Kai-Hang Yiu

Queen Mary Hospital, Hong Kong, Hong Kong

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Publications (70)252.31 Total impact

  • Article: Impact of Valvuloarterial Impedance on 2-Year Outcome of Patients Undergoing Transcatheter Aortic Valve Implantation.
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    ABSTRACT: BACKGROUND: Elderly patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) often have increased calcification and fibrosis of the aorta. Indices that account for the severity of valvular obstruction and systemic vascular impedance may better assess total left ventricular afterload. The aims of the present study were to evaluate changes in valvuloarterial impedance (Zva), systemic arterial compliance, and systemic vascular resistance after TAVI and to investigate the prognostic value of these parameters. METHODS: A total of 116 patients (49% men; mean age, 81 ± 8 years) with symptomatic severe aortic stenosis underwent TAVI. Zva, systemic arterial compliance, and systemic vascular resistance were measured at baseline and 1 and 12 months after TAVI. The primary end point was all-cause mortality. RESULTS: After TAVI, there was a significant reduction in Zva (from 5.40 ± 1.52 mm Hg/mL/m(2) at baseline to 4.13 ± 1.17 mm Hg/mL/m(2) at 1 month and 4.35 ± 1.38 mm Hg/mL/m(2) at 1 year, P < .001). Systemic arterial compliance (from 0.57 ± 0.27 to 0.57 ± 0.28 and 0.53 ± 0.27 mL/m(2)/mm Hg, P = .408) and systemic vascular resistance (from 1,938 ± 669 to 1,856 ± 888 and 1,871 ± 767, dyne·s·cm(-5), P = .697) did not change significantly over time. During a median follow-up period of 25 months, survival rates of patients with baseline Zva ≥ 5 mm Hg/mL/m(2) were lower compared with those with Zva < 5 mm Hg/mL/m(2) (82% vs 91%, respectively, log-rank P = .04). On multivariate Cox proportional-hazards analysis, baseline Zva was independently associated with all-cause mortality (hazard ratio, 1.48; 95% confidence interval, 1.05-2.07; P = .025). CONCLUSIONS: In patients undergoing TAVI, there is a significant postprocedural reduction in Zva, but there is no reduction in systemic arterial compliance or vascular resistance. Baseline Zva is an independent predictor of overall mortality at 2-year follow-up.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 05/2013; · 2.98 Impact Factor
  • Article: Zotarolimus-eluting stent utilization in small-vessel coronary artery disease (ZEUS).
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    ABSTRACT: The role of the second-generation zotarolimus-eluting stent RESOLUTE in small-vessel coronary artery disease is unclear. The aim of this study was examine the angiographic results of RESOLUTE in de novo coronary lesions of ≥50 % diameter stenosis in target vessels ≤2.5 mm. From August 2008 to April 2010, 142 symptomatic patients with 159 lesions who fitted the inclusion criteria were treated with RESOLUTE. The mean age of patients was 66 ± 10 years, with male predominance (66 %). Diabetes mellitus was found in 62 (43.7 %) patients, whereas multivessel disease was observed in 105 (73.9 %). The mean stent size and length used were 2.33 ± 0.13 and 22 ± 8 mm, respectively. Follow-up angiography was performed on 143 (89.9 %) lesions in 127 (89.4 %) patients at a mean of 10.3 ± 3.6 months. Angiographic restenosis was found in 9 (6.3 %) lesions; the late loss was 0.26 ± 0.34 mm. At 1-year follow-up there were four cardiovascular deaths, two nonfatal myocardial infarctions, and six repeated revascularizations. The resultant major adverse cardiac event rate was 8.5 %. The use of RESOLUTE to treat small-vessel disease is associated with good clinical and angiographic outcomes at 1 year.
    Heart and Vessels 02/2013; · 2.05 Impact Factor
  • Article: Prolongation of PR interval is associated with endothelial dysfunction and activation of vascular repair in high-risk cardiovascular patients.
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    ABSTRACT: PURPOSE: Epidemiological studies showed that PR prolongation is associated with increased risk of adverse cardiovascular outcomes. We investigated the relations of PR interval with indices of vascular function and endothelial repair as the underlying mechanisms. METHODS: The study comprised 348 high-risk patients with prior coronary artery disease, ischemic stroke, and/or diabetes mellitus recruited from medical outpatient clinics and 150 healthy subjects without such a history. PR interval was considered prolonged if >200 ms, as determined from resting 12-lead electrocardiogram. Vascular function was assessed by brachial flow-meditated dilatation (FMD) using high-resolution ultrasound. Circulating CD133(+)/KDR(+) endothelial progenitor cell (EPC) levels were measured by flow cytometry. RESULTS: Among healthy subjects, PR interval was inversely associated with FMD (R = -0.20, P = 0.015), but not with the level of circulating CD133(+)/KDR(+) EPC (R = 0.05, P = 0.58). Among high-risk cardiovascular patients, PR prolongation >200 ms was more common compared with healthy subjects (45/348 (13 %) versus 4/150 (3 %), P < 0.001). PR interval was associated inversely with FMD (R = -0.14, P = 0.01) and positively with circulating CD133(+)/KDR(+) EPC level (R = +0.14, P = 0.009). Circulating CD133(+)/KDR(+) EPC level was significantly increased in patients with PR prolongation >200 ms (0.87 ± 0.37 versus 0.68 ± 0.42 (log, ×10(-3)/ml), P = 0.005). Adjusted for potential confounders, increased PR interval remained independently associated with increased CD133(+)/KDR(+) EPC by +0.002 (95 % confidence interval (CI) 0.000 to 0.004 (log, ×10(-3)/ml), P = 0.011) and depressed FMD (B = -0.014 %, 95 % CI -0.027 to -0.002, P = 0.026). CONCLUSIONS: PR prolongation is associated with endothelial dysfunction and evidence of endothelial repair activation in patients with high cardiovascular risk.
    Journal of Interventional Cardiac Electrophysiology 02/2013; · 1.17 Impact Factor
  • Article: Randomized controlled trial of vitamin D supplement on endothelial function in patients with type 2 diabetes.
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    ABSTRACT: BACKGROUND: Suboptimal vitamin D status is associated with endothelial dysfunction and an increased risk of cardiovascular diseases but it is unclear whether vitamin D supplementation is beneficial. The aim was to investigate the effect of vitamin D supplementation on endothelial function in patients with type 2 diabetes mellitus (DM). METHODS: In a double-blind, placebo-controlled trial, we randomized 100 type 2 DM patients to vitamin D supplement (5000 IU/day, n = 50) or placebo (controls, n = 50) for 12 weeks. Assessment of vascular function with brachial artery flow-mediated dilatation (FMD), circulating levels of endothelial progenitor cells (EPCs) and brachial-ankle pulse wave velocity, and metabolic parameter, high-sensitivity C-reactive protein (hsCRP) and oxidative stress markers were performed before and after the supplementation. RESULTS: After 12 weeks, vitamin D treated patients had significant increases in serum 25-hydroxyvitamin D [25(OH)D] concentration (treatment effect 34.7 ng/mL, 95% CI 26.4-42.9, P < 0.001) and serum ionized calcium (treatment effect 0.037 mmol/L, 95% CI 0.007-0.067, P = 0.018); decreased serum parathyroid hormone concentration (treatment effect -0.55 pmol/L, 95% CI -1.08 to -0.02, P = 0.042) compared to patients who received placebo. Nevertheless, vitamin D supplementation did not improve vascular function as determined by FMD, circulating EPC count or baPWV (all P > 0.05). Furthermore, hsCRP, oxidative stress markers, low- and high-density lipoprotein and glycated hemoglobin were also similar between two groups (all P > 0.05). CONCLUSION: In patients with type 2 DM, 12 weeks oral supplementation of vitamin D did not significantly affect vascular function or serum biomarkers of inflammation and oxidative stress. CLINICAL TRIAL NUMBER: HKCTR-867, www.hkclinicaltrials.com.
    Atherosclerosis 12/2012; · 3.79 Impact Factor
  • Article: Angiographic and Clinical Outcomes of Everolimus-Eluting Stent in the Treatment of Extra Long Stenoses (AEETES).
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    ABSTRACT: Objectives: The purpose of this study was to examine the angiographic and clinical results of stent full metal jacket in treating long lesions using everolimus-eluting stents (EES). Background: Data are lacking regarding the use of EES for this lesion subgroup. Methods: From 2007 to 2011, 77 symptomatic patients who had severe coronary stenoses necessitating implantation of stents with total length longer than 60 mm were treated with overlapping EES. Results: The mean age of patient was 61 ± 11 years with male predominance (66%). Diabetes mellitus was seen in 35 (45.5%) patients. Majority of patients had class III angina with normal heart function. On average, 3.1 stents were implanted per lesion; the mean stent size and length were 2.70 ± 0.28 mm and 82 ± 16 mm. Restudy angiography was performed on 71 patients (72 lesions) at 8.9 ± 2.5 months. Angiographic restenosis was seen in 9 (12.5%) lesions; the lesion length and late loss were 67 ± 15 mm and 0.4 ± 0.6 mm, respectively. The use of intravascular ultrasound has been found to be a predictor of less restenosis (P = 0.02; HR: 0.02; CI: 0.01-0.59). The in-hospital and 1 year major adverse cardiac event rates were 7.8% and 13%. The annual cardiac death rates were 2.6%, 3.4%, and 5.3% in the first 3 years. Conclusions: The use of EES full metal jacket for long lesions is only associated with good short-term clinical and angiographic outcomes. Long-term follow-up has revealed a high cardiac death rate which may necessitate prolongation of dual antiplatelet therapy. (J Interven Cardiol 2012;**:1-7).
    Journal of Interventional Cardiology 12/2012; · 1.18 Impact Factor
  • Article: Myocardial dysfunction in patients with type 2 diabetes mellitus: role of endothelial progenitor cells and oxidative stress.
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    ABSTRACT: BACKGROUND: Endothelial progenitor cells (EPCs) are responsible for angiogenesis and maintenance of microvascular integrity, the number of EPCs is correlated with oxidative stress. Their relation to myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM) is nonetheless unknown. METHODS: Eighty-seven patients with T2DM and no history of coronary artery disease were recruited. Transthoracic echocardiography and detailed evaluation of left ventricular (LV) systolic function by 2-dimensional (2D) speckle tracking derived strain analysis in 3 orthogonal directions was performed. Four subpopulations of EPCs, including CD34+, CD133+, CD34+/kinase insert domain-containing receptor (KDR) + and CD133+/KDR + EPCs, were measured by flow cytometry. Oxidative stress was assessed by superoxide dismutase (SOD). RESULTS: The mean age of the patients was 62 +/- 9 years and 39.6% were male. Those with an impaired longitudinal strain had a lower number of CD34+ EPCs (2.82 +/- 1.87% vs. 3.74 +/- 2.12%, P < 0.05) than those with preserved longitudinal strain. When compared with those with preserved circumferential strain, patients with an impaired circumferential strain had a lower number of CD34+ EPCs (2.63 +/- 1.80% vs. 3.87 +/- 2.10%, P < 0.01) and SOD level (0.13 +/- 0.06U/ml vs. 0.20 +/- 0.08U/ml, P < 0.01). Patients with an impaired radial strain nonetheless had a lower number of CD34+ EPCs (2.62 +/- 2.08% vs. 3.69 +/- 1.99%, P < 0.05). Multivariate analysis demonstrated that only impaired global circumferential strain remained significantly associated with CD34 + EPCs and SOD. CONCLUSIONS: LV global circumferential strain was independently associated with number of CD34+ EPCs and SOD. These findings suggest that myocardial dysfunction in patients with T2DM is related to depletion of EPCs and increased oxidative stress.
    Cardiovascular Diabetology 12/2012; 11(1):147. · 3.35 Impact Factor
  • Article: Prognostic implications of surrogate markers of atherosclerosis in low to intermediate risk patients with Type 2 Diabetes.
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    ABSTRACT: Type 2 diabetes mellitus (T2DM) patients are at increased risk of developing cardiovascular events. Unfortunately traditional risk assessment scores, including the Framingham Risk Score (FRS), have only modest accuracy in cardiovascular risk prediction in these patients. We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10 years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61 ± 16 months. A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0 ± 4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59 ± 0.07 (P = 0.21). Among different vascular assessments, CACS > 40 had the best prognostic value (AUC 0.81 ± 0.06, P < 0.01) and offered significantly better accuracy in prediction compared with FRS (P = 0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS > 40 as an independent predictor of atherosclerotic events in T2DM patients (Hazards Ratio 27.11, 95% Confidence Interval 3.36-218.81, P = 0.002). In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS > 40 was an independent predictor for atherosclerotic events.
    Cardiovascular Diabetology 08/2012; 11:101. · 3.35 Impact Factor
  • Article: Association of lower habitual physical activity level with mitochondrial and endothelial dysfunction in patients with stable coronary artery disease.
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    ABSTRACT: Background: Exercise training improves endothelial function in patients with coronary artery disease (CAD) through unclear mechanisms. We hypothesized that mitochondrial dysfunction related to a lower habitual physical activity level (PAL) is associated with endothelial dysfunction. Methods and Results: We assessed habitual PAL by a validated International Physical Activity Questionnaire, brachial flow-mediated dilation (FMD) and serum lactate, pyruvate, fasting glucose and lipid profiles in 105 CAD patients (age 68±10; 87% men). As defined by the lactate/pyruvate ratio (LP ratio) ≥75(th) percentile of the age-and sex-matched controls (ie, ≥18), mitochondrial dysfunction was observed in 33/105 (31%) patients. With decreasing PAL tertiles, there were significant linear trends of lower FMD (P=0.004) and higher LP ratio (P=0.009). Multivariate logistic regression found that the lowest compared with the highest PAL tertile (adjusted odds ratio=3.78, P=0.02) had more patients with high LP ratio. After adjustment for cardiovascular risk factors and medications, the lowest compared to the highest PAL tertile had significantly lower FMD (absolute decrease 1.25%, P=0.03); and high LP ratio was associated with impaired FMD (absolute reduction 1.09%, P=0.03). Conclusions: In CAD patients, a lower level of habitual PAL is associated with impaired FMD and increased prevalence of mitochondrial dysfunction as defined by high LP ratio. Moreover, high LP ratio predicts a lower FMD, suggesting that the occurrence of mitochondrial dysfunction with lower habitual PAL is associated with endothelial dysfunction in CAD patients.  (Circ J 2012; 76: 2572-2578).
    Circulation Journal 07/2012; 76(11):2572-8. · 3.77 Impact Factor
  • Article: Jeopardised Inferior Myocardium (JIM) score: an arithmetic electrocardiographic score to predict the infarct-related artery in inferior myocardial infarction.
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    ABSTRACT: A few electrocardiographic criteria have been described to identify the infarct-related artery in inferior myocardial infarction. The aim of this study was to devise an arithmetic score to further improve the diagnostic accuracy. From 2004 to 2006, 78 patients who underwent primary angioplasty for inferior myocardial infarction within 6 hours from symptom onset were recruited for electrocardiographic and angiographic analysis. The mean age of patients was 65 ± 12 years with male predominance (74%). Less ST depression in lead I and aVL, and more prominent ST depression in lead V1-3 were observed in left circumflex artery (LCX) than right coronary artery (RCA) occlusions. In addition, more prominent ST depression in lead I and ST elevation in V1 were found in proximal RCA than distal RCA occlusions. Based on the findings, the Jeopardised Inferior Myocardium (JIM) score was constructed and defi ned as [II-V3/III+V1- I]. The sensitivity and specificity of JIM score ≤0.5 to predict proximal RCA occlusions; 0.5 <JIM score ≤1.5 to predict distal RCA occlusions; and JIM score >1.5 to predict LCX occlusions were 58% and 85%, 69% and 68%, and 79% and 94%, respectively. The accuracy of prediction is slightly better than the 2 previously reported criteria. By taking into account more leads, the JIM score is capable of identifying the infarct-related artery with an improved diagnostic accuracy.
    Annals of the Academy of Medicine, Singapore 07/2012; 41(7):300-4. · 1.25 Impact Factor
  • Article: Prognostic role of coronary calcification in patients with rheumatoid arthritis and systemic lupus erythematosus.
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    ABSTRACT: To study the predictive value of coronary calcification score (CCS) for future cardiovascular (CVS) events as detected by multi-detector computed tomography (MDCT) in patients with rheumatoid arthritis(RA) and systemic lupus erythematosus (SLE). A total of 152 patients with RA and SLE, and 106 healthy controls underwent MDCT to measure CCS. All patients were prospectively followed up for major CVS events. Compared with controls, patients with RA and SLE had a significantly higher mean CCS (42.2±154.3 vs. 1.4±13.0, p<0.01) and prevalence of CCS 1-10, CCS 11-100 and CCS>100 (all p<0.05). After a mean period of 4.3±0.6 years, major CVS events occurred in 10 patients with RA and SLE. In patients with RA and SLE, a higher major CVS events rate occurred in patients with CCS 1-10 (5.0%), CCS 11-100 (14.3%) and CCS >100 (40.0%) than those with CCS=0 (1.0%, p<0.01). Multivariate Cox regression analysis revealed that hypercholesterolemia (hazard ratio (HR) 11.2, confidence interval (CI 1.4-89.3, p=0.02) and CCS>100 (HR 11.1, CI 1.31-95.0, p=0.03) were independent predictors of combined events. Coronary calcification detected by MDCT independently predicts CVS events in patients with RA and SLE. Risk stratification by assessment of CCS may have an important role in patients with systemic inflammatory disease.
    Clinical and experimental rheumatology 02/2012; 30(3):345-50. · 2.15 Impact Factor
  • Article: Left ventricular mechanical dyssynchrony impairs exercise capacity in patients with coronary artery disease with preserved left ventricular systolic function and a QRS duration ≤ 120 ms.
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    ABSTRACT: Left ventricular (LV) mechanical dyssynchrony can lead to impairment of LV function and is associated with adverse clinical outcomes in coronary artery disease (CAD) patients. The impact of LV dyssynchrony on exercise capacity (EC) in patients with CAD was investigated. An echocardiographic examination with tissue Doppler imaging and exercise treadmill testing in 151 CAD patients with normal LV ejection fraction was performed. LV intra- and inter-ventricular dyssynchrony were defined by the standard deviation of time interval between LV 6 basal segments (Ts-SD), and the time interval from the right ventricular (RV) free wall to LV lateral wall (Ts-RV) respectively, and EC was measured as metabolic equivalents (METs) on the treadmill. Patients with impaired EC (defined by a METs ≤ 8, which is the mean MET of the study population) were older (71 ± 7 vs. 62 ± 2 years, P<0.01), however, there were no differences in gender and clinical status such as prevalence of prior myocardial infarction (MI), regional wall motion abnormality (RWMA), and coronary revascularization between patients with (n=90) or without (n=61) impaired EC. Univariate analysis showed that age, body mass index, LV systolic and diastolic volume, mitral inflow A velocity, and Ts-SD were all significantly associated with METs (all P<0.05). However, multivariate regression analysis revealed that old age (odd ratio [OR]: 1.136, 95% confidence interval [CI]: 1.080-1.196, P<0.001), and Ts-SD (OR: 1.026, 95%CI: 1.003-1.049, P=0.027) only were independent predictors for impaired EC. In patients with CAD, LV systolic dyssynchrony predicts impaired EC independently of history of previous MI or RWMA.
    Circulation Journal 02/2012; 76(3):682-8. · 3.77 Impact Factor
  • Article: Subclinical left ventricular dysfunction revealed by circumferential 2D strain imaging in patients with coronary artery disease and fragmented QRS complex.
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    ABSTRACT: Fragmented QRS (fQRS) complexes on a routine 12-lead electrocardiogram were associated with adverse cardiac events, including sudden death in patients with coronary artery disease (CAD). To investigate the relationship between the fQRS complex and global and regional left ventricular (LV) functions in patients with CAD. The study consisted of 176 patients (68 ± 9 years; 145 [82%] men) with CAD with narrow QRS duration and preserved LV ejection fraction (>45%). All patients underwent detailed 2-dimensional speckle-tracking echocardiography to determine global and segmental (basal, middle, and apical) LV strains and strain rates and were prospectively followed-up in the outpatient clinic. Fifty-five patients (31%) had fQRS complexes. Global, middle, and apical LV longitudinal, radial, and circumferential strains and strain rates were significantly lower in the fQRS group than in the non-fQRS group (all P <.05). Multivariate logistic regression analysis revealed that the fQRS complex was associated with decreased global circumferential strain (odds ratio 1.19; 95% confidence interval 1.06-1.33; P = .003) and multivessel disease (odds ratio 3.69; 95% confidence interval 1.35-10.08; P = .011). Kaplan-Meier analysis revealed that event-free survival for cardiac events was significantly lower in the fQRS group than in the non-fQRS group (P = .036). Our results demonstrated that the fQRS complex in patients with CAD with preserved LV ejection fraction was associated with subclinical global and regional LV dysfunctions as detected by 2-dimensional speckle-tracking imaging, and the results also predicted adverse cardiac events.
    Heart rhythm: the official journal of the Heart Rhythm Society 01/2012; 9(6):928-35. · 4.56 Impact Factor
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    Article: Myocardial structural alteration and systolic dysfunction in preclinical hypertrophic cardiomyopathy mutation carriers.
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    ABSTRACT: To evaluate the presence of myocardial structural alterations and subtle myocardial dysfunction during familial screening in asymptomatic mutation carriers without hypertrophic cardiomyopathy (HCM) phenotype. Sixteen HCM families with pathogenic mutation were studied and 46 patients with phenotype expression (Mut+/Phen+) and 47 patients without phenotype expression (Mut+/Phen-) were observed. Twenty-five control subjects, matched with the Mut+/Phen- group, were recruited for comparison. Echocardiography was performed to evaluate conventional parameters, myocardial structural alteration by calibrated integrated backscatter (cIBS) and global and segmental longitudinal strain by speckle tracking analysis. All 3 groups had similar left ventricular dimensions and ejection fraction. Basal anteroseptal cIBS was the highest in Mut+/Phen+ patients (-14.0±4.6 dB, p<0.01) and was higher in Mut+/Phen- patients as compared to controls (-17.0±2.3 vs. -22.6±2.9 dB, p<0.01) suggesting significant myocardial structural alterations. Global and basal anteroseptal longitudinal strains (-8.4±4.0%, p<0.01) were the most impaired in Mut+/Phen+ patients as compared to the other 2 groups. Although global longitudinal strain was similar between Mut+/Phen- group and controls, basal anteroseptal strain was lower in Mut+/Phen- patients (-14.1±3.8%, p<0.01) as compared to controls (-19.9±2.9%, p<0.01), suggesting a subclinical segmental systolic dysfunction. A combination of >-19.0 dB basal anteroseptal cIBS or >-18.0% basal anteroseptal longitudinal strain had a sensitivity of 98% and a specificity of 72% in differentiating Mut+/Phen- group from controls. The use of cIBS and segmental longitudinal strain can differentiate HCM Mut+/Phen- patients from controls with important clinical implications for the family screening and follow-up of these patients.
    PLoS ONE 01/2012; 7(5):e36115. · 4.09 Impact Factor
  • Article: Increased myocardial fibrosis and left ventricular dysfunction in Cushing's syndrome.
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    ABSTRACT: Active Cushing's syndrome (CS) is associated with cardiomyopathy, characterized by myocardial structural, and ultrastructural abnormalities. The extent of myocardial fibrosis in patients with CS has not been previously evaluated. Therefore, the objective of this study was to assess myocardial fibrosis in CS patients, its relationship with left ventricular (LV) hypertrophy and function, and its reversibility after surgical treatment. Fifteen consecutive CS patients (41±12 years) were studied together with 30 hypertensive (HT) patients (matched for LV hypertrophy) and 30 healthy subjects. Echocardiography was performed in all patients including i) LV systolic function assessment by conventional measures and by speckle tracking-derived global longitudinal strain, ii) LV diastolic function assessment using E/E', and iii) myocardial fibrosis assessment using calibrated integrated backscatter (IBS). Echocardiography was repeated after normalization of cortisol secretion (14±3 months). CS patients showed the highest value of calibrated IBS (-15.1±2.5  dB) compared with HT patients (-20.0±2.6  dB, P<0.01) and controls (-23.8±2.4  dB, P<0.01), indicating increased myocardial fibrosis independent of LV hypertrophy. Moreover, calibrated IBS in CS patients was significantly related to both diastolic function (E/E', r=0.79, P<0.01) and systolic function (global longitudinal strain, r=0.60, P=0.02). After successful surgical treatment, calibrated IBS normalized (-21.0±3.8 vs -15.1±2.5  dB, P<0.01), suggestive of regression of myocardial fibrosis. Patients with CS have increased myocardial fibrosis, which is related to LV systolic and diastolic dysfunction. Successful treatment of CS normalizes the extent of myocardial fibrosis. Therefore, myocardial fibrosis appears to be an important factor in the development and potential regression of CS cardiomyopathy.
    European Journal of Endocrinology 01/2012; 166(1):27-34. · 3.42 Impact Factor
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    Article: Impact of glycemic control on circulating endothelial progenitor cells and arterial stiffness in patients with type 2 diabetes mellitus.
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    ABSTRACT: Patients 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. We 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. Patients 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). In 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.
    Cardiovascular Diabetology 12/2011; 10:113. · 3.35 Impact Factor
  • Article: Left ventricular dysfunction assessed by speckle-tracking strain analysis in patients with systemic sclerosis: relationship to functional capacity and ventricular arrhythmias.
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    ABSTRACT: Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular inflammation and fibrosis. Visceral involvement, including cardiac manifestations, can lead to severe clinical complications, such as congestive heart failure, arrhythmias, and sudden death. Conventional echocardiography parameters have limited sensitivity to detect subtle myocardial dysfunction in patients with SSc. The aim of this study was to assess, using novel speckle-tracking strain analysis, the presence of myocardial dysfunction in patients with SSc, and to investigate its relationship to functional capacity and ventricular arrhythmias. A total of 104 patients with SSc (mean ± SD age 54 ± 12 years, 77% female) were included and underwent cardiopulmonary exercise testing, 24-hour electrocardiography (EKG) Holter monitoring, and transthoracic echocardiography. For comparison, 37 matched healthy control subjects were included. The total patient population consisted of 51 patients with limited cutaneous SSc and 53 with diffuse cutaneous SSc. Peak VO(2) was a mean ± SD 91 ± 20% predicted, and 28 patients had abnormal findings (ventricular tachycardia or ventricular ectopics >100/day) on EKG Holter monitoring. Patients with SSc, as compared with controls, had impaired global longitudinal and circumferential strains (mean ± SD -18.2 ± 1.8% versus -21.3 ± 1.7% and -18.2 ± 2.3% versus -21.3 ± 2.1%, respectively; each P < 0.01), but there was no difference in the left ventricular ejection fraction between patients and controls (mean ± SD 63.5 ± 7.2% versus 64.6 ± 4.4%; P = 0.20). In patients with SSc, global longitudinal and circumferential strains each correlated with the peak VO(2) (r = -0.46 and r = -0.41, respectively; both P < 0.01), and multivariate analysis confirmed the independent association of each strain measure with the peak VO(2). Compared to SSc patients with normal results on EKG Holter monitoring, SSc patients with abnormal results showed impaired global longitudinal strains (-18.5 ± 1.5% versus -17.1 ± 2.1%; P < 0.01) and circumferential strains (-18.7 ± 2.0% versus -17.3 ± 2.5%; P = 0.01), and each strain measure was independently associated with abnormal Holter findings. Speckle-tracking strain analysis can detect subtle myocardial dysfunction in patients with SSc. Importantly, decreased global longitudinal and circumferential strains are associated with lower functional capacity and rhythm disturbances in patients with SSc.
    Arthritis & Rheumatism 12/2011; 63(12):3969-78. · 7.87 Impact Factor
  • Article: Abnormal vascular function in PR-interval prolongation.
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    ABSTRACT: Underlying mechanisms of PR-interval prolongation leading to increased risk of adverse cardiovascular outcomes, including atrial fibrillation, are unclear. This study aims to investigate the relation between PR interval and changes in vascular function. We hypothesize that there exists an intermediate pathological stage between electrocardiographic PR prolongation and adverse cardiovascular outcomes, which could be reflected by changes in surrogate measurements of vascular function. We recruited 88 healthy subjects (mean age 57.5 ± 9.8 y, 46% male) from a community-based health screening program who had no history of cardiovascular disease or diabetes mellitus. PR interval was determined from a resting 12-lead electrocardiogram. Vascular function was noninvasively assessed by flow-mediated dilation (FMD) using high-resolution ultrasound and brachial-ankle pulse wave velocity (PWV) using a vascular profiling system. Only 3 subjects had a PR-interval length longer than the conventional cutoff of 200 ms. The PR-interval length was associated inversely with FMD (Pearson r = -0.30, P = 0.004) and positively with PWV (r = 0.40, P < 0.001). Adjusting for potential confounders, increased PR-interval length by each 25 ms was independently associated with reduced FMD by -1 unit (absolute %, B = -0.04 [95% confidence interval: -0.080 to -0.002, P = 0.040)] and increased PWV by +103 cm/second (B = +4.1 [95% confidence interval: 0.6-7.6, P = 0.023]). This study shows that PR-interval length, even in the conventionally normal range, is independently associated with endothelial dysfunction and increased arterial stiffness in healthy subjects free of atherosclerotic disease. This suggests the presence of a systemic, intermediate pathologic stage of the vasculature in PR prolongation before clinically manifest cardiovascular events, and could represent a mediating mechanism.
    Clinical Cardiology 10/2011; 34(10):628-32. · 2.15 Impact Factor
  • Article: Distribution of culprit lesions in patients with ST-segment elevation acute myocardial infarction treated with primary percutaneous coronary intervention.
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    ABSTRACT: Data regarding the distribution of vulnerable lesions in the coronary arteries are scarce. The aim was to evaluate the frequency and distribution of culprit lesions in patients with ST-segment elevation acute myocardial infarction. In addition, the location of culprit lesions was related to infarct size. Consecutive patients (N=1533, mean age 61±12 years) were evaluated. All patients were treated with primary percutaneous coronary intervention and underwent two-dimensional echocardiography less than 48 h after admission. The majority of the culprit lesions were located in the left anterior descending coronary artery (LAD, 45%), followed by the right coronary artery (RCA, 38%), and left circumflex coronary artery (LCX, 14%). Subanalysis demonstrated that patients with a culprit lesion in the LAD and LCX had significantly higher-peak cardiac enzymes compared with patients with culprit lesions in the RCA. In addition, patients with proximal LAD and LCX lesions had significantly worse left ventricular function compared with patients with mid or distal lesions. Plaque rupture resulting in acute myocardial infarction is more likely to occur in the proximal parts of the LAD and RCA. In addition, the location of culprit lesions was related to infarct size. Therefore, knowledge of the distribution of vulnerable lesions is important for identifying patients at risk for acute coronary events.
    Coronary artery disease 09/2011; 22(8):533-6. · 1.56 Impact Factor
  • Article: Ethnic differences in cardiovascular risk in rheumatic disease: focus on Asians.
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    ABSTRACT: Rheumatic diseases are associated with high cardiovascular morbidity and mortality. Considerable differences exist in the frequency of cardiovascular disease (CVD) risk factors and events among people of different ethnic origins, but little is known of the ethnic variations in the relative distribution of CVD risk factors and the degree of atherosclerosis in patients with rheumatic diseases. Understanding this variation will provide insight into the underlying pathogenesis of CVD in patients with rheumatic diseases, and aid in future studies of the detection and management of this complication. In general, although Asian patients seem to have fewer background CVD risk factors and are less affected by metabolic syndrome (MetS) than their non-Asian counterparts, those with rheumatic disease are equally as susceptible to CVD. Furthermore, it seems that systemic inflammation and mechanisms that do not involve conventional CVD risk factors and MetS have an important role in the development of atherosclerosis in patients with rheumatic diseases. Here we examine the frequency of conventional CVD risk factors and the prevalence of MetS in both Asian and non-Asian patients with selected rheumatic diseases. We also discuss the burden of CVD, as evaluated using various surrogate markers in these patients, and their overall CVD mortality rate.
    Nature Reviews Rheumatology 09/2011; 7(10):609-18. · 8.39 Impact Factor
  • Article: Age- and gender-specific differences in the prognostic value of CT coronary angiography.
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    ABSTRACT: To evaluate the potential age- and gender-specific differences in the incidence and prognostic value of coronary artery disease (CAD) in patients undergoing CT coronary angiography (CTA). In this multicentre prospective registry study, 2432 patients (mean age 57 ± 12, 56% male) underwent CTA for suspected CAD. Patients were stratified into four groups according to age <60 or ≥60 years and, male or female gender. A composite end point of cardiac death and non-fatal myocardial infarction. CTA results were normal in 991 (41%) patients, showed non-significant CAD in 761 (31%) patients and significant CAD in the remaining 680 (28%) patients. During follow-up (median 819 days, 25-75th centile 482-1142) a cardiovascular event occurred in 59 (2.4%) patients. The annualised event rate was 1.1% in the total population (men=1.3% and women=0.9%). In patients aged <60 years, the annualised event rate of male and female patients was 0.6% and 0.5%, respectively. Among patients aged ≥60 years the annualised event rate was 1.9% in male and 1.1% in female patients. Observations on CTA predicted events in male patients, both age <60 and ≥60 years and in female patients age ≥60 years (log-rank test in all groups, p<0.01). However, CTA provided limited prognostic value in female patients aged <60 years (log-rank test, p=0.45). After age and gender stratification, CTA findings were shown to be of limited predictive value in female patients aged <60 years as compared with male patients at any age and female patients aged ≥60 years.
    Heart (British Cardiac Society) 09/2011; 98(3):232-7. · 4.22 Impact Factor