Publications by authors named "Hui Wen Sim"

24 Publications

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An Asian Perspective on Gender Differences in In-Hospital and Long-Term Outcome of Cardiac Mortality and Ischemic Stroke after Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction.

J Stroke Cerebrovasc Dis 2021 Nov 20;31(1):106215. Epub 2021 Nov 20.

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

Objectives: Gender differences historically exist in cardiovascular disease, with women experiencing higher rates of major adverse cardiovascular events. We investigated these trends in a contemporary Asian cohort, examining the impact of gender differences on cardiac mortality and ischemic stroke after primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI).

Materials And Methods: We analysed 3971 consecutive patients who underwent primary PCI for STEMI retrospectively. The primary outcome was cardiac mortality and ischemic stroke in-hospital, at one year and on longer-term follow up (median follow up 3.62 years, interquartile range 1.03-6.03 years).

Results: There were 580 (14.6%) female patients and 3391 (85.4%) male patients. Female patients were older and had higher prevalence of hypertension, diabetes, previous strokes, and chronic kidney disease. Cardiac mortality was higher in female patients during in-hospital (15.5% vs. 6.2%), 1-year (17.4% vs. 7.0%) and longer term follow up (19.9% vs. 8.1%, log-rank test: p < 0.001). Similarly, females had higher incidence of ischemic stroke at in-hospital (2.6% vs. 1.0%), 1-year (3.6% vs. 1.4%) and in the longer-term (6.7% vs. 3.1%) as well (log-rank test: p < 0.001). Female gender remained an independent predictor of in-hospital cardiac mortality (HR 1.395, 95%CI 1.061-1.833, p=0.017) and on longer-term follow-up (HR 1.932 95%CI 1.212-3.080, p=0.006) even after adjusting for confounders.

Conclusions: Females were at higher risk of in-hospital and long-term cardiac mortality and ischemic stroke after PPCI for STEMI. Future studies are warranted to investigate the role of aggressive management of cardiovascular risk factors and follow-up to improve outcomes in the females with STEMI.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106215DOI Listing
November 2021

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

Long-term clinical outcomes of biodegradable polymer drug eluting stents versus second-generation durable polymer drug eluting stents for ST-segment elevation myocardial infarction.

Cardiovasc Revasc Med 2021 Apr 16. Epub 2021 Apr 16.

National University Heart Center, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Background: Biodegradable polymer drug eluting stents (BP-DES) may offer the advantage of vascular healing in ST-segment elevation myocardial infarction (STEMI). Long-term outcome data comparing BP-DES and second-generation durable polymer drug eluting stents (DP-DES) in STEMI is lacking. This study aims to compare the long-term clinical outcomes of BP-DES versus second-generation DP-DES in STEMI.

Methods: This is an observational study of consecutive patients with STEMI who received either BP-DES (n = 854) or DP-DES (n = 708) during primary percutaneous coronary intervention (PCI) from 1st February 2007 to 31st December 2016. The primary outcome was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (MI), and target lesion revascularization with follow up till 30th November 2019.

Results: The baseline demographics, lesion and procedural characteristic were similar between the two groups except for more prior MI and chronic obstructive pulmonary disease in the BP-DES group. At a median follow up of 4.2 years (interquartile range: 2.6-6.2 years), the incidence of TLF was similar between BP-DES and DP-DES (adjusted hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.70-1.26). Likewise, incidence of major adverse cardiovascular events (MACE: all-cause death, any MI or target vessel revascularization) and definite stent thrombosis were similar in both groups (MACE: adjusted HR 1.04, 95% CI 0.82-1.32; definite stent thrombosis: adjusted HR 1.06, 95% CI 0.31-3.64).

Conclusion: Among patients with STEMI who underwent primary PCI, BP-DES and DP-DES implantation was associated with similar long-term clinical outcomes.
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http://dx.doi.org/10.1016/j.carrev.2021.04.014DOI Listing
April 2021

Long-Term Outcomes of Stroke or Transient Ischemic Attack after Non-Emergency Percutaneous Coronary Intervention.

J Stroke Cerebrovasc Dis 2021 Jul 14;30(7):105786. Epub 2021 Apr 14.

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

Objectives: Non-emergency percutaneous coronary intervention (PCI) has lower risk of stroke than emergency PCI. With increasing elective PCI and increasing risk of stroke after PCI, risk factors for stroke or transient ischaemic attack (TIA) in non-emergency PCI and long-term outcomes needs to be better characterised. We aim to identify risk factors for cerebrovascular accidents in patients undergoing non-emergency PCI and long-term outcomes after stroke or TIA.

Materials And Methods: A retrospective cohort study was performed on 1724 consecutive patients who underwent non-emergency PCI for non-ST-segment elevation myocardial infarction (NSTEMI), unstable and stable angina. The primary outcomes measured were stroke or TIA, myocardial infarction (MI) and all-cause death.

Results: Upon mean follow-up of 3.71 (SD 0.97) years, 70 (4.1%) had subsequent ischaemic stroke or TIA, and they were more likely to present with NSTEMI (50 [71.4%] vs 892 [54.0%], OR 2.13 [1.26-3.62], p = 0.004) and not stable angina (19 [27.1%] vs 648 [39.2%], OR 0.58 [0.34-0.99]). Femoral access was associated with subsequent stroke or TIA compared to radial access (OR 2.10 [1.30-3.39], p < 0.002). Previous stroke/TIA was associated with subsequent stroke/TIA (p < 0.001), death (p < 0.001) and MI (p = 0.002). Furthermore, subsequent stroke/TIA was significantly associated with subsequent MI (p = 0.006), congestive cardiac failure (CCF) (p = 0.008) and death (p < 0.001).

Conclusions: In patients undergoing non-emergency PCI, previous stroke/TIA predicted post-PCI ischaemic stroke/TIA, which was associated with death, MI, CCF.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105786DOI Listing
July 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

Remote Postdischarge Treatment of Patients With Acute Myocardial Infarction by Allied Health Care Practitioners vs Standard Care: The IMMACULATE Randomized Clinical Trial.

JAMA Cardiol 2021 Jul;6(7):830-835

Cardiovascular Research Institute, Yong Loo-Lin School of Medicine, National University of Singapore, Singapore.

Importance: There are few data on remote postdischarge treatment of patients with acute myocardial infarction.

Objective: To compare the safety and efficacy of allied health care practitioner-led remote intensive management (RIM) with cardiologist-led standard care (SC).

Design, Setting, And Participants: This intention-to-treat feasibility trial randomized patients with acute myocardial infarction undergoing early revascularization and with N-terminal-pro-B-type natriuretic peptide concentration more than 300 pg/mL to RIM or SC across 3 hospitals in Singapore from July 8, 2015, to March 29, 2019. RIM participants underwent 6 months of remote consultations that included β-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-I/ARB) dose adjustment by a centralized nurse practitioner team while SC participants were treated face-to-face by their cardiologists.

Main Outcomes And Measures: The primary safety end point was a composite of hypotension, bradycardia, hyperkalemia, or acute kidney injury requiring hospitalization. To assess the efficacy of RIM in dose adjustment of β-blockers and ACE-I/ARBs compared with SC, dose intensity scores were derived by converting comparable doses of different β-blockers and ACE-I/ARBs to a scale from 0 to 5. The primary efficacy end point was the 6-month indexed left ventricular end-systolic volume (LVESV) adjusted for baseline LVESV.

Results: Of 301 participants, 149 (49.5%) were randomized to RIM and 152 (50.5%) to SC. RIM and SC participants had similar mean (SD) age (55.3 [8.5] vs 54.7 [9.1] years), median (interquartile range) N-terminal-pro-B-type natriuretic peptide concentration (807 [524-1360] vs 819 [485-1320] pg/mL), mean (SD) baseline left ventricular ejection fraction (57.4% [11.1%] vs 58.1% [10.3%]), and mean (SD) indexed LVESV (32.4 [14.1] vs 30.6 [11.7] mL/m2); 15 patients [5.9%] had a left ventricular ejection fraction <40%. The primary safety end point occurred in 0 RIM vs 2 SC participants (1.4%) (P = .50). The mean β-blocker and ACE-I/ARB dose intensity score at 6 months was 3.03 vs 2.91 (adjusted mean difference, 0.12 [95% CI, -0.02 to 0.26; P = .10]) and 2.96 vs 2.77 (adjusted mean difference, 0.19 [95% CI, -0.02 to 0.40; P = .07]), respectively. The 6-month indexed LVESV was 28.9 vs 29.7 mL/m2 (adjusted mean difference, -0.80 mL/m2 [95% CI, -3.20 to 1.60; P = .51]).

Conclusions And Relevance: Among low-risk patients with revascularization after myocardial infarction, RIM by allied health care professionals was feasible and safe. There were no differences in achieved medication doses or indices of left ventricular remodeling. Further studies of RIM in higher-risk cohorts are warranted.

Trial Registration: ClinicalTrials.gov Identifier: NCT02468349.
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http://dx.doi.org/10.1001/jamacardio.2020.6721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774042PMC
July 2021

Sleep apnea and diabetes mellitus are independently associated with cardiovascular events and hospitalization for heart failure after coronary artery bypass grafting.

Sci Rep 2020 12 10;10(1):21664. Epub 2020 Dec 10.

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

The relative and combined effects of sleep apnea with diabetes mellitus (DM) on cardiovascular outcomes in patients undergoing coronary artery bypass grafting (CABG) remain unknown. In this secondary analysis of data from the SABOT study, 1007 patients were reclassified into four groups based on their sleep apnea and DM statuses, yielding 295, 218, 278, and 216 patients in the sleep apnea (+) DM (+), sleep apnea (+) DM (-), sleep apnea (-) DM (+), and sleep apnea (-) DM (-) groups, respectively. After a mean follow-up period of 2.1 years, the crude incidence of major adverse cardiac and cerebrovascular event was 18% in the sleep apnea (+) DM (+), 11% in the sleep apnea (+) DM (-), 13% in the sleep apnea (-) DM (+), and 5% in the sleep apnea (-) DM (-) groups. Using sleep apnea (-) DM (-) as the reference group, a Cox regression analysis indicated that sleep apnea (+) and DM (+) independently predicted MACCEs (adjusted hazard ratio, 3.2; 95% confidence interval, 1.7-6.2; p = 0.005) and hospitalization for heart failure (adjusted hazard ratio, 12.6; 95% confidence interval, 3.0-52.3; p < 0.001). Sleep apnea and DM have independent effects on the prognosis of patients undergoing CABG.Clinical trial registration: ClinicalTrials.gov identification no. NCT02701504.
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http://dx.doi.org/10.1038/s41598-020-78700-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730381PMC
December 2020

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

The impact of chronic kidney disease on long-term outcomes following semi-urgent and elective percutaneous coronary intervention.

Coron Artery Dis 2021 Sep;32(6):517-525

Department of Cardiology, National University Heart Centre.

Introduction: The effects of chronic kidney disease (CKD) on outcomes in patients undergoing semi-urgent and elective percutaneous coronary intervention (PCI) are unclear. This study aims to investigate impact of CKD on long-term outcomes of this population.

Methods: This was a retrospective cohort study of patients who underwent semi-urgent and elective PCI from 1 January 2014 to 31 December 2015 at a tertiary academic center. They were stratified into five groups - group 1 [estimated glomerular filtration rate (eGFR) ≥90 ml/min/1.73m2], group 2 (eGFR 60-89 ml/min/1.73m2), group 3 (eGFR 30-59 ml/min/1.73 m2), group 4 (eGFR <30 ml/min/1.73m2), and group 5 (dialysis). Demographics, risk factors in relation to endpoints of all-cause mortality, contrast-induced nephropathy (CIN), three-point major adverse cardiac events (MACE) (cardiac death, subsequent myocardial infarction, subsequent stroke), and four-point MACE (including target lesion revascularization) were analyzed.

Results: One thousand six hundred nine patients were included. Advanced CKD patients were more likely to be female and older, with higher prevalence of co-morbidities. Compared to group 1, group 4 patients were associated with increased risk of three-point [adjusted hazard ratio (aHR) 1.94, 95% confidence interval (CI): 1.06-3.55; P = 0.031] and four-point MACE (aHR 2.15, 95% CI: 1.21-3.80; P = 0.009). However, higher contrast volume usage [odds ratio (OR) 2.20, 95% CI: 1.04-4.68; P = 0.040) was associated with increased CIN risk but not reduced eGFR (OR 1.62, 95% CI: 0.57-4.65; P = 0.369).

Conclusion: Advanced CKD patients undergoing PCI were associated with higher co-morbid burden. Despite adjustments for co-morbidities, these patients had higher mortality and worse cardiovascular outcomes at 3 years following contemporary PCI.
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http://dx.doi.org/10.1097/MCA.0000000000000980DOI Listing
September 2021

Beta-blockers and renin-angiotensin system inhibitors in acute myocardial infarction managed with inhospital coronary revascularization.

Sci Rep 2020 09 16;10(1):15184. Epub 2020 Sep 16.

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

Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70-0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55-0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66-0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68-0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57-0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40-0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48-0.86). This were consistent for left ventricular ejection fraction < 50% or ≥ 50%. In conclusion, in AMI managed with revascularization, both BB and ACEI/ARB were associated with a lower incidence of 12-month all-cause mortality. Combined BB and ACEI/ARB was associated with the lowest incidence of all-cause mortality and HF hospitalization.
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http://dx.doi.org/10.1038/s41598-020-72232-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495427PMC
September 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

Sleep apnoea and cardiovascular outcomes after coronary artery bypass grafting.

Heart 2020 10 18;106(19):1495-1502. Epub 2020 May 18.

Department of Cardiology, National University Heart Centre, Singapore.

Objective: Patients with advanced coronary artery disease are referred for coronary artery bypass grafting (CABG) and it remains unknown if sleep apnoea is a risk marker. We evaluated the association between sleep apnoea and major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing non-emergent CABG.

Methods: This was a prospective cohort study conducted between November 2013 and December 2018. Patients from four public hospitals referred to a tertiary cardiac centre for non-emergent CABG were recruited for an overnight sleep study using a wrist-worn Watch-PAT 200 device prior to CABG.

Results: Among the 1007 patients who completed the study, sleep apnoea (defined as apnoea-hypopnoea index ≥15 events per hour) was diagnosed in 513 patients (50.9%). Over a mean follow-up period of 2.1 years, 124 patients experienced the four-component MACCE (2-year cumulative incidence estimate, 11.3%). There was a total of 33 cardiac deaths (2.5%), 42 non-fatal myocardial infarctions (3.7%), 50 non-fatal strokes (4.9%) and 36 unplanned revascularisations (3.2%). The crude incidence of MACCE was higher in the sleep apnoea group than the non-sleep apnoea group (2-year estimate, 14.7% vs 7.8%; p=0.002). Sleep apnoea predicted the incidence of MACCE in unadjusted Cox regression analysis (HR 1.69; 95% CI 1.18 to 2.43), and remained statistically significant (adjusted HR 1.57; 95% CI 1.09 to 2.25), after adjustment for age, sex, body mass index, left ventricular ejection fraction, diabetes mellitus, hypertension, chronic kidney disease and excessive daytime sleepiness.

Conclusion: Sleep apnoea is independently associated with increased MACCE in patients undergoing CABG.

Trial Registration Number: NCT02701504.
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http://dx.doi.org/10.1136/heartjnl-2019-316118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509387PMC
October 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

Treating Very Long Coronary Artery Lesions in the Contemporary Drug-Eluting-Stent Era: Single Long 48 mm Stent Versus Two Overlapping Stents Showed Comparable Clinical Outcomes.

Cardiovasc Revasc Med 2020 09 13;21(9):1115-1118. Epub 2020 Feb 13.

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

Background/purpose: Percutaneous coronary intervention (PCI) of diffuse coronary artery disease (CAD) is associated with higher adverse clinical events. This study aimed to compare the clinical outcomes of patients treated with single long 48 mm contemporary drug eluting stents (SL-DES) versus two overlapping contemporary drug eluting stents (OL-DES) for very-long CAD.

Methods/materials: We analyzed the clinical outcome of 117 patients with SL-DES and 101 patients with OL-DES who underwent PCI between 1st July 2013 to 31st December 2016. The primary endpoint was target lesion failure (TLF) at two years, defined as a composite of cardiac mortality, target vessel myocardial infarction and target lesion revascularization.

Results: Mean age was 60.8 ± 10.5 years for SL-DES group and 60.5 ± 11.9 years in the OL-DES group. SL-DES has longer mean lesion length as compared to OL-DES (43.1 ± 3.7 mm vs. 41.83 ± 2.3 mm p = 0.003). There was no difference in TLF at two years between SL-DES and OL-DES (5.3% vs. 6.4%, adjusted odds ratio 1.43, 95% CI 0.50-4.11). There was one case of probable ST in each group. Contrast volume usage was lower for SL-DES than OL-DES in patients who underwent single vessel PCI.

Conclusions: Treatment of very-long CAD showed comparable TLF at two years for SL-DES versus OL-DES. Our results suggest that both strategies are reasonable treatment options for patients with diffuse CAD.
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http://dx.doi.org/10.1016/j.carrev.2020.02.005DOI Listing
September 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

Clinical and echocardiographic features of paradoxical low-flow and normal-flow severe aortic stenosis patients with concomitant mitral regurgitation.

Int J Cardiovasc Imaging 2020 Mar 27;36(3):441-446. Epub 2019 Nov 27.

Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Mitral regurgitation (MR) coexists in a significant proportion of patients with severe aortic stenosis (AS), and portends inferior therapeutic outcomes. In severe AS, MR is thought to contribute to a low-flow state by decreasing forward stroke volume. We investigated concomitant MR on the clinical and echocardiographic features of patients with "paradoxical" low-flow (PLF) and normal-flow (NF) severe AS. Clinical and echocardiographic profiles of 886 consecutive patients with index echocardiographic diagnosis of severe AS (AVA < 1.0 cm) were analysed retrospectively. All patients had preserved ejection fraction (LVEF  ≥ 50%, n = 645), and were divided into PLF (stroke volume index, SVI < 35 mL/m) and NF AS. They were then further subdivided based on the presence or absence of moderate-or-severe MR (msMR). A higher prevalence of concomitant msMR was observed in patients with PLF AS (14.9%; n = 33/221) compared to those with NF AS (8.0%; n = 34/424). Concomitant msMR was associated with echocardiographic features of increased diastolic dysfunction in both PLF AS and NF AS patients, as evidenced by increased LA diameter (PLF AS 52.9 ± 12.5 to 43.9 ± 8.9 mm; NF AS 29.6 ± 10.8 to 42.4 ± 8.8 mm; p < 0.001) and increased transmitral E/A ratio (PLF AS 1.26 ± 0.56 to 0.92 ± 0.43; NF AS 1.19 ± 0.63 to 0.94 ± 0.45; p = 0.004). Amongst patients with NF AS, msMR was additionally associated with increased E:e' ratio (25.5 ± 15.1 vs 19.3 ± 10.8; p = 0.025). Concomitant MR was more common in PLF AS compared to NF. Although possibly related to the MR, patients severe AS and MR appeared to have more severe diastolic dysfunction. Further studies are warranted to evaluate prognosis and guide management.
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http://dx.doi.org/10.1007/s10554-019-01735-1DOI Listing
March 2020

Rotational Atherectomy for Underexpanded Undilatable Stents: Is Ablating Away Stent Regret the Best Option?

Cardiovasc Revasc Med 2019 11 7;20(11):939-940. Epub 2019 Sep 7.

Department of Cardiology, National University Heart Centre, Singapore.

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http://dx.doi.org/10.1016/j.carrev.2019.09.005DOI Listing
November 2019

An Asian Perspective on Gender Differences in Clinical Outcomes and Echocardiographic Profiles of Patients With Medically Managed Severe Aortic Stenosis.

Heart Lung Circ 2021 Jan 23;30(1):115-120. Epub 2019 Jul 23.

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: Gender differences in valvular heart disease are increasingly recognised. A prior study has suggested better surgical outcomes in women with symptomatic aortic stenosis (AS). We investigate gender differences in medically managed severe AS.

Method: We studied 347 patients with severe AS (aortic valve area index <0.6 cm/m) in terms of baseline clinical background, echocardiographic characteristics, and clinical outcomes. Appropriate univariate and multivariate models were employed, while Kaplan-Meier curves were constructed to compare mortality outcomes.

Results: In total, 205 (59%) patients were women. Despite higher incidences of hypertension (75.6% vs 47.3%) and diabetes mellitus (46.5% vs 29.5%) in women, women had improved survival (Kaplan-Meier log-rank = 6.24, p = 0.012). After adjusting for age (hazard ratio [HR], 1.034; 95% confidence interval [CI], 1.014-1.054), hypertension (HR, 1.469; 95% CI, 0.807-2.673), diabetes (HR, 1.219; 95% CI, 0.693-2.145), and indexed aortic valve area (HR 0.145, 95% CI 0.031-0.684) on multivariate analyses, female gender remained independently associated with lower mortality (HR, 0.561; 95%, CI 0.332-0.947). Women tended to have smaller body surface area (BSA), left ventricular (LV) internal diastolic diameter, and smaller LV outflow tract diameter but were similar to men in terms of LV ejection fraction, AS severity, and patterns of LV remodelling.

Conclusions: Women appeared to have better outcomes compared to men in medically managed severe AS. These gender differences warrant further study and may affect prognosis, follow-up, and timing of valve surgery.
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http://dx.doi.org/10.1016/j.hlc.2019.06.725DOI Listing
January 2021

Sirolimus nanoparticles: (Delivering) a new hope in stentless percutaneous coronary intervention?

Cardiovasc Revasc Med 2019 03 6;20(3):179-180. Epub 2019 Jan 6.

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

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http://dx.doi.org/10.1016/j.carrev.2019.01.004DOI Listing
March 2019

Clinical Outcomes One Year and Beyond After Combination Sirolimus-Eluting Endothelial Progenitor Cell Capture Stenting During Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction.

Cardiovasc Revasc Med 2019 09 7;20(9):739-743. Epub 2018 Nov 7.

Department of Cardiology, National University Heart Center, Singapore, 1E Kent Ridge Road, NUHS Tower Block, Level 9, 119228, Singapore. Electronic address:

Background/purpose: Primary percutaneous coronary intervention (PCI) during acute ST-segment elevation myocardial infarction (STEMI) represents a thrombotic milieu and is associated with delayed healing after stenting. The pro-healing combination sirolimus eluting endothelial progenitor cell (EPC) capture stents encourage early endothelialization after stenting and may be beneficial in the STEMI population. We aim to evaluate the clinical outcomes one year and beyond for patients with STEMI who received the combination sirolimus eluting EPC capture stents during primary PCI.

Methods/material: All STEMI patients implanted with combination sirolimus eluting EPC capture stents during primary PCI from November 2013 to December 2016 were enrolled. The primary outcome was target lesion failure (TLF) at in-hospital, one-month, one-year and beyond one year.

Results: A total of 260 consecutive STEMI patients (283 lesions) were implanted with 313 combination sirolimus eluting EPC capture stents during primary PCI. Mean age was 56.1 ± 11.2 years and 88.8% were male. One in ten patients (10.9%) had cardiogenic shock on presentation, 7.3% needed mechanical ventilation and 7.7% had intra-aortic balloon pump inserted. A total of 97.9% of lesions achieve final TIMI 3 flow. Device success was seen in all patients. At extended follow up period (median 23.4 months), the clinical outcomes were TLF 8.8%, major adverse cardiovascular events 10.8%, cardiac mortality 4.2%, target vessel myocardial infarction 3.4%, target lesion revascularization 3.8%, and definite stent thrombosis 1.9%.

Conclusions: This study demonstrated acceptable clinical outcomes for an all-comers STEMI patients undergoing primary PCI with the use of combination sirolimus eluting EPC cell capture stents.
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http://dx.doi.org/10.1016/j.carrev.2018.11.004DOI Listing
September 2019

Treatment of Very Small De Novo Coronary Artery Disease With 2.0 mm Drug-Coated Balloons Showed 1-Year Clinical Outcome Comparable With 2.0 mm Drug-Eluting Stents.

J Invasive Cardiol 2018 07 15;30(7):256-261. Epub 2018 Apr 15.

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

Objective: To evaluate the 1-year clinical outcomes of patients treated with 2.0 mm drug-coated balloon (DCB) vs 2.0 mm drug-eluting stent (DES) implantation in small-caliber vessel de novo coronary artery disease (CAD).

Methods: All patients treated with 2.0 mm DCB or 2.0 mm DES for very small vessel de novo CAD from July 2014 to June 2016 were included in this study. The primary endpoint was the occurrence of target-lesion failure (TLF) and time to TLF, defined as a combination of cardiac mortality, target-vessel myocardial infarction, and target-lesion revascularization (TLR).

Results: A total of 87 patients (96 lesions) were implanted with 2.0 mm DCBs and 200 patients (223 lesions) were implanted with 2.0 mm DESs during the study period. Mean reference vessel diameter was similar between the DCB and DES groups (1.88 ± 0.38 mm vs 1.95 ± 0.21 mm, respectively; P=.11). The 1-year TLF rates were 7.0% in the DCB group and 8.2% in the DES group (P=.73). TLF was driven by TLR in both groups. Bailout stenting was performed in 7 patients (8 lesions) who received a DCB. Stent thrombosis was seen in 4 patients (2.0%) who underwent DES implantation. There was no vessel thrombosis noted in the DCB group. Cardiogenic shock was identified as a direct and significant predictor for both the occurrence of TLF and time to TLF.

Conclusions: In this first report, treatment of very small vessel CAD with 2.0 mm DCB vs 2.0 mm DES was associated with similar 1-year TLF rates.
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July 2018

Predicting changes in flow category in patients with severe aortic stenosis and preserved left ventricular ejection fraction on medical therapy.

Echocardiography 2017 Nov 13;34(11):1568-1574. Epub 2017 Sep 13.

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

Background/objectives: Controversy surrounds the prognosis and management of patients with paradoxical low-flow severe aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF). It was not certain if patients in a particular flow category remained in the same category as disease progressed. We investigated whether there were switches in categories and if so, their predictors.

Methods: Consecutive subjects (n = 203) with isolated severe AS and paired echocardiography (>180 days apart) were studied. They were divided into 4 groups, based on their flow categories and if they progressed on subsequent echocardiography to switch or remain in the same flow category. Univariate analyses of clinical and echocardiographic parameters identified predictors of these changes in flow category.

Results: One hundred eighteen were normal flow (SVI ≥ 35 mL/m ), while 85 were low flow on index echocardiography. In the patients with normal flow, 33% switched to low flow. This was associated with higher valvuloarterial impedance (Zva, P < .001) and lower systemic arterial compliance (SAC, P < .001) compared to index echocardiography, and predicted by higher initial Zva (optimized cutoff >4.77 mm Hg/mL/m , AUC = 0.81 [95% CI:0.75-0.87, P < .001]). In patients with low flow, 25% switched to normal flow, which was associated with lower Zva and higher SAC and the switch was predicted by a higher initial mean transaortic pressure gradient.

Conclusions: A significant number of patients switched flow categories in severe AS with preserved LVEF on subsequent echocardiography. Changes in flow were reflected by respective changes in Zva and SAC. Identifying echocardiographic predictors of a switch in category may guide prognostication and management of such patients.
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http://dx.doi.org/10.1111/echo.13676DOI Listing
November 2017
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