and 7.4% in LA. Regional variations in mortality persisted after adjustment for reperfusion therapy and known prognostic factors. CONCLUSIONS Among patients with STEMI, there is a wide regional variation in clinical profiles, hospital care and mortality. Substantial room for improvement remains at a global level for increasing reperfusion rates, reducing delays and post-discharge mortality in patients with STEMI.

Rationale, Design, and Baseline Characteristics of the EPICOR Asia Study (Long‐tErm follow‐uP of antithrombotic management patterns In Acute CORonary Syndrome patients in Asia)

In‐hospital and postdischarge mortality for acute coronary syndromes (ACS) vary across Asia and remain generally poorer than globally. The relationship between real‐life antithrombotic management patterns (AMPs) and ACS‐related outcomes in Asia is unclear.

Characteristics and outcomes of medically managed patients with non-ST-segment elevation acute coronary syndromes: Insights from the multinational EPICOR Asia study

BACKGROUND Many patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) are medically managed without coronary revascularization. The reasons vary and may impact prognosis. METHODS EPICOR Asia (NCT01361386) is a prospective study of hospital survivors post-ACS enrolled in 218 hospitals from 8 countries/regions in Asia (06/2011-05/2012). All medically managed NSTE-ACS patients were classified into 3 groups: 1) no coronary angiography (CAG-); 2) non-significant coronary artery disease (CAD) on angiogram (CAG+ CAD-); and 3) significant CAD (CAG+ CAD+). We compared baseline differences between patients medically managed and patients undergoing revascularization, and also between the medically managed groups. Adverse events were reported and compared up to 2years. RESULTS Of 6163 NSTE-ACS patients, 2272 (37%) were medically managed, with 1339 (59%), 254 (11%), and 679 (30%) in the CAG-, CAG+ CAD-, and CAG+ CAD+ groups, respectively. There were marked differences in the proportion of medically managed patients among the 8 countries/regions (13-81%). Medically managed patients had higher mortality at 2years compared with revascularization (8.7% vs. 3.0%, p<0.001). Among medically managed patients, CAG- patients were older, more likely to have pre-existing cardiovascular disease, and had the highest 2-year mortality (10.5% vs. 4.3% [CAG+ CAD-] and 6.6% [CAG+ CAD+], p<0.001). Mortality differences persisted after adjusting for other patient risk factors. CONCLUSIONS Medically managed NSTE-ACS patients are a heterogeneous group with different risk stratification and variable prognosis. Identification of reasons underlying different management strategies, and key factors adversely influencing long-term prognosis, may improve outcomes.

Relationship between ventricular dyssynchrony and T-wave alternans in patients with coronary artery disease.

Introduction: Coronary artery disease (CAD) is associated with increased dispersion of repolarization and sudden cardiac death. We sought to investigate whether ventricular dyssynchrony is associated with proarrhythmic repolarization dispersion as measured by T‐wave alternans (TWA) in patients with CAD.

A 10-YEAR REVIEW OF THROMBOLYTIC THERAPY IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION IN A UNIVERSITY HOSPITAL IN HONG KONG – INTRACRANIAL BLEEDING AND OTHER OUTCOMES

Thrombolysis remains an important reperfusion strategy for eligible patients with acute ST-segment elevation myocardial infarction (STEMI). Intracranial bleeding is a potentially fatal complication. A total of 342 Patients who received thrombolytic therapy in a University Hospital in Hong Kong for