Leong Loke Ng - Academia.edu (original) (raw)

Papers by Leong Loke Ng

$Research paper thumbnail of Higher doses of loop diuretics limit uptitration of angiotensin-converting enzyme inhibitors in patients with heart failure and reduced ejection fraction$

Clinical Research in Cardiology, 2020

Background Loop diuretics are frequently prescribed to patients with heart failure and reduced ej... more Background Loop diuretics are frequently prescribed to patients with heart failure and reduced ejection fraction (HFrEF) for the treatment of congestion; however, they might hamper uptitration of inhibitors of the renin–angiotensin system. Methods Loop diuretic dose at baseline was recorded in 2338 patients with HFrEF enrolled in BIOSTAT-CHF, an international study of HF patients on loop diuretic therapy who were eligible for uptitration of angiotensin-converting enzyme inhibitors (ACEi)/mineralocorticoid receptor antagonists (MRA). The association between loop diuretic dose and uptitration of ACEi/MRA to percentage of target dose was adjusted for a previously published model for likelihood of uptitration and a propensity score. Results Baseline median loop diuretic dose was 40 [40–100] mg of furosemide or equivalent. Higher doses of loop diuretics were associated with higher NYHA class and higher levels of NT-proBNP, more severe signs and symptoms of congestion, more frequent MRA u...

$Research paper thumbnail of 348Association of arterial stiffness with left ventricular remodelling in heart failure with preserved ejection fraction$

European Heart Journal - Cardiovascular Imaging, 2019

Clinical Science, 1988

1. Leucocyte Na+ influx in media containing 10 mmol/l Na+ was studied directly using a triple-iso... more 1. Leucocyte Na+ influx in media containing 10 mmol/l Na+ was studied directly using a triple-isotope method for measuring initial 22Na uptake rates in 20 normal and 18 untreated hypertensive subjects. The effects of 1 mmol/l amiloride (a Na+-H+-antiport inhibitor) and 0.1 mmol/l bumetanide (a Na+, K+, Cl−-symport inhibitor) were also examined. 2. The total, amiloride-sensitive and bumetanide-sensitive influx rates were raised in hypertensive compared with normotensive subjects [median (range): total 0.63 (0.25–1.82) vs 0.40 (0.09–0.65) mmol min−1 l−1, P < 0.002; amiloride-sensitive 0.43 (0.18–1.56) vs 0.26 (0.04–0.48) mmol min−1 l−1, P < 0.002; bumetanide-sensitive 0.12 (−0.03 to 0.83) vs 0.02 (−0.25 to 0.21) mmol min−1 l−1, P < 0.005]. 3. We conclude that hypertensive patients have a raised leucocyte total Na+ influx when measured in media containing 10 mmol/l Na+ and that this is contributed mainly by amiloride-sensitive and bumetanide-sensitive Na+ influx mechanisms.

Europace, 2014

Sudden cardiac death (SCD) risk prediction has substantial limitations. The Regional Restitution ... more Sudden cardiac death (SCD) risk prediction has substantial limitations. The Regional Restitution Instability Index (R2I2) is a promising new ECG-based biomarker of SCD. R2I2 uses the surface 12-lead ECG to quantify regional heterogeneity of electrical restitution, a property of ventricular myocardium implicated in arrhythmogenesis. We investigated the potential of a combined R2I2 and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) SCD risk marker in an ischaemic cardiomyopathy cohort.

Purpose: The Regional Restitution Instability Index (R2I2) is a promising new ECG based biomarker... more Purpose: The Regional Restitution Instability Index (R2I2) is a promising new ECG based biomarker of sudden cardiac death (SCD). This abstract explores the potential of a combined R2I2 and NT-pro-BNP SCD risk marker in an ischaemic cardiomyopathy cohort. Methods: Blinded prospective observational study. Study group: 55 ischaemic cardiomyopathy patients undergoing risk stratification for implantable cardioverter defibrillator (ICD). The R2I2 technique has been described previously: an EP study is performed and ECG surrogates for action potential duration and diastolic interval are used to measure restitution heterogeneity. Plasma samples obtained on the day of the ICD procedure were assayed for NT-pro-BNP. Results: During median follow up of 22 months, 15 patients experienced ventricular arrhythmia (VA)/SCD. R2I2 was significantly higher in patients experiencing VA/SCD than those not (mean±SEM: 1.12±0.05 vs 0.84±0.09, p=0.004). R2I2 was independent of log NT-pro-BNP and left ventricu...

In vivo (Athens, Greece)

The ability to predict mode, as well as risk, of death in left ventricular systolic dysfunction (... more The ability to predict mode, as well as risk, of death in left ventricular systolic dysfunction (LVSD) is important, as the clinical and cost-effectiveness of implantable cardioverter defibrillators (ICD) therapy depends on its use in appropriately selected patient populations. The value of a proteomic approach in identifying prognostic biomarkers in LVSD is unknown. The aims of this pilot study were to use proteomic techniques to identify serum biomarkers associated with LVSD and to prospectively explore their association with prognosis. Serum was analysed by surface-enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) in patients with (n=78) and without (n=45) systolic heart failure (SHF). Spectra were compared to identify differentially expressed signal peaks as potential biomarker indicators. The ability of these peaks to predict all-cause mortality and survival with appropriate ICD therapy was then tested prospectively in patients with ICDs, on t...

Journal of Cystic Fibrosis, 2007

British Journal of Nutrition, 1989

Cellular sodium transport via the Na+, K+-ATPase contributes significantly to daily energy expend... more Cellular sodium transport via the Na+, K+-ATPase contributes significantly to daily energy expenditure. The effect of a meal on leucocyte Na+ transport and intracellular electrolytes was therefore investigated in lean normal subjects at room temperatures of 23° and 33°, to determine if the Na pump responds to the need for thermogenesis. In the fasting state, the ouabain-sensitive efflux rate which reflects active Na+ transport, and the intracellular electrolytes were similar. At 2 h after eating a 4·2 MJ (1000 kcal) meal, the ouabain-sensitive efflux rate constant rose when the room temperature was 23° but not at 33°. The ouabain-sensitive Na+ efflux rate, an index of active Na+ transport, 0rose post-prandially at 23° only. The post-prandial activation of leucocyte active Na efflux in normal subjects was blunted at higher environmental temperatures, when the need for thermogenesis was reduced.

Journal of Clinical Medicine

Gestational Diabetes Mellitus (GDM) is the most common metabolic complication during pregnancy an... more Gestational Diabetes Mellitus (GDM) is the most common metabolic complication during pregnancy and is associated with serious maternal and fetal complications such as pre-eclampsia and stillbirth. Further, women with GDM have approximately 10 times higher risk of diabetes later in life. Children born to mothers with GDM also face a higher risk of childhood obesity and diabetes later in life. Early prediction/diagnosis of GDM leads to early interventions such as diet and lifestyle, which could mitigate the maternal and fetal complications associated with GDM. However, no biomarkers identified to date have been proven to be effective in the prediction/diagnosis of GDM. Proteomic approaches based on mass spectrometry have been applied in various fields of biomedical research to identify novel biomarkers. Although a number of proteomic studies in GDM now exist, a lack of a comprehensive and up-to-date meta-analysis makes it difficult for researchers to interpret the data in the existing...

European Journal of Heart Failure, 2010

Aims Diuretics, when used to treat congestion in patients with chronic heart failure, improve sym... more Aims Diuretics, when used to treat congestion in patients with chronic heart failure, improve symptoms and, perhaps, prognosis but little information is available to guide their use in patients with left ventricular systolic dysfunction (LVSD) who are not congested. Chronic diuretic therapy causes persistent and potentially harmful neuroendocrine activation. Alternatively, in patients in whom neuroendocrine activation is blocked with angiotensin-converting enzyme (ACE)-inhibitors and b-blockers, diuretics may be beneficial by decreasing preload and afterload and preventing congestion. We aimed to assess the effect of the loop diuretic, torasemide on quality of life, and surrogate markers of prognosis when given to patients with LVSD who were not clinically congested and who were optimally treated with ACE-inhibitors (or angiotensin receptor antagonists) and b-blockers. Methods and results Thirty patients with stable LVSD who had no clinically detectable fluid overload were randomized to receive either torasemide 5 mg daily or placebo for 3 months (Phase A), and after a washout phase of 2 months, cross-over was performed for 3 months (Phase B). Diuretic therapy did not cause significant change in peak VO 2 , mean N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) levels, or measures of quality of life compared with placebo. Diuretic therapy did however lead to significant fall in systolic and diastolic blood pressures and increase in plasma renin levels compared with placebo. Conclusion Diuretic therapy with torasemide is not superior to placebo in improving peak VO 2 or reducing NT-proBNP levels in patients with left ventricular dysfunction who are not clinically congested.

Clinical Chemistry, Apr 30, 2017

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Information about reprints can be found online at: Reprints: document. Permissions and Rights Que... more Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer information about this process is available in the requested is located, click Request Permissions in the middle column of the Web page under Services. Further Center, not the Editorial Office. Once the online version of the published article for which permission is being can be obtained via RightsLink, a service of the Copyright ClearanceCirculation: Cardiovascular Geneticsin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on March 6,

Journal of the American College of Cardiology, Jan 3, 2017

Proenkephalin A (PENK) and its receptors are widely distributed. Enkephalins are cardiodepressive... more Proenkephalin A (PENK) and its receptors are widely distributed. Enkephalins are cardiodepressive and difficult to measure directly. PENK is a stable surrogate analyte of labile enkephalins that is correlated inversely with renal function. Cardiorenal syndrome is common in acute heart failure (HF) and portends poor prognosis. This study assessed the prognostic value of PENK in acute HF, by identifying levels that may be useful in clinical decisions, and evaluated its utility for predicting cardiorenal syndrome. This multicenter study measured PENK in 1,908 patients with acute HF (1,186 male; mean age 75.66 ± 11.74 years). The primary endpoint was 1-year all-cause mortality; secondary endpoints were in-hospital mortality, all-cause mortality or HF rehospitalization within 1 year, and in-hospital worsening renal function, defined as a rise in plasma creatinine ≥26.5 μmol/l or 50% higher than the admission value within 5 days of presentation. During 1-year follow-up, 518 patients died....

Heart, 2015

association between plasma cortisol and CHD. The inconsistent results from observational studies ... more association between plasma cortisol and CHD. The inconsistent results from observational studies may be explained by: the inverse association between cortisol and obesity, which confounded the positive association of cortisol with other cardiovascular risk factors; and the use of single 'snapshot' plasma cortisol measurement rather than cumulative measure of cortisol exposure provided by genetic prediction. A bidirectional Mendelian randomisation analysis between plasma cortisol and BMI may yield greater clarity. To improve the strength of our genetic instrument an expanded CORNET GWAMA is currently underway. Measurements of cortisol may add value to predictions of CHD risk.

$Research paper thumbnail of Fibroblast‐growth‐factor‐23 in heart failure with preserved ejection fraction: relation to exercise capacity and outcomes$

ESC Heart Failure, 2020

Aims This study aimed to assess plasma fibroblast growth factor 23 (FGF23) in patients with heart... more Aims This study aimed to assess plasma fibroblast growth factor 23 (FGF23) in patients with heart failure with preserved ejection fraction (HFpEF) and its relation to inflammation, renal function, clinical and imaging characteristics, exercise capacity, and prognosis. Methods and results We performed a prospective, observational study of 172 age-matched and sex-matched subjects (HFpEF n = 130; controls n = 42, age 73 ± 9, female 50%) who underwent plasma biomarker sampling, echocardiography, cardiac magnetic resonance imaging, and 6 min walk testing (6MWT). The primary endpoint was the composite of all-cause death or HF hospitalization. FGF23 was higher in HFpEF compared with controls (62 [42-105] vs. 34 [22-41] pg/mL, P < 0.0001).

European Journal of Heart Failure, 2020

Natriuretic peptides [NP, including B-type natriuretic peptide (BNP) and amino-terminal prohormon... more Natriuretic peptides [NP, including B-type natriuretic peptide (BNP) and amino-terminal prohormone of BNP (NT-proBNP)] are the gold-standard biomarkers in heart failure (HF) management,1 with NP levels at presentation/admission routinely used for diagnostic and prognostic purposes.2 NP levels at discharge/follow-up also show association with outcomes,3 and NP levels following HF treatment add further value to tailoring risk.4 However, the usefulness of NP serial measurements beyond conventional HF treatment in clinical practice still remains a matter of controversy.3,5 A cohort with current HF guideline-based treatment would provide an ideal setting to revisit usefulness of NP serial measurements in risk stratification of HF patients, including the role of recently identified BNP molecular forms.6 The European multi-national BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) provides an opportunity for the aforementioned analysis, being a European cohort in w...