Aun-Yeong Chong

Endothelial Dysfunction and Damage in Congestive Heart Failure. Relation of Flow-Mediated Dilation to Circulating Endothelial Cells, Plasma Indexes of Endothelial Damage, and Brain Natriuretic Peptide

Background—Congestive heart failure (CHF) is associated with endothelial perturbation (as defined by flow-mediated endothelial-dependent vasodilation [FMD, an index of endothelial dysfunction], circulating endothelial cells [CECs, an index of endothelial damage], or plasma indexes of endothelial damage/dysfunction [eg, von Willebrand factor (vWf) and soluble thrombomodulin (sTM)]) and raised plasma levels of brain natriuretic peptide (BNP, a peptide hormone associated with left ventricular systolic dysfunction and prognosis). However, the relations between these parameters are unclear. Methods and Results—To test the hypothesis that there is a relation between endothelial perturbation (defined by FMD, CECs, vWf, and sTM) and BNP in CHF, we studied these indexes in 30 patients with CHF who were compared with 20 age-matched control subjects. FMD, CECs, plasma vWf, and BNP levels (but not sTM) were all abnormal in patients with CHF. There were significant inverse correlations between FMD and vWf (P=0.001), CECs (P=0.002) and BNP (P=0.006) as well as a positive correlation between CECs and vWf (P=0.032). In multivariate analysis, BNP (P<0.001) and FMD (P<0.001) were both independently associated with CHF. Conclusions—Ample evidence of endothelial cell damage/dysfunction in CHF cannot be fully explained by the variance in plasma BNP per se. Therefore, the routes by which these indexes influence the pathophysiology of CHF as well as predict adverse outcomes may be independent.

Impact of access site selection and operator expertise on radiation exposure; a controlled prospective study.

BACKGROUND Published data relating to arterial access site selection and radiation exposure during coronary procedures suggest radial access may lead to increased radiation exposure, but this is based on poorly controlled studies. We sought to measure radiation exposure to patients and operators during elective coronary angiography (CA) according to access site, with other procedure related variables controlled for. We also investigated the specific effect of operator expertise in relation to radiation exposure. METHODS 100 consecutive patients undergoing first time elective CA were recruited prospectively. An expert transradial (TR) and an expert transfemoral (TF) operator performed 25 cases each via their default route. A trainee cardiologist with intermediate experience in both access sites performed 25 cases via each route. Angiographic projections were standardised and optimised radiation protection was utilised for all procedures. The primary endpoints were operator and patient exposure, quantified by effective dose (ED) and dose area product (DAP) respectively. Secondary endpoints included fluoroscopy time (FT) and time to patient ambulation. RESULTS The trainee operator recorded higher values for radiation exposure in radial and femoral cases when compared to the expert operators. There were no significant differences in radiation exposure during CA to operator or patient according to access site when standardised by operator experience. For the trainee, ED for TR and TF procedures was 8.8 ± 4.3 μSv and 8.5 ± 6.5 μSv (P = .86) and DAP was 25.4 ± 4.8 Gycm(2) vs 25.2 ± 8.3 Gycm(2) (P = .9). For the expert TR and TF operators, ED was 6.4 ± 4.7 μSv vs 6.1 ± 5.6 μSv (P = .85) and DAP was 21.7 ± 6.5 Gycm(2) vs 22.4 ± 8.0 Gycm(2), (P = .74). There was no significant difference in FT in relation to access site. Time to ambulation was significantly longer with TF access. CONCLUSION The use of TR access has no adverse effect on radiation exposure or FT for diagnostic CA, but does allow for quicker ambulation compared to TF access. The magnitude of radiation exposure is related to operator expertise for both access sites. The results of previous studies reflect the effect of uncontrolled patient and operator variables and not access site selection.

Increased circulating endothelial cells in acute heart failure: comparison with von Willebrand factor and soluble E-selectin.

Circulating endothelial cells (CECs) in the peripheral blood, probably representing the most direct evidence of endothelial cell damage, are increased in myocardial infarction, unstable angina and critical limb ischaemia. As chronic heart failure is also associated with endothelial abnormalities, we hypothesised that CECs are raised in acute heart failure and that they would correlate with plasma indices of endothelial perturbation, that is, von Willebrand factor (vWf) and soluble E‐selectin.

Heart failure in a multiethnic population in Kuala Lumpur, Malaysia.

There are established differences in cardiovascular disease in different racial groups. Worldwide, the literature regarding the clinical epidemiology of congestive heart failure (CHF) in non‐white populations is scarce.

Viewpoint: The prothrombotic state in heart failure: A maladaptive inflammatory response?

Patients with heart failure (HF) are at an increased risk of stroke, sudden death and venous thromboembolism, which are all linked to thrombus formation (thrombogenesis). The present ‘viewpoint’ article will discuss how the prothrombotic state in HF may be perpetuated by a chronic inflammatory state that is maladaptive. Indeed, there is considerable evidence that thrombogenesis and endothelial (dys)function can be intimately linked to inflammation in HF.

Influence of Atrial Fibrillation on Plasma Von Willebrand Factor, Soluble E-Selectin, and N-Terminal Pro B-type Natriuretic Peptide Levels in Systolic Heart Failure

BACKGROUND Endothelial dysfunction is present in patients with heart failure (HF) due to left ventricular systolic dysfunction, as well as in patients with atrial fibrillation (AF) who have normal cardiac function. It is unknown whether AF influences the degree of endothelial dysfunction in patients with systolic HF. METHODS We measured levels of plasma von Willebrand factor (vWF) and E-selectin (as indexes of endothelial damage/dysfunction and endothelial activation, respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well as in age-matched, healthy, control subjects. We also assessed the relationship of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro-BNP), a marker for HF severity and prognosis. RESULTS One hundred ninety patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were studied, who were compared to 117 healthy control subjects: 52 subjects (27%) were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and New York Heart Association class were similar. There were significant differences in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels when compared to SR-HF patients. On multivariate analysis, the presence of AF was related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). CONCLUSIONS There is evidence of greater endothelial damage/dysfunction in AF-HF patients when compared to SR-HF patients. The clinical significance of this is unclear but may have prognostic value.

Angiogenic factors in atrial fibrillation : A possible role in thrombogenesis?

Background. The precise pathophysiological processes underlying the prothrombotic or hypercoagulable state in atrial fibrillation (AF) remain uncertain. We hypothesized a relationship between abnormal endothelial damage/dysfunction, coagulation, and angiogenic factors, thereby contributing to increased thrombogenicity. Methods. Plasma levels of von Willebrand factor (vWF, an index of endothelial damage/dysfunction) and tissue factor (TF, an index of coagulation), as well as the angiogenic factors, vascular endothelial growth factor (VEGF), angiopoietin‐1 (Ang‐1) and angiopoietin‐2 (Ang‐2), were measured by enzyme‐linked immunosorbant assay (ELISA) in 59 chronic AF patients. Data were compared to 40 age‐ and sex‐matched healthy controls in sinus rhythm. Results. Plasma vWF, VEGF and Ang‐2 were significantly higher in AF patients compared to healthy controls (P = 0.005, P = 0.0055 and P<0.0001 respectively) but there were no significant differences in plasma Ang‐1 or TF levels between the two groups (P = 0.925 and P = 0.121 respectively). Significant correlations were found between VEGF and vWF levels (Spearman, r = 0.262, P = 0.011) and between VEGF and Ang‐2 (r = 0.333, P = 0.001). Conclusions. Raised VEGF in association with Ang‐2 and vWF may reflect a link between abnormal endothelial damage/dysfunction and angiogenic factors. These may act together to alter TF expression and endothelial integrity, thereby contributing to the prothrombotic state in AF.

Prophylactic Warfarin Therapy After Primary Percutaneous Coronary Intervention for Anterior ST-Segment Elevation Myocardial Infarction

OBJECTIVES This study sought to determine the benefits of adding oral anticoagulation therapy in patients with anterior wall ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (PCI). BACKGROUND Guidelines suggest adding oral anticoagulation to dual-antiplatelet therapy in patients with STEMI when left ventricular apical akinesis or dyskinesis is present to prevent thromboembolic complications. The benefits of this triple therapy remain unknown. METHODS We identified patients with anterior STEMI referred (PCI) between July 2004 and June 2010 with apical akinesis or dyskinesis on transthoracic echocardiography. We compared patients who were prescribed warfarin to patients who were not. We excluded patients with left ventricular thrombus, a separate need for oral anticoagulation, and previous intracranial bleeding. The primary outcome was a composite of net adverse clinical events (NACE) consisting of all-cause mortality, stroke, reinfarction, and major bleeding at 180 days. RESULTS Among 460 patients who qualified, 131 were discharged on warfarin therapy and 329 without warfarin therapy. Dual-antiplatelet therapy was prescribed for 99.2% of the patients in the warfarin group and for 97.6% of the patients in the no warfarin group (p = 0.46). Compared with patients in the no warfarin group, patients in the warfarin group had higher rates of NACE (14.7% vs. 4.6%, p = 0.001), death (5.4% vs. 1.5%, p = 0.04), stroke (3.1% vs. 0.3%, p = 0.02), and major bleeding (8.5% vs. 1.8%, p < 0.0001). By propensity score analysis, allocation to warfarin therapy was an independent predictor of NACE (odds ratio [OR]: 4.01, 95% confidence interval: 2.15 to 7.50, p < 0.0001). In a separate multivariable analysis, the OR of NACE remained significantly higher compared with patients who were not prescribed warfarin (OR: 3.13, 95% confidence interval: 1.34 to 7.22, p = 0.007). CONCLUSIONS Our results do not support the addition of warfarin therapy after primary PCI in patients with apical akinesis or dyskinesis.

Performance of transcatheter aortic valve implantation in patients with bicuspid aortic valve: Systematic review

bicuspid aortic valve: Systematic review Altayyeb Yousef , Trevor Simard , Ali Pourdjabbar , John Webb , Derek So , Aun-Yeong Chong , Christopher Glover , Michel Le May , Benjamin Hibbert , Marino Labinaz a,⁎ a Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada b Division of Cardiology, St. Pauls Hospital, University of British Columbia, Vancouver, British Columbia, Canada

The effect of multi-factorial intervention on plasma von Willebrand factor, soluble E-selectin and tissue factor in diabetes mellitus: implications for atherosclerotic vascular disease

Background  Endothelial abnormalities and a hypercoagulable state may contribute to increased cardiovascular risk in diabetes mellitus, particularly in patients with overt cardiovascular disease (CVD). We sought to determine the effect of intensified multi‐factorial cardiovascular risk intervention on indices of endothelial abnormality and hypercoagulability in diabetes, and if patients with overt CVD would derive similar benefit as those without.