Publications by authors named "Kian Keong Poh"

166 Publications

Low Relative Valve Load is Associated With Paradoxical Low-Flow Aortic Stenosis Despite Preserved Left Ventricular Ejection Fraction and Adverse Clinical Outcomes.

Heart Lung Circ 2021 Jun 8. Epub 2021 Jun 8.

Department of Cardiology, National University Heart Centre Singapore, National University Health System, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Background: Paradoxical low-flow (LF) severe aortic stenosis (AS) despite preserved left ventricular (LV) ejection fraction (LVEF) has been shown to be distinct from normal-flow (NF) AS, with a poorer prognosis. Relative valve load (RVL) is a novel echocardiographic haemodynamic index based on the ratio of transaortic mean pressure gradient to the global valvulo-arterial impedance (Zva) in order to estimate the contribution of the valvular afterload to the global LV load. We aimed to determine the usefulness of RVL in LF AS versus NF AS.

Method: A total of 450 consecutive patients with medically managed severe AS (aortic valve area <1.0 cm) with preserved LVEF (>50%) were studied. Patients were divided into LF (stroke volume index <35 mL/m) or NF, and high RVL or low RVL. Baseline clinical and echocardiographic profiles, as well as clinical outcomes, were compared.

Results: There were 149 (33.1%) patients with LF. Despite higher global impedance in LF (Zva 6.3±2.4 vs 3.9±0.9 mmHg/mL/m; p<0.001) compared with NF, the RVL in LF AS was significantly lower (5.4±2.7 vs 9.8±5.1 mL/m; p<0.001). On multivariable analysis, low RVL (≤7.51) remained independently associated with poor clinical outcomes on Cox regression (hazard ratio, 1.31; 95% confidence interval, 1.03-1.68), with 53.2% sensitivity and 70.3% specificity. This was comparable to other prognostic indices in AS. Kaplan-Meier curves demonstrated that low RVL was associated with increased mortality.

Conclusions: Increased systemic arterial afterload may be important in the pathophysiology of LF AS. Low RVL was an independent predictor of poor clinical outcomes in medically managed severe AS. There may be a greater role in the attenuation of systemic arterial afterload in AS to improve outcomes.
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http://dx.doi.org/10.1016/j.hlc.2021.05.075DOI Listing
June 2021

Natural History of Patients with Ischemia and No Obstructive Coronary Artery Disease: The CIAO-ISCHEMIA Study.

Circulation 2021 Jun 1. Epub 2021 Jun 1.

New York University Grossman School of Medicine, New York, NY.

Ischemia with no obstructive coronary artery disease (INOCA) is common and has an adverse prognosis. We set out to describe the natural history of symptoms and ischemia in INOCA. CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in ISCHEMIA trial screen failures with INOCA) was an international cohort study conducted from 2014-2019 involving angina assessments (Seattle Angina Questionnaire [SAQ]) and stress echocardiograms 1-year apart. This was an ancillary study that included patients with history of angina who were not randomized in the ISCHEMIA trial. Stress-induced wall motion abnormalities were determined by an echocardiographic core laboratory blinded to symptoms, coronary artery disease (CAD) status and test timing. Medical therapy was at the discretion of treating physicians. The primary outcome was the correlation between changes in SAQ Angina Frequency score and change in echocardiographic ischemia. We also analyzed predictors of 1-year changes in both angina and ischemia, and compared CIAO participants with ISCHEMIA participants with obstructive CAD who had stress echocardiography before enrollment, as CIAO participants did. INOCA participants in CIAO were more often female (66% of 208 vs. 26% of 865 ISCHEMIA participants with obstructive CAD, p<0.001), but the magnitude of ischemia was similar (median 4 ischemic segments [IQR 3-5] both groups). Ischemia and angina were not significantly correlated at enrollment in CIAO (p=0.46) or ISCHEMIA stress echocardiography participants (p=0.35). At 1 year, the stress echocardiogram was normal in half of CIAO participants and 23% had moderate or severe ischemia (≥3 ischemic segments). Angina improved in 43% and worsened in 14%. Change in ischemia over one year was not significantly correlated with change in angina (rho=0.029). Improvement in ischemia and improvement in angina were common in INOCA, but not correlated. Our INOCA cohort had a similar degree of inducible wall motion abnormalities to concurrently enrolled ISCHEMIA participants with obstructive CAD. Our results highlight the complex nature of INOCA pathophysiology and the multifactorial nature of angina. URL: https://clinicaltrials.gov Unique Identifier: NCT02347215.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046791DOI Listing
June 2021

Enhancing the cardiovascular protective effects of a healthy dietary pattern with wolfberry (Lycium barbarum): A randomized controlled trial.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Department of Food Science & Technology, Faculty of Science, National University of Singapore, Singapore, Singapore.

Background: The consumption of wolfberry (Lycium barbarum), a rich source of carotenoids and bioactive polysaccharides, may serve as a potential dietary strategy for cardiovascular disease (CVD) risk management although limited studies examined its effects as whole fruits.

Objectives: To investigate the impact of wolfberry consumption as part of a healthy dietary pattern on vascular health-related outcomes and classical CVD risk factors in middle-aged and older adults in Singapore.

Methods: This is a 16-week, parallel design, randomized controlled trial. All participants (n = 40) received dietary counselling to follow healthy dietary pattern recommendations with the wolfberry group given additional instructions to cook and consume 15 g/d whole, dried wolfberry with their main meals. Biomarkers of vascular function (flow-mediated dilation, plasma total nitrate/nitrite, endothelin-1, and intercellular adhesion molecule-1), vascular structure (carotid intima-media thickness) and vascular regeneration (endothelial progenitor cell count, plasma angiopoietin 1 and angiopoietin 2), were assessed at baseline and postintervention. Serum lipid-lipoproteins and blood pressure were evaluated every 4 weeks.

Results: All participants showed an improved compliance toward the healthy dietary pattern. This was coupled with marked rises in total nitrate/nitrite concentrations (mean change wolfberry: 3.92 ± 1.73 nmol/mL; control: 5.01 ± 2.55 nmol/L) and reductions in endothelin-1 concentrations (wolfberry: -0.19 ± 0.06 pg/mL; control: -0.15 ± 0.08 pg/mL). Compared with the control which depicted no changes from baseline, the wolfberry group had a significantly higher HDL cholesterol (0.08 ± 0.04 mmol/L), as well as lower Framingham predicted long-term CVD risk (-0.8 ± 0.5%) and vascular age (-1.9 ± 1.0 y) postintervention. No differences were observed in the other vascular health-related outcomes.

Conclusions: In middle-aged and older adults, adherence to a healthy dietary pattern improves vascular tone. Incorporating wolfberry to the diet further improves blood lipid-lipoprotein profile and may lower long-term CVD risk. This study was registered at clinicatrials.gov as NCT03535844.
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http://dx.doi.org/10.1093/ajcn/nqab062DOI Listing
May 2021

Prognostic implications of left atrial dilation in aortic regurgitation due to bicuspid aortic valve.

Heart 2021 Apr 8. Epub 2021 Apr 8.

Department of Cardiology, Leiden University Medical Center, Leiden, Zuid-Holland, The Netherlands

Objective: To investigate the prognostic value of left atrial volume index (LAVI) in patients with moderate to severe aortic regurgitation (AR) and bicuspid aortic valve (BAV).

Methods: 554 individuals (45 (IQR 33-57) years, 80% male) with BAV and moderate or severe AR were selected from an international, multicentre registry. The association between LAVI and the combined endpoint of all-cause mortality or aortic valve surgery was investigated with Cox proportional hazard regression analyses.

Results: Dilated LAVI was observed in 181 (32.7%) patients. The mean indexed aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta diameters were 13.0±2.0 mm/m, 19.4±3.7 mm/m, 16.5±3.8 mm/m and 20.4±4.5 mm/m, respectively. After a median follow-up of 23 (4-82) months, 272 patients underwent aortic valve surgery (89%) or died (11%). When compared with patients with normal LAVI (<35 mL/m), those with a dilated LAVI (≥35 mL/m) had significantly higher rates of aortic valve surgery or mortality (43% and 60% vs 23% and 36%, at 1 and 5 years of follow-up, respectively, p<0.001). Dilated LAVI was independently associated with reduced event-free survival (HR=1.450, 95% CI 1.085 to 1.938, p=0.012) after adjustment for LV ejection fraction, aortic root diameter, LV end-diastolic diameter and LV end-systolic diameter.

Conclusions: In this large, multicentre registry of patients with BAV and moderate to severe AR, left atrial dilation was independently associated with reduced event-free survival. The role of this parameter for the risk stratification of individuals with significant AR merits further investigation.
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http://dx.doi.org/10.1136/heartjnl-2020-318907DOI Listing
April 2021

Plasma Clearance of B-Type Natriuretic Peptide (BNP) before and after Bariatric Surgery for Morbid Obesity.

Clin Chem 2021 Mar;67(4):662-671

Department of Cardiology, National University Heart Centre Singapore, National University Health System, Singapore.

Background: Obese patients have lower plasma concentrations of the cardiac natriuretic peptides (NPs) than their age- and sex-matched counterparts. This may reflect lower production and/or increased peptide clearance. It is unclear whether NP bioactivity is affected by obesity.

Methods: We studied the effects of obesity on B-type natriuretic peptide (BNP) clearance and bioactivity by comparing results from standardized intravenous infusions of BNP administered 2 weeks before and 6 months after bariatric surgery in 12 consecutive patients with morbid obesity (body mass index, BMI > 35 kg/m2). Anthropometric, clinical, neurohormonal, renal, and echocardiographic variables were obtained pre- and postsurgery. Pre- vs postsurgery calculated intrainfusion peptide clearances were compared.

Results: BMI (44.3 ± 5.0 vs 33.9 ± 5.2 kg/m2, P < 0.001) and waist circumference (130.3 ± 11.9 vs 107.5 ± 14.7 cm, P < 0.001) decreased substantially after bariatric surgery. Calculated plasma clearance of BNP was reduced (approximately 30%) after surgery. Though not controlled for, sodium intake was presumably lower after bariatric surgery. Despite this, preinfusion endogenous plasma NP concentrations did not significantly differ between pre- and postsurgery studies. The ratio of plasma N-terminal (NT)-proBNP to 24 h urine sodium excretion was higher postsurgery (P = 0.046; with similar nonsignificant findings for BNP, atrial NP (ANP) and NT-proANP), indicating increased circulating NPs for a given sodium status. Mean plasma NP concentrations for given calculated end-systolic wall stress and cardiac filling pressures (as assessed by echocardiographic E/e') rose slightly, but not significantly postsurgery. Second messenger, hemodynamic, renal, and neurohormonal responses to BNP were not altered between studies.

Conclusion: Obesity is associated with increased clearance, but preserved bioactivity, of BNP.
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http://dx.doi.org/10.1093/clinchem/hvaa308DOI Listing
March 2021

Adapting and embracing change in the new normal.

Singapore Med J 2021 Jan;62(1)

Editor-in-Chief, Singapore Medical Journal, Singapore.

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http://dx.doi.org/10.11622/smedj.2021006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027155PMC
January 2021

Inadequately low left ventricular mass in patients with significant aortic stenosis predicts favourable prognostic outcomes.

Int J Cardiovasc Imaging 2021 May 16;37(5):1611-1619. Epub 2021 Jan 16.

Department of Cardiology, National University Heart Centre Singapore, National University Health System, 1E Kent Ridge Rd, NUHS Tower Block, Level 9, Singapore, 119228, Singapore.

In patients with significant aortic stenosis (AS), the prognostic effect of the increase in left ventricular mass (LVM) in relation to one's hemodynamic load has been described. Inappropriately high LVM has been shown to predict adverse cardiovascular events. However, little is known about the prognostic impact of inadequately low LVM (i-lowLVM) in patients with significant AS. I-lowLVM was defined as the measured LVM < 73% of the predicted LVM based on sex, stroke work and height from the reference adult population, used in previous established studies. For outcome analysis, the end-point was defined as all-cause mortality, aortic valve replacement and/or admission for congestive heart failure. Kaplan-Meier curves and multivariable Cox regression models were constructed to compare outcomes on follow-up. During the follow-up (4.5 ± 4.1 years), 132 patients (11.1%) had i-lowLVM, 868 (73.1%) had adequate-LVM, 188 (15.8%) had inappropriately high LVM. Outcome analysis only included patients with i-lowLVM and adequate-LVM (N = 1000). An adverse composite event occurred in 41.7% of the i-lowLVM group and 52.4% of the adequate-LVM group (p = 0.021). Event-free survival in patients with i-lowLVM and appropriate-LVM was 76% versus 68% at 2-year, 55% versus 46% at 4-year, 33% versus 27% at 6-year, 20% versus 17% at 8-year, and 17% versus 11% at 10-year follow-up, respectively (p < 0.001). Cox analysis revealed that i-lowLVM was independently associated with lower composite adverse outcome (HR 0.624, 95% CI 0.460-0.846, p = 0.002) after adjusting for sex, age, ejection fraction, ischemic heart disease, diabetes and transaortic valve mean gradient. In the separate Cox subanalyses, the presence of i-lowLVM remained a predictor of lower composite adverse outcome in the severe AS subgroup (HR 0.587, 95% CI 0.396-0.870, p = 0.008), and the LVH subgroup (HR 0.574, 95% CI 0.401-0.824, p = 0.003) after adjusting for confounders. I-lowLVM despite significant AS may represent a distinct group that is associated with improved survival outcomes independent of other prognostic covariates.
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http://dx.doi.org/10.1007/s10554-020-02146-3DOI Listing
May 2021

Characteristics and outcomes of young patients with ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: retrospective analysis in a multiethnic Asian population.

Open Heart 2021 01;8(1)

Cardiology, National University Heart Centre, Singapore.

Objective: ST segment elevation myocardial infarction (STEMI) is associated with significant mortality leading to loss of productive life years, especially in younger patients. This study aims to compare the characteristics and outcomes of young versus older patients with STEMI undergoing primary percutaneous coronary intervention (PPCI) to help focus public health efforts in STEMI prevention.

Methods: Data from the Coronary Care Unit database of the National University Hospital, Singapore from July 2015 to June 2019 were reviewed. Patients were divided into young (<50 years old) or older (≥50 years old) groups.

Results: Of the 1818 consecutive patients with STEMI who underwent PPCI, 465 (25.6%) were <50 years old. Young compared with older patients were more likely to be male, current smokers, of Indian ethnicity, have family history of ischaemic heart disease (IHD) and had lower 1 year mortality (3.4% vs 10.4%, p<0.0001). Although diabetes, hypertension or dyslipidaemia was less common among young patients, the prevalence of having any one of these risk factors was high in the range of 28% to 38%. Age was an independent predictor of mortality in the older but not younger patients with STEMI, and diabetes showed a trend towards mortality in both groups.

Conclusion: Young patients with STEMI are more often smokers, of Indian ethnicity and had family history of IHD, although cardiometabolic risk factors are also prevalent. Mortality is lower, but not negligible, among the young patients with STEMI. Public health efforts are needed to reduce the prevalence of these risk factors among the constitutionally susceptible population.
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http://dx.doi.org/10.1136/openhrt-2020-001437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812097PMC
January 2021

Optimal vortex formation time index in mitral valve stenosis.

Int J Cardiovasc Imaging 2021 May 12;37(5):1595-1600. Epub 2021 Jan 12.

Department of Cardiology, National University Heart Centre, 1E Kent Ridge Rd, NUHS Tower Block, Level 9, Singapore, 119228, Singapore.

Left ventricular vortex formation time (VFT) is a novel dimensionless index of flow propagation during left ventricular diastole, which has been demonstrated to be useful in heart failure and cardiomyopathy. In mitral stenosis (MS), flow propagation in the LV may be suboptimal. We studied VFT in varying degrees of MS. Echocardiography was performed on 20 healthy controls and 50 cases of rheumatic MS. Patients with atrial fibrillation, LV ejection fraction < 50% and other valvular heart diseases were excluded. VFT was obtained using the length-to-diameter ratio (L/D), where L is the continuous-wave Doppler velocity time integral stroke distance, divided by D, the mitral leaflet separation index. This was correlated against varying degrees of MS severity, left atrial (LA) volume and function. In controls, VFT was 3.92 ± 2.00 (optimal range) and was higher (suboptimal) with increasing severity of mitral stenosis (4.98 ± 2.43 in mild MS; 7.22 ± 2.98 in moderate MS; 11.55 ± 2.67 in severe MS, p < 0.001). VFT negatively correlated with mitral valve area (R = 0.463, p < 0.001) and total LA emptying fraction (R = 0.348, p < 0.001), and positively correlated with LA volume index (R = 0.440, p < 0.001) and mean transmitral pressure gradient (R = 0.336, p < 0.001). More severe MS correlated with suboptimal (higher) VFT. The restricted mitral valve opening may disrupt vortex formation and optimal fluid propagation in the LV. Despite the compensatory increase in LA size with increasingly severe MS, reduced LA function also contributed to the suboptimal LV vortex formation.
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http://dx.doi.org/10.1007/s10554-020-02140-9DOI Listing
May 2021

The obesity paradox: association of obesity with improved survival in medically managed severe aortic stenosis.

Singapore Med J 2020 12 2. Epub 2020 Dec 2.

Department of Cardiology, National University Heart Centre Singapore, National University Health System, Singapore.

Introduction: The obesity paradox, where obesity is associated with improved survival, has been described in patients undergoing haemodialysis and in heart failure. It was also demonstrated in patients undergoing valve replacement for aortic stenosis (AS). We explored this phenomenon in medically managed severe AS.

Methods: 154 patients with medically managed severe AS (aortic valve area index [AVAi] < 0.6 cm2/m2; mean pressure gradient > 40 mmHg and peak velocity > 400 cm/s) and preserved left ventricular ejection fraction (> 50%) were categorised into the obese (body mass index [BMI] Asian cut-off ≥ 27.5 kg/m2) and non-obese groups. Their clinical and echocardiographic profiles were compared.

Results: 24 (15.6%) patients were obese. Obese patients were similar to non-obese patients in age (68.5 ± 11.6 vs. 68.9 ± 13.1 years) but had higher prevalence of cardiovascular risk factors. Left atrial diameter (43.7 ± 6.7 vs. 38.5 ± 10.2 mm) was larger in obese patients, while left ventricular outflow tract diameter (19.5 ± 1.7 vs. 20.4 ± 2.1 mm) was smaller. Despite lower AVAi in obese patients (0.36 ± 0.10 vs. 0.43 ± 0.11 cm2/m2), there was lower mortality (37.5% vs. 41.0%, log-rank 4.06, p = 0.045) on follow-up (8.0 ± 5.7 years). After adjusting for age and AVA, higher BMI ≥ 27.5 kg/m2 remained protective for mortality (hazard ratio 0.38, 95% confidence interval 0.15 to 0.98, p = 0.046).

Conclusion: We demonstrated that obesity was associated with improved survival in severe AS despite lower AVAi and increased prevalence of cardiovascular risk factors.
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http://dx.doi.org/10.11622/smedj.2020169DOI Listing
December 2020

ST-segment elevation myocardial infarction hospitalisations remain unchanged during COVID-19.

Singapore Med J 2020 Nov 30. Epub 2020 Nov 30.

Department of Cardiology, National University Heart Centre Singapore, Singapore.

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http://dx.doi.org/10.11622/smedj.2020157DOI Listing
November 2020

Electrocardiography findings in right ventricular apical pacing.

Singapore Med J 2020 Oct;61(10):517-522

Department of Cardiology, National Heart Centre Singapore, Singapore.

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http://dx.doi.org/10.11622/smedj.2020148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930312PMC
October 2020

Singapore Medical Journal in the age of social media.

Singapore Med J 2020 Oct;61(10):501-502

Singapore Medical Journal.

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http://dx.doi.org/10.11622/smedj.2020142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930315PMC
October 2020

Cost-Effectiveness of Transcatheter Aortic Valve Implantation in Intermediate and Low Risk Severe Aortic Stenosis Patients in Singapore.

Ann Acad Med Singap 2020 Jul;49(7):423-433

Department of Cardiology, National University Heart Centre, Singapore.

Introduction: Singapore has the world's second most efficient healthcare system while costing less than 5% GDP. It remains unclear whether transcatheter aortic valve implantation (TAVI) is cost-effective for treating intermediate-low risk severe aortic stenosis (AS) patients in a highly efficient healthcare system.

Materials And Methods: A two-phase economic model combining decision tree and Markov model was developed to assess the costs, effectiveness, and the incremental cost-effectiveness ratio (ICER) of transfemoral (TF) TAVI versus surgical aortic valve replacement (SAVR) in intermediate-low risk patients over an 8-year time horizon. Mortality and complications rates were based on PARTNER 2 trial cohort A and Singapore life table. Costs were mainly retrieved from Singapore National University Health System database. Health utility data were obtained from Singapore population based on the EuroQol-5D (EQ-5D). A variety of sensitivity analyses were conducted.

Results: In base case scenario, the incremental effectiveness of TF-TAVI versus SAVR was 0.19 QALYs. The ICER of TF-TAVI was S$33,833/QALY. When time horizon was reduced to 5 years, the ICER was S$60,825/QALY; when event rates from the propensity analysis was used, the ICER was S$21,732/QALY and S$44,598/QALY over 8-year and 5-year time horizons, respectively. At a willingness to pay threshold of S$73,167/QALY, TF-TAVI had a 98.19% probability of being cost-effective after 100,000 simulations. The model was the most sensitive to the costs of TF-TAVI procedure.

Conclusion: TF-TAVI is a highly cost-effective option compared to SAVR for intermediate-low risk severe AS patients from a Singapore healthcare system perspective. Increased procedure experience, reduction in device cost, and technology advance may have further increased the cost-effectiveness of TF-TAVI per scenario analysis.
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July 2020

Lipid-lowering treatment and low-density lipoprotein cholesterol target achievement in patients with type 2 diabetes and acute coronary syndrome.

Arch Cardiovasc Dis 2020 Oct 29;113(10):617-629. Epub 2020 Aug 29.

Stiftung Institut für Herzinfarktforschung, 67063 Ludwigshafen am Rhein, Germany; Klinikum der Stadt Ludwigshafen, Medizinische Klinik B, 67063 Ludwigshafen am Rhein, Germany.

Background: Patients with type 2 diabetes mellitus characteristically display an atherogenic lipid profile with high triglyceride concentrations, low high-density lipoprotein cholesterol (HDL-C) concentrations and low-density lipoprotein cholesterol (LDL-C) concentrations not always elevated. It is unclear if patients with diabetes who present with an acute coronary syndrome (ACS) receive different or more-potent lipid-lowering therapy (LLT).

Aims: To investigate lipid abnormalities in patients with and without type 2 diabetes hospitalised for an ACS, and use of LLT before admission and 4 months after the event.

Methods: Patients were included in the observational DYSIS II study if they were hospitalised for an ACS and had a full lipid profile.

Results: Of 3803 patients, diabetes was documented in 1344 (54.7%). Compared to patients without diabetes, those with diabetes had a lower mean LDL-C (101.2 vs. 112.0mg/dL; 2.6 vs. 2.9mmol/L; P<0.0001), with a greater proportion attaining concentrations<70mg/dL (1.8mmol/L) (23.9% vs. 16.0%; P<0.0001) and<55mg/dL (1.4mmol/L) (11.3% vs. 7.3%; P<0.0001), a higher mean triglyceride concentration (139.0 vs. 121.0mg/dL; 1.6 vs. 1.4mmol/L; P<0.0001) and a lower HDL-C concentration. LLT was more commonly given to patients with diabetes (77.5% vs. 58.8%; P<0.0001); there were no differences in types of therapy prescribed. Four months after hospitalisation, most patients from both groups were being treated with LLT (predominantly statin monotherapy).

Conclusions: Despite the different lipid profiles, the type of LLT prescribed did not vary depending on the presence or absence of type 2 diabetes. There was no difference in LLT in patients with and without diabetes at 4-month follow-up, except for fibrates, which were used in 2% of patients with and 1% of patients without diabetes. Statin monotherapy of intermediate potency was the predominant treatment in both groups.
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http://dx.doi.org/10.1016/j.acvd.2020.05.013DOI Listing
October 2020

COVID-19: local lessons from a global pandemic.

Singapore Med J 2020 07 26;61(7):341-342. Epub 2020 Jun 26.

Department of Cardiology, National University Heart Centre Singapore, Singapore.

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http://dx.doi.org/10.11622/smedj.2020097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926598PMC
July 2020

Comparison of Clinical and Echocardiographic Features of Asymptomatic Patients With Stenotic Bicuspid Versus Tricuspid Aortic Valves.

Am J Cardiol 2020 08 16;128:210-215. Epub 2020 May 16.

Department of Cardiology, National University Heart Centre, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

The clinical and imaging differences between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with medically managed asymptomatic moderate-to-severe aortic stenosis (AS) have not been studied previously. We aim to characterize these differences and their clinical outcomes in this study. A retrospective observational study was conducted on 836 consecutive cases of isolated asymptomatic moderate-to-severe AS, with median follow-up of 3.4 years. Clinical and echocardiographic characteristics were compared between BAV and TAV patients. Subgroup analysis stratified by AS severity were performed. Survival analysis of all-cause mortality was performed using Kaplan-Meier curves and Cox proportional hazards model. Compared to BAV patients, TAV patients were older (76 ± 11 vs 55 ± 16 years, p <0.001) and had more co-morbidities including hypertension (78% vs 56%; p <0.001), diabetes (41% vs 24%; p <0.001), and chronic kidney disease (20% vs 3%; p = 0.001). TAV patients had less severe aortic valve disease than BAV patients, with a higher aortic valve area index (0.71 ± 0.20 cm/m vs 0.61 ± 0.18 cm/m, p <0.001) and less aortic dilation (sinotubular junction: 23.7 ± 4.0 mm vs 26.9 ± 4.8 mm, p <0.001; mid-ascending aorta: 31.4 ± 4.7 mm vs 36.3 ± 6.3 mm, p <0.001). TAV patients were more likely to have eccentric left ventricular hypertrophy and less likely to have a normal geometry (p = 0.003). Competing risk analysis identified increased age (hazard ratio 1.03, 95% confidence interval 1.02 to 1.05, p <0.001) and LVEF (hazard ratio 0.98, 95% confidence interval 0.97 to 0.99, p <0.001) as independent risk factors of all-cause mortality. Valve morphology was not a significant independent risk factor for aortic valve replacement or mortality. In conclusion, asymptomatic TAV patients had more cardiovascular risk factors, less severe aortic valve disease, less sinotubular and mid-ascending aortic dilation, more severe LV remodeling.
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http://dx.doi.org/10.1016/j.amjcard.2020.05.008DOI Listing
August 2020

Novel Echocardiography-Derived Left Ventricular Stiffness Index in Low-Flow Versus Normal-Flow Severe Aortic Stenosis with Preserved Left Ventricular Ejection Fraction.

Sci Rep 2020 06 3;10(1):9086. Epub 2020 Jun 3.

Department of Cardiology, National University Heart Centre Singapore, National University Health System, Singapore, Singapore.

Background Paradoxical low-flow (LF) severe aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF) may have poorer prognosis than normal-flow (NF) AS, though its pathophysiology remained unclear. In particular, LV stiffness has not been compared between LF vs NF. We used a novel echocardiography-derived index of LV stiffness to compare between these groups. Consecutive patients with medically-managed isolated severe AS (aortic valve area < 1 cm) and preserved LVEF (>50%) were studied. Echocardiographic LV stiffness index was measured by a method previously validated against cardiac catheterization. We compared LF (stroke volume index, SVI < 35 ml/m) and NF severe AS. Of the 352 patients, 121 (34%) were LF. Both LF and NF groups had similar demographics, valve areas and indices. Compared to NF, LF severe AS had higher LV stiffness indices (>0.11 ml OR 3.067, 95% CI 1.825-5.128, p < 0.001). Increased LV stiffness was associated with concentric remodelling and more severe diastolic dysfunction, especially in LF AS. An LV stiffness index of > 0.11 ml was independently associated with increased mortality, after adjusting for age, clinical and echocardiographic parameters (HR 2.283 95% CI 1.318-3.968, p = 0.003). Non-invasive echocardiographic-derived index of LV stiffness may be important in LF AS. Increased LV stiffness was related to LV concentric remodelling and diastolic dysfunction, and associated with poorer clinical outcomes in medically-managed AS.
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http://dx.doi.org/10.1038/s41598-020-65758-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270100PMC
June 2020

Differences in Clinical and Echocardiographic Profiles and Outcomes of Patients With Atrial Fibrillation Versus Sinus Rhythm in Medically Managed Severe Aortic Stenosis and Preserved Left Ventricular Ejection Fraction.

Heart Lung Circ 2020 Dec 14;29(12):1773-1781. Epub 2020 Apr 14.

Department of Cardiology, National University Heart Centre, Singapore, National University Health System, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Background: Atrial fibrillation (AF) results in the loss of atrial booster pump function and portends poorer outcome in aortic valve stenosis (AS). However, its characteristics and impact on medically managed AS remained under-recognised. We compared these patients with AF to sinus rhythm (SR).

Method: In total, 347 consecutive patients with medically managed severe AS (aortic valve area <1 cm) and preserved left ventricular ejection fraction (>50%) were studied, in terms of echocardiographic characteristics and clinical outcomes. Appropriate univariate and multivariate models were used, while Kaplan-Meier curves and Cox regression models were constructed to compare clinical outcomes (mortality, admissions for congestive cardiac failure, and stroke).

Results: Ninety (90) (25.9%) patients had AF. Patients with AF had lower body mass index (BMI 18.5±10.4 vs 23.8±6.2 g/m; p<0.001), larger left ventricular mass index (LVMI 127.9±39.0 vs 116.7±36.5; p=0.017), and left atrial volume index (53.2±20.0 vs 31.0±9.2 mL/m; p=0.004). Atrial fibrillation was associated with higher mortality (52.2% vs 37.4%; Kaplan-Meier log-rank 7.18; p=0.007), admissions for congestive cardiac failure (log-rank 6.42; p=0.011), and poorer composite outcomes (log-rank 6.29; p=0.012). The incidence of stroke in both groups were similar on follow-up (log-rank 0.08; p=0.776). After adjusting for age, BMI, LVMI, and left atrial volume index on Cox regression, AF remained independently associated with poorer composite clinical outcomes (hazard ratio, 1.66; 95% confidence interval 1.07-2.58).

Conclusions: Atrial fibrillation remained an important comorbidity affecting a quarter of patients with medically managed severe AS. It was independently associated with poorer clinical outcomes and may thus aid in prognostication and management.
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http://dx.doi.org/10.1016/j.hlc.2020.02.018DOI Listing
December 2020

A new non-invasive index for prognosis evaluation in patients with aortic stenosis.

Sci Rep 2020 04 30;10(1):7333. Epub 2020 Apr 30.

National University Heart Centre Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 9, Singapore, 119228, Singapore.

The global left ventricular (LV) contractility index, dσ*/dt measures the maximal rate of change in pressure-normalized LV wall stress. We aim to describe the trend of dσ*/dt in differing severity of aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF) and the association of dσ*/dt with clinical outcomes in moderate AS and severe AS. We retrospectively studied a total of 1738 patients with AS (550 mild AS, 738 moderate AS, 450 severe AS) and preserved LVEF ≥ 50% diagnosed from 1 January 2001 to 31 December 2015. dσ*/dt worsened with increasing severity of AS despite preserved LVEF (mild AS: 3.69 ± 1.28 s, moderate AS: 3.17 ± 1.09 s, severe AS: 2.58 ± 0.83 s, p < 0.001). Low dσ*/dt < 2.8 s was independently associated with a higher composite outcome of aortic valve replacement, congestive cardiac failure admissions and all-cause mortality (adjusted hazard ratio 1.48, 95% CI: 1.25-1.77, p < 0.001). In conclusion, dσ*/dt declined with worsening AS despite preserved LVEF. Low dσ*/dt < 2.8 s was independently associated with adverse clinical outcomes in moderate AS and severe AS with preserved LVEF.
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http://dx.doi.org/10.1038/s41598-020-63777-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193646PMC
April 2020

Significant aortic stenosis associated with poorer functional outcomes in patients with acute ischaemic stroke undergoing endovascular therapy.

Interv Neuroradiol 2020 Dec 27;26(6):793-799. Epub 2020 Apr 27.

Division of Neurology, Department of Medicine, National University Health System, Singapore, Singapore.

Background And Aim: Bi-directional feedback mechanisms exist between the heart and brain, which have been implicated in heart failure. We postulate that aortic stenosis may alter cerebral haemodynamics and influence functional outcomes after endovascular thrombectomy for acute ischaemic stroke. We compared clinical characteristics, echocardiographic profile and outcomes in patients with or without aortic stenosis that underwent endovascular thrombectomy for large vessel occlusion acute ischaemic stroke.

Methods: Consecutive acute ischaemic stroke patients with anterior and posterior circulation large vessel occlusion (internal carotid artery, middle cerebral artery and basilar artery) who underwent endovascular thrombectomy were studied. Patients were divided into those with significant aortic stenosis (aortic valve area <1.5 cm) and without. Univariate and multivariate analyses were employed to compare and determine predictors of functional outcomes measured by modified Rankin scale at three months.

Results: We identified 26 (8.5%) patients with significant aortic stenosis. These patients were older (median age 76 (interquartile range 68-84) vs. 67 (interquartile range 56-75) years,  = 0.001), but similar in terms of medical comorbidities and echocardiographic profile. Rates of successful recanalisation (73.1% vs. 78.0%), symptomatic intracranial haemorrhage (7.7% and 7.9%) and mortality (11.5% vs. 12.6%) were similar. Significant aortic stenosis was independently associated with poorer functional outcome (modified Rankin scale >2) at three months (adjusted odds ratio 2.7, 95% confidence interval 1.1-7.5,  = 0.048), after adjusting for age, door-to-puncture times, stroke severity and rates of successful recanalisation.

Conclusion: In acute ischaemic stroke patients managed with endovascular thrombectomy, significant aortic stenosis is associated with poor functional outcome despite comparable recanalisation rates. Larger cohort studies are needed to explore this relationship further.
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http://dx.doi.org/10.1177/1591019920920988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724604PMC
December 2020

Controversies and discrepancies in the effect of dietary fat and cholesterol on cardiovascular risk.

Singapore Med J 2021 Feb 21;62(2):56-62. Epub 2020 Apr 21.

Department of Cardiology, National University Heart Centre Singapore, Singapore.

Cardiovascular disease (CVD) is the leading cause of death worldwide. The top ten causes of death in Singapore include many cardiovascular-related diseases such as ischaemic heart disease. The increasing prevalence of CVD poses a burden to both the economy and healthcare system of a country. Dietary habits, in particular dietary fats and cholesterol intake, have been shown to greatly influence CVD risks. Therefore, reference and adherence to relevant dietary guidelines could be crucial in CVD prevention. Recent research findings have provided novel insights into the relationship between certain dietary fats or cholesterol intake and CVD risks, challenging or reinforcing previous guidelines. These findings may, however, be conflicting, and there are still controversies over the effects of dietary fats and cholesterol as well as their association with cardiovascular risk. This review paper aims to evaluate common controversies, identify gaps in relevant research areas and summarise evidence-based dietary recommendations.
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http://dx.doi.org/10.11622/smedj.2020065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027141PMC
February 2021

Transplantation of Endothelial Progenitor Cells in Obese Diabetic Rats Following Myocardial Infarction: Role of Thymosin Beta-4.

Cells 2020 04 12;9(4). Epub 2020 Apr 12.

National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore 169609, Singapore.

Endothelial progenitor cells (EPCs) are bone-marrow derived cells that are critical in the maintenance of endothelial wall integrity and protection of ischemic myocardium through the formation of new blood vessels (vasculogenesis) or proliferation of pre-existing vasculature (angiogenesis). Diabetes mellitus (DM) and the metabolic syndrome are commonly associated with ischemic heart disease through its pathological effects on the endothelium and consequent endothelial dysfunction. Thymosin-β4 (Tβ4) which expressed in the embryonic heart is critical in epicardial and coronary artery formation. In this study, we explored the effects of Tβ4 treatment on diabetic EPCs in vitro and intramyocardial injection of Tβ4-treated and non-Tβ4 treated EPCs following acute myocardial infarction (MI) of diabetic rats in vivo. It was found that 10 ng/mL Tβ4 increased migration, tubule formation, and angiogenic factor secretion of diabetic EPCs in vitro. In vivo, although implantation of Tβ4 treated diabetic EPCs significantly increased capillary density and attracted more c-Kit positive progenitor cells into the infarcted hearts as compared with implantation of non-Tβ4 treated diabetic EPCs, the significantly improved left ventricular ejection fraction was only found in the rats which received non-Tβ4 treated EPCs. The data suggests that a low dose Tβ4 increases diabetic EPC migration, tubule formation, and angiogenic factor secretion. However, it did not improve the effects of EPCs on left ventricular pump function in diabetic rats with MI.
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http://dx.doi.org/10.3390/cells9040949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226991PMC
April 2020

Long-term effects of bariatric surgery on cardiovascular risk factors in Singapore.

Singapore Med J 2020 Apr 3. Epub 2020 Apr 3.

Department of Cardiology, National University Heart Centre, National University Health System, Singapore

Introduction: Bariatric surgery is considered an effective treatment for weight loss and improving the metabolic profile of obese patients. Obesity-related comorbidities such as hyperlipidaemia and type 2 diabetes mellitus (DM) are significant cardiovascular risk factors. Additionally, statins have increased the onset of DM in prospective clinical trials, and many obese patients are on statins. We retrospectively examined the effect of bariatric surgery on lipid profile, DM control and weight loss at five years’ follow-up.

Methods: A total of 104 patients (n = 104) undergoing bariatric surgery in 2008–2012 were retrospectively studied. 36 patients were on preoperative statins. Their lipid profile, DM control and weight loss were examined at the one-year and five-year follow-up.

Results: Both high-density lipoprotein (HDL) and triglyceride levels showed significant improvement at the one-year and five-year follow-up (p = 0.01). Total cholesterol showed significant improvement at the one-year follow-up (−0.30 mmol/dL, p = 0.0338); however, better control was not sustained at the five-year follow-up (−0.15 mmol/dL, p = 0.133). Low-density lipoprotein did not show any considerable improvement at the one- and five-year follow-up (−0.27 mmol/dL, p = 0.150; −0.24 mmol/dL, p = 0.138, respectively). There was a statistically significant improvement in DM control in these patients and in those on preoperative statins. Weight loss was sustained at one and five years.

Conclusion: Bariatric surgery does not confer a uniform improvement in lipid profile in the long term. It does, however, induce efficient weight loss and improvement in diabetic profile, even in those on preoperative statins.
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http://dx.doi.org/10.11622/smedj.2020047DOI Listing
April 2020

At the 'heart' of the COVID-19 outbreak: early cardiac implications and mitigating strategies.

Singapore Med J 2020 07 31;61(7):373-374. Epub 2020 Mar 31.

Department of Cardiology, National University Heart Centre Singapore, Singapore.

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http://dx.doi.org/10.11622/smedj.2020042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926610PMC
July 2020

A myriad of electrocardiographic findings associated with digoxin use.

Singapore Med J 2020 Jan;61(1):9-14

Department of Cardiology, National University Heart Centre Singapore.

Digoxin is a commonly prescribed drug in the management of heart failure and atrial fibrillation. Despite its widespread use, most clinicians have little experience with recognising clinical signs and symptoms that might suggest a potentially lethal drug toxicity. We herein describe two cases with specific reference to the electrocardiographic changes induced by digoxin and discuss the predisposing factors for toxicity, recognition of possible toxicity and treatment approaches.
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http://dx.doi.org/10.11622/smedj.2020005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900815PMC
January 2020

Doing our part for medical education.

Authors:
Kian Keong Poh

Singapore Med J 2020 01;61(1)

A/Prof Poh Kian Keong, Editor-in-Chief, Singapore Medical Journal, 2985 Jalan Bukit Merah, #02-2C, SMF Building, Singapore.

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http://dx.doi.org/10.11622/smedj.2020001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900813PMC
January 2020

Echocardiographic discrepancies in severity grading of aortic valve stenosis with left ventricular outflow tract (LVOT) cut-off values in an Asian population.

Int J Cardiovasc Imaging 2020 Apr 2;36(4):615-621. Epub 2020 Jan 2.

Department of Cardiology, National University Heart Centre Singapore, National University Health System, Singapore, Singapore.

Inconsistencies in grading of aortic stenosis (AS) severity have been reported. However, it remains to be studied in an Asian population. We investigated consistency of grading AS severity at various left ventricular outflow tract diameter (LVOTd) categories, and postulated alternative cut-offs for more consistent grading of AS severity. Consecutive Asian patients (n = 350) with index echocardiographic diagnosis of severe AS were divided them into three groups based on LVOTd: 'small' (< 20 mm), 'average' (20-22 mm) and 'large' (> 22 mm). In each group, the consistency of flow-dependent (transaortic mean pressure gradient (MG)) and flow-independent parameters (AVA) were used for classification of AS severity. Of 350 patients, 51.7% had small LVOTd, while 30.8% and 17.5% had average and large LVOTd respectively. Consistent grading by LVOTd based on AVA and MG, was seen in 33.7% of patients with small, 47.6% with average, 57.7% with large LVOTd. When an AVA cut-off of 0.9 cm was used, consistent grading improved to 38.0% in small, 56.5% in average and 70.0% in large LVOTd. At an AVA cut-off of 0.8 cm, there was further incremental improvement in the small LVOTd group to 54.1% (p < 0.05). In conclusion, current severe AS guidelines are most inconsistent with those in the small LVOTd group. With majority of the study's Asian population having small LVOTd, this raises concerns that current AS guidelines may overestimate the severity of AS in the Asian cohort. Improved consistency in echocardiographic grading may be attained with a lower AVA cut-off in this Asian cohort.
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http://dx.doi.org/10.1007/s10554-019-01755-xDOI Listing
April 2020

Reducing reperfusion injury during percutaneous coronary intervention.

Singapore Med J 2019 12;60(12):608-609

Department of Cardiology, National University Heart Centre Singapore, National University Health System, Singapore.

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http://dx.doi.org/10.11622/smedj.2019157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911062PMC
December 2019