Publications by authors named "Chi-Hang Lee"

183 Publications

One-year outcomes of patients with ST-segment elevation myocardial infarction during the COVID-19 pandemic.

J Thromb Thrombolysis 2021 Aug 26. Epub 2021 Aug 26.

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

The pandemic has led to adverse short-term outcomes for patients with ST-segment elevation myocardial infarction (STEMI). It is unknown if this translates to poorer long-term outcomes. In Singapore, the escalation of the outbreak response on February 7, 2020 demanded adaptation of STEMI care to stringent infection control measures. A total of 321 patients presenting with STEMI and undergoing primary percutaneous coronary intervention at a tertiary hospital were enrolled and followed up over 1-year. They were allocated into three groups based on admission date-(1) Before outbreak response (BOR): December 1, 2019-February 6, 2020, (2) During outbreak response (DOR): February 7-March 31, 2020, and (3) control group: November 1-December 31, 2018. The incidence of cardiac-related mortality, cardiac-related readmissions, and recurrent coronary events were examined. Although in-hospital outcomes were worse in BOR and DOR groups compared to the control group, there were no differences in the 1-year cardiac-related mortality (BOR 8.7%, DOR 7.1%, control 4.8%, p = 0.563), cardiac-related readmissions (BOR 15.1%, DOR 11.6%, control 12.0%, p = 0.693), and recurrent coronary events (BOR 3.2%, DOR 1.8%, control 1.2%, p = 0.596). There were higher rates of additional PCI during the index admission in DOR, compared to BOR and control groups (p = 0.027). While patients admitted for STEMI during the pandemic may have poorer in-hospital outcomes, their long-term outcomes remain comparable to the pre-pandemic era.
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http://dx.doi.org/10.1007/s11239-021-02557-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390088PMC
August 2021

Comparison of Outcomes of Asymptomatic Moderate Aortic Stenosis With Preserved Left Ventricular Ejection Fraction in Patients ≥80 Years Versus 70-79 Years Versus <70 Years.

Am J Cardiol 2021 Oct 7;157:93-100. Epub 2021 Aug 7.

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:

Aortic stenosis (AS) is increasingly diagnosed in the aging population with more studies focused on the prognostic outcomes of severe asymptomatic AS. However, little is known about the outcomes of moderate asymptomatic AS in the elderly population. From 2001 to 2020, 738 consecutive patients with asymptomatic moderate AS with preserved left ventricular ejection fraction were studied. They were allocated according to the age group at the index echocardiography: very elderly (≥80 years), elderly (70 to 79 years) and control group (<70 years). The primary study outcomes were aortic valve replacement (AVR), congestive cardiac failure (CCF) and all-cause mortality. Overall, about one-third of the subjects were in the very elderly, elderly and control groups each. The median follow-up duration was 114.2 (interquartile range, 27.0 to 183.7) months. There was significantly higher all-cause mortality in the very elderly group (47.9%) followed by elderly (34.8%) and control group (21.9%). Similarly, there was significantly higher CCF rates in the very elderly group (5.8%) compared to elderly (5.1%) and control group (2.8%). There were significantly lower rates of AVR offered and completed in the very elderly group compared to control group. Multivariable logistic regression demonstrated that age ≥80 years remained an independent predictor of mortality after adjusting for important prognostic cofounders (Adjusted HR 2.424, 95% CI 1.728 to 3.400, p < 0.001). Cox regression showed no significant difference in mortality between patients ≥80 years with moderate AS compared to a younger age-group ≥70 years with severe AS. In conclusion, very elderly patients of ≥80 years of age with moderate AS have worse prognostic outcomes than their younger counterparts. They share similar unfavorable prognostic outcomes as those of a younger age-group ≥70 years with severe AS. Closer surveillance are warranted in this group of at-risk elderly patients.
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http://dx.doi.org/10.1016/j.amjcard.2021.07.015DOI Listing
October 2021

Sleep apnea and recurrent heart failure hospitalizations after coronary artery bypass grafting.

J Clin Sleep Med 2021 Jun 21. Epub 2021 Jun 21.

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

Study Objectives: Sleep apnea is prevalent in patients undergoing coronary artery bypass grafting (CABG). We investigated the relationship between sleep apnea and recurrent heart failure hospitalizations in patient undergoing non-urgent CABG.

Methods: Between November 2013 and December 2018, 1007 patients completed a sleep study prior to CABG and were followed up until April 2020. Recurrent heart failure hospitalizations were analyzed by Poisson, negative binomial, Andersen-Gill, and joint frailty models, with partial and full adjustment for covariates.

Results: At an average follow-up of 3.3 years, the number of patients with 0, 1, or ≥2 heart failure hospitalizations were 908 (90.2%), 62 (6.2%), and 37 (3.7%), respectively. The total number of heart failure hospitalizations was 179, comprising 62 (35%) first and 117 (65%) repeat events. The numbers of heart failure hospitalizations for the sleep apnea (n = 513, 50.9%) and non-sleep apnea groups were 127 and 52, respectively. Negative binomial regression demonstrated that sleep apnea was associated with recurrent heart failure hospitalizations (fully adjusted rate ratio, 1.71; 95% confidence interval [CI], 1.12-2.62; p = 0.013). Similar results were found in Poisson (1.63; 95%CI, 1.15-2.31; p = 0.006), Andersen-Gill (1.66; 95% CI, 1.01-2.75; p = 0.047), and joint frailty models (1.72; 95% CI, 1.00-3.01; p = 0.056).

Conclusions: In patients after CABG, repeat events accounted for two-thirds of heart failure hospitalizations. Sleep apnea was independently associated with recurrent heart failure hospitalizations.
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http://dx.doi.org/10.5664/jcsm.9442DOI Listing
June 2021

Obstructive sleep apnea, sleep duration and chronic kidney disease in patients with coronary artery disease.

Sleep Med 2021 08 31;84:268-274. Epub 2021 May 31.

Unidade de Hipertensão, Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil; Unidade de Hipertensão, Disciplina de Nefrologia, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil. Electronic address:

Background: Limited evidence is available addressing the potential role of sleep disorders on renal function. Here, we aimed to explore the associations of obstructive sleep apnea (OSA) and sleep duration (SD) with renal function in subjects with high cardiovascular risk.

Methods: Consecutive subjects with coronary artery disease (CAD) underwent clinical evaluation, sleep study to define OSA and one-week wrist actigraphy to objectively measure SD. OSA was defined by an apnea-hypopnea index (AHI) of ≥15 events/hour. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation. We analyzed the associations of OSA and SD with continuous eGFR values and according to the presence of CKD (eGFR<60 mL/min/1.73 m) after adjusting for multiple confounding factors.

Results: We studied 242 subjects (62.8% men). The frequency of OSA was 55.4% and the median SD was 412.8 (363.4-457.25) min. There was no difference in the eGFRs between participants with and without OSA (69.3 ± 19.1 vs. 74.6 ± 19.3 mL/min/1.73 m, p = 0.72) and the rate of eGFR <60 mL/min/1.73 m (34.3% vs. 25.9%; p = 0.21). Similarly, we did not find differences in patients in eGFR for those with SD ≥ 6 h versus SD < 6 h (72.5 ± 20.3 vs. 71.4 ± 19.1 mL/min/1.73 m, p = 0.72). In the linear regression analysis, AHI was independently associated with an eGFR<60 mL/min/1.73 m in the unadjusted model [-0.15 (-0.27 to -0.04)], (P = 0.01), but not in the adjusted models. Analyses of continuous SD or the stratification in SD ≥ 6 h or <6 h also revealed neutral results on eGFR.

Conclusion: OSA severity and SD were not independently associated with CKD in subjects with CAD.
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http://dx.doi.org/10.1016/j.sleep.2021.05.025DOI Listing
August 2021

Effects of Colchicine on Cardiovascular Outcomes in Patients with Coronary Artery Disease: A Systematic Review and One-Stage and Two-Stage Meta-Analysis of Randomized-Controlled Trials.

High Blood Press Cardiovasc Prev 2021 Jul 18;28(4):343-354. Epub 2021 May 18.

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

Aim: Colchicine has received emerging interest due to its cardiovascular benefits in patients with coronary artery disease (CAD). We conducted a one-stage meta-analysis of reconstructed individual patient data (IPD) from randomized-controlled trials to summarize the effects of colchicine on cardiovascular outcomes in patients with CAD.

Methods: Four databases (PubMed, Embase, Cochrane, SCOPUS) were searched for articles published from inception to 30th September 2020, examining the effect of colchicine on cardiovascular outcomes in patients with CAD, yielding 10 randomized-controlled trials with a combined cohort of 12,781 patients. IPD was reconstructed from Kaplan-Meier curves published in 3 studies and analysed using the shared-frailty Cox model. Aggregate data meta-analysis of all 10 studies was performed for outcomes unsuitable for IPD reconstruction.

Results: In patients receiving colchicine compared to placebo, one-stage meta-analysis demonstrated a hazard ratio of 0.70 (95% CI 0.61-0.80) for the composite outcome of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent hospitalization for angina requiring coronary revascularization. Aggregate data meta-analysis demonstrated a significant reduction in hazard rate for stroke (HR 0.45; 95% CI 0.27-0.75) and urgent revascularization (HR 0.59; 95% CI 0.38-0.91); and a relative risk reduction for myocardial infarction (RR 0.72; 95% CI of 0.52-1.00) and post-operative atrial fibrillation (RR 0.64; 95% CI 0.48-0.86).

Conclusion: Given the significant benefits of colchicine demonstrated on IPD, and its consistent benefits when analyzed using aggregate data meta-analysis, we propose that colchicine may be considered as an additional pharmacological adjunct to the first line therapy for patients with coronary artery disease.
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http://dx.doi.org/10.1007/s40292-021-00460-yDOI Listing
July 2021

Outcomes of a multi-ethnic Asian population on combined treatment with clopidogrel and omeprazole in 12,440 patients.

J Thromb Thrombolysis 2021 May 6. Epub 2021 May 6.

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

Omeprazole is commonly co-prescribed with clopidogrel. Clopidogrel requires bio-activation by cytochrome P450 CYP2C19. Omeprazole may reduce clopidogrel's antithrombotic efficacy by inhibiting CYP2C19. Studies in Caucasians receiving omeprazole with clopidogrel showed no significant increase in death and myocardial infarction with this drug-drug interaction. There are limited large-scale studies in Asians, who may have a greater prevalence of CYP2C19 loss-of-function polymorphisms. A single centre retrospective cohort study was undertaken based on a review of medication records and prescription data. Patients prescribed clopidogrel from 2009 to 2012 were followed-up with until December 2012 (median:29 months). The primary outcome was all-cause mortality and secondary outcomes were myocardial infarction (MI), cerebrovascular accidents, and subsequent coronary interventions. Of 12,440 patients prescribed clopidogrel, 62%(n = 7714) were on omeprazole (63.8% Chinese, 13.9% Malay, 12.4% Indian, 10.0% others), and 38%(n = 4726) were not on omeprazole or other proton pump inhibitors (62.6% Chinese, 13.5% Malay, 10.7% Indian, 13.2% others). Mortality after co-prescription occurred in 14.3%(n = 1101) of patients, compared to 6.3%(n = 300) of patients prescribed clopidogrel only. Multivariate analysis using propensity score adjusted analysis showed no significant increase in all-cause mortality with co-prescription (adjusted hazards ratio [AHR] 1.13, [95%CI 0.95-1.35]). Patients on co-prescription had a higher risk of subsequent MI (16% vs 3.8%; AHR 2.03 [95%CI 1.70-2.44]), but not of cerebrovascular accidents (5.0% vs 2.0%; AHR 0.98 [95%CI 0.76-1.27]) or coronary interventions (1.7% vs 0.7%; AHR 1.28 [95%CI 0.83-1.96]). The risk of a subsequent MI was higher in the Malay (AHR 2.43 [95%CI 1.68-3.52]) and Chinese (AHR 2.06 [95%CI 1.63-2.60]) population as compared to the Indian (AHR 1.56 [95%CI 1.06-2.31]) population. In conclusion, the use of clopidogrel with omeprazole is associated with an increased risk of MI, but not mortality or stroke, in this multi-ethnic Asian population. These risks appear to vary among different ethnic groups.
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http://dx.doi.org/10.1007/s11239-021-02472-wDOI Listing
May 2021

Comparing the clinical outcomes across different sodium/glucose cotransporter 2 (SGLT2) inhibitors in heart failure patients: a systematic review and network meta-analysis of randomized controlled trials.

Eur J Clin Pharmacol 2021 Oct 3;77(10):1453-1464. Epub 2021 May 3.

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

Purpose: Empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin have been shown in randomized controlled trials to improve cardiovascular, metabolic, and renal outcomes in heart failure patients. To date, there has not been any meta-analysis examining the differences in clinical outcomes across different SGLT2 inhibitors in heart failure patients.

Methods: Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched on 13 September 2020 for articles published from 1 January 2000 to 13 September 2020 examining the effect of SGLT2 inhibitors on cardiovascular, renal, and metabolic outcomes in heart failure patients. Frequentist network meta-analysis was performed on extracted data.

Results: Ten randomized controlled trials were included with a combined cohort of 15,373 patients. In heart failure patients, frequentist network meta-analysis demonstrated no demonstrable difference in treatment effect across the SGLT2 inhibitors for heart failure hospitalization, cardiovascular deaths, composite of cardiovascular deaths and heart failure hospitalizations, all-cause mortality, and a composite of cardiovascular deaths and non-fatal myocardial infarction and non-fatal stroke. There was no demonstrable difference in treatment effect for worsening renal function or the weighted mean difference for weight, hemoglobin A1c, and systolic blood pressure.

Conclusions: There were no demonstrable treatment differences across SGLT2 inhibitors across cardiovascular, renal, and metabolic outcomes, although this needs to be interpreted considering the wide confidence intervals, limited number of included studies, and heterogeneity present. Future research of different SGLT2 inhibitors in head-to-head studies is warranted to determine if there is a drug class effect.
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http://dx.doi.org/10.1007/s00228-021-03147-4DOI Listing
October 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

The Global Effect of the COVID-19 Pandemic on STEMI Care: A Systematic Review and Meta-analysis.

Can J Cardiol 2021 Apr 20. Epub 2021 Apr 20.

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

Background: The COVID-19 pandemic has affected patients with ST-segment elevation myocardial infarction (STEMI) requiring primary percutaneous coronary intervention (PCI) worldwide. In this review we examine the global effect of the COVID-19 pandemic on incidence of STEMI admissions, and relationship between the pandemic and door to balloon time (D2B), all-cause mortality, and other secondary STEMI outcomes.

Methods: We performed a systematic review and meta-analysis to primarily compare D2B time and in-hospital mortality of STEMI patients who underwent primary PCI during and before the pandemic. Subgroup analyses were performed to investigate the influence of geographical region and income status of a country on STEMI care. An online database search included studies that compared the aforementioned outcomes of STEMI patients during and before the pandemic.

Results: In total, 32 articles were analyzed. Overall, 19,140 and 68,662 STEMI patients underwent primary PCI during and before the pandemic, respectively. Significant delay in D2B was observed during the pandemic (weighted mean difference, 8.10 minutes; 95% confidence interval [CI], 3.90-12.30 minutes; P = 0.0002; I = 90%). In-hospital mortality was higher during the pandemic (odds ratio [OR], 1.27; 95% CI, 1.09-1.49; P = 0.002; I = 36%), however this varied with factors such as geographical location and income status of a country. Subgroup analysis showed that low-middle-income countries observed a higher rate of mortality during the pandemic (OR, 1.52; 95% CI, 1.13-2.05; P = 0.006), with a similar but insignificant trend seen among the high income countries (OR, 1.17; 95% CI, 0.95-1.44; P = 0.13).

Conclusions: The COVID-19 pandemic is associated with worse STEMI performance metrics and clinical outcome, particularly in the Eastern low-middle-income status countries. Better strategies are needed to address these global trends in STEMI care during the pandemic.
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http://dx.doi.org/10.1016/j.cjca.2021.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056787PMC
April 2021

Reply to letter to the editor obstructive sleep apnea and cardiac biomarkers in patients with acute coronary syndrome.

Sleep Med 2021 05 27;81:245. Epub 2021 Feb 27.

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

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http://dx.doi.org/10.1016/j.sleep.2021.02.046DOI Listing
May 2021

Obstructive sleep apnea and atrial fibrillation: we need to go step by step.

J Clin Sleep Med 2021 05;17(5):869-870

Group of Precision Medicine in Chronic Diseases, Hospital Arnau de Vilanova and Santa Maria, IRBLleida, Lleida, Spain.

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http://dx.doi.org/10.5664/jcsm.9242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8320472PMC
May 2021

Effects of Sodium/Glucose Cotransporter 2 (SGLT2) Inhibitors on Cardiovascular and Metabolic Outcomes in Patients Without Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized-Controlled Trials.

J Am Heart Assoc 2021 02 24;10(5):e019463. Epub 2021 Feb 24.

Department of Medicine Yong Loo Lin School of MedicineNational University of Singapore Singapore.

Background Recent studies have increasingly shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors may have beneficial cardiovascular and metabolic effects in patients without diabetes mellitus. Hence, we conducted a systematic review and meta-analysis to determine the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. Methods and Results Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on August 30, 2020 for articles published from January 1, 2000 to August 30, 2020, for studies that examined the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. A random-effects pairwise meta-analysis model was used to summarize the studies. A total of 8 randomized-controlled trials were included with a combined cohort of 5233 patients. In patients without diabetes mellitus, those with heart failure treated with SGLT2 inhibitors had a 20% relative risk reduction in cardiovascular deaths and heart failure hospitalizations, compared with those who were not treated (risk ratio, 0.78; <0.001). We additionally found that treatment with SGLT2 inhibitors improved multiple metabolic indices. Patients on SGLT2 inhibitors had a reduction in body weight of -1.21 kg (<0.001), body mass index of -0.47 kg/m (<0.001), systolic blood pressure of -1.90 mm Hg (=0.04), and fasting plasma glucose of -0.38 mmol/L (=0.05), compared with those without. There were no between-group differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, waist circumference, diastolic blood pressure, glycated hemoglobin, low-density lipoprotein cholesterol levels, and estimated glomerular filtration rates. Across our combined cohort of 5233 patients, hypoglycemia was reported in 22 patients. Conclusions SGLT2 inhibitors improve cardiovascular outcomes in patients without diabetes mellitus with heart failure. In patients without diabetes mellitus, SGLT2 inhibitors showed positive metabolic outcomes in weight and blood pressure control.
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http://dx.doi.org/10.1161/JAHA.120.019463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174267PMC
February 2021

Obstructive sleep apnea during acute coronary syndrome is related to myocardial necrosis and wall stress.

Sleep Med 2021 03 6;79:79-82. Epub 2021 Jan 6.

Department of Cardiology, National University Heart Centre, Singapore, Singapore; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cardiovascular Research Institute, National University of Singapore, Singapore. Electronic address:

Background: The relative contribution of pathophysiological mechanisms in acute coronary syndrome (ACS) towards obstructive sleep apnea (OSA) is not well-studied. We examined the correlation between severity of OSA and inflammation, myocardial necrosis, wall stress, and fibrosis.

Methods: A total of 89 patients admitted with ACS underwent a sleep study during index admission. Plasma levels of high-sensitivity C-reactive protein (hs-CRP), troponin I, N-terminal pro-brain natriuretic peptide (NT-proBNP), and suppression of tumorigenicity 2 (ST2) were prospectively analyzed. Two patients diagnosed with central sleep apnea were excluded.

Results: The recruited patients were divided into no (AHI <5 events/hour, 9.2%), mild (5-<15, 27.6%), moderate (15-<30, 21.8%), and severe (≥30, 41.4%) OSA. Compared to the no, mild and moderate OSA groups, the severe OSA group had a higher body mass index (p = 0.005). They were also more likely to present with ST-segment elevation ACS (versus non-ST-segment elevation ACS) (p = 0.041), have undergone previous coronary artery bypass grafting (p = 0.013), demonstrate complete coronary occlusion during baseline coronary angiography (p = 0.049), and have a larger left atrial diameter measured on echocardiography (p = 0.029). Likewise, the severe OSA group had higher plasma levels of hs-CRP (p = 0.004), troponin I (p = 0.017), and NT-proBNP (p = 0.004), but not ST2 (p = 0.10). After adjustment for the effects of confounding variables, OSA was independently associated with troponin I (ie, myocardial necrosis; p = 0.001) and NT-proBNP (ie, myocardial wall stress; p = 0.008).

Conclusion: Severe OSA during the acute phase of ACS was associated with extensive myocardial necrosis and high myocardial wall stress, but not with inflammation and myocardial fibrosis.
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http://dx.doi.org/10.1016/j.sleep.2021.01.006DOI Listing
March 2021

Chemotherapy and adverse cardiovascular events in colorectal cancer patients undergoing surgical resection.

World J Surg Oncol 2021 Jan 21;19(1):21. Epub 2021 Jan 21.

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

Background: Colorectal cancer patients undergoing surgical resection are at increased short-term risk of post-operative adverse events. However, specific predictors for long-term major adverse cardiac and cerebrovascular events (MACCE) are unclear. We hypothesised that patients who receive chemotherapy are at higher risk of MACCE than those who did not.

Methods: In this retrospective study, 412 patients who underwent surgical resection for newly diagnosed colorectal cancer from January 2013 to April 2015 were grouped according to chemotherapy status. MACCE was defined as a composite of cardiovascular death, myocardial infarction, stroke, unplanned revascularisation, hospitalisation for heart failure or angina. Predictors of MACCE were identified using competing risks regression, with non-cardiovascular death a competing risk.

Results: There were 200 patients in the chemotherapy group and 212 patients in the non-chemotherapy group. The overall prevalence of prior cardiovascular disease was 20.9%. Over a median follow-up duration of 5.1 years from diagnosis, the incidence of MACCE was 13.3%. Diabetes mellitus and prior cardiovascular disease were associated with an increased risk of MACCE (subdistribution hazard ratio, 2.56; 95% CI, 1.48-4.42) and 2.38 (95% CI, 1.36-4.18) respectively. The chemotherapy group was associated with a lower risk of MACCE (subdistribution hazard ratio, 0.37; 95% CI, 0.19-0.75) compared to the non-chemotherapy group.

Conclusions: Amongst colorectal cancer patients undergoing surgical resection, there was a high incidence of MACCE. Diabetes mellitus and prior cardiovascular disease were associated with an increased risk of MACCE. Chemotherapy was associated with a lower risk of MACCE, but further research is required to clarify this association.
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http://dx.doi.org/10.1186/s12957-021-02125-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819286PMC
January 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

Impact of the COVID-19 Pandemic on Door-to-Balloon Time for Primary Percutaneous Coronary Intervention - Results From the Singapore Western STEMI Network.

Circ J 2021 01 7;85(2):139-149. Epub 2020 Nov 7.

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

Background: Little is known about the effect of the coronavirus disease 2019 (COVID-19) pandemic and the outbreak response measures on door-to-balloon time (D2B). This study examined both D2B and clinical outcomes of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI).Methods and Results:This was a retrospective study of 303 STEMI patients who presented directly or were transferred to a tertiary hospital in Singapore for PPCI from October 2019 to March 2020. We compared the clinical outcomes of patients admitted before (BOR) and during (DOR) the COVID-19 outbreak response. The study outcomes were in-hospital death, D2B, cardiogenic shock and 30-day readmission. For direct presentations, fewer patients in the DOR group achieved D2B time <90 min compared with the BOR group (71.4% vs. 80.9%, P=0.042). This was more apparent after exclusion of non-system delay cases (DOR 81.6% vs. BOR 95.9%, P=0.006). Prevalence of both out-of-hospital cardiac arrest (9.5% vs. 1.9%, P=0.003) and acute mitral regurgitation (31.6% vs. 17.5%, P=0.006) was higher in the DOR group. Mortality was similar between groups. Multivariable regression showed that longer D2B time was an independent predictor of death (odds ratio 1.005, 95% confidence interval 1.000-1.011, P=0.029).

Conclusions: The COVID-19 pandemic and the outbreak response have had an adverse effect on PPCI service efficiency. The study reinforces the need to focus efforts on shortening D2B time, while maintaining infection control measures.
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http://dx.doi.org/10.1253/circj.CJ-20-0800DOI Listing
January 2021

The Emerging Role of Drug-Induced Sleep Endoscopy in the Management of Obstructive Sleep Apnea.

Clin Exp Otorhinolaryngol 2021 May 16;14(2):149-158. Epub 2020 Oct 16.

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

Obstructive sleep apnea is a prevalent sleep disorder characterized by partial or complete obstruction of the upper airway. Continuous positive airway pressure is the first-line therapy for most patients, but adherence is often poor. Alternative treatment options such as mandibular advancement devices, positional therapy, and surgical interventions including upper airway stimulation target different levels and patterns of obstruction with varying degrees of success. Drug-induced sleep endoscopy enables the visualization of upper airway obstruction under conditions mimicking sleep. In the era of precision medicine, this additional information may facilitate better decision-making when prescribing alternative treatment modalities, with the hope of achieving better adherence and/or success rates. This review discusses the current knowledge and evidence on the role of drug-induced sleep endoscopy in the non-positive airway pressure management of obstructive sleep apnea.
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http://dx.doi.org/10.21053/ceo.2020.01704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111386PMC
May 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

Prioritizing Candidates of Post-Myocardial Infarction Heart Failure Using Plasma Proteomics and Single-Cell Transcriptomics.

Circulation 2020 10 4;142(15):1408-1421. Epub 2020 Sep 4.

Department of Medicine, Yong Loo-Lin School of Medicine, National University of Singapore (M.Y.C., M.E., S.H.T., C.L.D., L.H.L., W.-M.S., J.P.L., C.-H.L., R.S.Y.F., M.A.A.-J., A.M.R.).

Background: Heart failure (HF) is the most common long-term complication of acute myocardial infarction (MI). Understanding plasma proteins associated with post-MI HF and their gene expression may identify new candidates for biomarker and drug target discovery.

Methods: We used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.9 years. We then correlated plasma proteins with left ventricular ejection fraction measured at 4 months post-MI and identified proteins potentially coregulated in post-MI HF using weighted gene co-expression network analysis. A Singapore cohort (IMMACULATE [Improving Outcomes in Myocardial Infarction through Reversal of Cardiac Remodelling]) of 223 patients post-MI, of which 33 patients were hospitalized for HF (median follow-up, 2.0 years), was used for further candidate enrichment of plasma proteins by using Fisher meta-analysis, resampling-based statistical testing, and machine learning. We then cross-referenced differentially expressed proteins with their differentially expressed genes from single-cell transcriptomes of nonmyocyte cardiac cells isolated from a murine MI model, and single-cell and single-nucleus transcriptomes of cardiac myocytes from murine HF models and human patients with HF.

Results: In the CDCS cohort, 212 differentially expressed plasma proteins were significantly associated with subsequent HF events. Of these, 96 correlated with left ventricular ejection fraction measured at 4 months post-MI. Weighted gene co-expression network analysis prioritized 63 of the 212 proteins that demonstrated significantly higher correlations among patients who developed post-MI HF in comparison with event-free controls (data set 1). Cross-cohort meta-analysis of the IMMACULATE cohort identified 36 plasma proteins associated with post-MI HF (data set 2), whereas single-cell transcriptomes identified 15 gene-protein candidates (data set 3). The majority of prioritized proteins were of matricellular origin. The 6 most highly enriched proteins that were common to all 3 data sets included well-established biomarkers of post-MI HF: N-terminal B-type natriuretic peptide and troponin T, and newly emergent biomarkers, angiopoietin-2, thrombospondin-2, latent transforming growth factor-β binding protein-4, and follistatin-related protein-3, as well.

Conclusions: Large-scale human plasma proteomics, cross-referenced to unbiased cardiac transcriptomics at single-cell resolution, prioritized protein candidates associated with post-MI HF for further mechanistic and clinical validation.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.045158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547904PMC
October 2020

Sleep Apnea and Heart.

Sleep Med Res 2019 Dec 31;10(2):67-74. Epub 2019 Dec 31.

Department of Cardiology, National University Heart Centre, Singapore.

Scientific investigations in the past few decades have supported the important role of sleep in various domains of health. Sleep apnea is a highly prevalent yet underdiagnosed sleep disorder representing a valid cardiovascular risk factor, particularly for hypertension. While several studies have demonstrated the benefits of sleep apnea treatment on subclinical cardiovascular measures, there is a paucity of studies proving reduction of cardiovascular events and mortality. Sufficient and high-quality sleep is also important in the maintenance of cardiovascular health. Future investigations should focus on improving identification of patients at greatest risk of adverse cardiovascular s sequalae of sleep apnea and testing the therapeutic benefit of sleep apnea treatment in this vulnerable group.
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http://dx.doi.org/10.17241/smr.2019.00493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7375706PMC
December 2019

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

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

Obstructive sleep apnea during rapid eye movement sleep in patients after percutaneous coronary intervention: a multicenter study.

Sleep Breath 2021 03 8;25(1):125-133. Epub 2020 Apr 8.

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

Purpose: Obstructive sleep apnea (OSA) during the rapid eye movement (REM) stage of the sleep cycle is associated with intense hypoxemia and cardiovascular instability. We characterized OSA during REM sleep in patients after percutaneous coronary intervention.

Methods: In this multicenter study, 204 patients who had undergone percutaneous coronary intervention in the prior 6 to 36 months were recruited for in-laboratory polysomnography. The primary measure was respiratory events during REM sleep. The patients were divided into 2 groups: (1) OSA during REM sleep (≥ 15 events/h) and (2) absence of OSA during REM sleep (< 15 events/h).

Results: Based on the overall apnea-hypopnea index ≥ 15, 148 patients (74.0%) had OSA. After excluding patients with failed polysomnography or REM sleep < 30 min, 163 patients formed the cohort for this analysis. OSA during REM sleep was diagnosed in 132 patients (81%). Compared with the patients without OSA during REM sleep, those with OSA during REM sleep had a higher body mass index (p = 0.003) and systolic blood pressure (p = 0.041), and a higher prevalence of diabetes mellitus (p = 0.029). Logistic regression analysis, including age, sex, diabetes mellitus, indication for percutaneous coronary intervention, and indication for multi-vessel percutaneous coronary intervention, showed that diabetes mellitus was the only independent predictor of OSA during REM sleep (odds ratio 2.83; 95% CI, 1.17 to 6.83; p = 0.021).

Conclusion: In patients treated with percutaneous coronary intervention, there was a high prevalence of OSA during REM sleep. Diabetes mellitus was an independent predictor of OSA during REM sleep.
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http://dx.doi.org/10.1007/s11325-020-02057-6DOI Listing
March 2021

The remodelling index risk stratifies patients with hypertensive left ventricular hypertrophy.

Eur Heart J Cardiovasc Imaging 2021 05;22(6):670-679

Department of Cardiology, National Heart Center Singapore, Singapore.

Aims: Hypertensive left ventricular hypertrophy (LVH) is associated with increased cardiovascular events. We previously developed the remodelling index (RI) that incorporated left ventricular (LV) volume and wall-thickness in a single measure of advanced hypertrophy in hypertensive patients. This study examined the prognostic potential of the RI in reference to contemporary LVH classifications.

Methods And Results: Cardiovascular magnetic resonance was performed in 400 asymptomatic hypertensive patients. The newly derived RI (EDV3t, where EDV is LV end-diastolic volume and t is the maximal wall thickness across 16 myocardial segments) stratified hypertensive patients: no LVH, LVH with normal RI (LVHNormal-RI), and LVH with low RI (LVHLow-RI). The primary outcome was a composite of all-cause mortality, acute coronary syndromes, strokes, and decompensated heart failure. LVHLow-RI was associated with increased LV mass index, fibrosis burden, impaired myocardial function and elevated biochemical markers of myocardial injury (high-sensitive cardiac troponin I), and wall stress. Over 18.3 ± 7.0 months (601.3 patient-years), 14 adverse events occurred (2.2 events/100 patient-years). Patients with LVHLow-RI had more than a five-fold increase in adverse events compared to those with LVHNormal-RI (11.6 events/100 patient-years vs. 2.0 events/100 patient-years, respectively; log-rank P < 0.001). The RI provided incremental prognostic value over and above a model consisting of clinical variables, LVH and concentricity; and predicted adverse events independent of clinical variables, LVH, and other prognostic markers. Concentric and eccentric LVH were associated with adverse prognosis (log-rank P = 0.62) that was similar to the natural history of hypertensive LVH (5.1 events/100 patient-years).

Conclusion: The RI provides prognostic value that improves risk stratification of hypertensive LVH.
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http://dx.doi.org/10.1093/ehjci/jeaa040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110315PMC
May 2021

Diabetes mellitus is associated with high sleep-time systolic blood pressure and non-dipping pattern.

Postgrad Med 2020 May 24;132(4):346-351. Epub 2020 Mar 24.

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

Introduction: Compared to clinic blood pressure (BP), sleep-time BP and non-dipping BP pattern are better predictors of target organ damage and cardiovascular sequalae.

Aim: In a retrospective study, we determined whether diabetes mellitus (DM) status is associated with high sleep-time BP and non-dipping pattern.

Methods: We analyzed 1092 patients who underwent ambulatory BP monitoring between 2015 and 2017 in a tertiary cardiology institution. During a 24-hour period, BP was automatically measured every 15 minutes between 7:00 AM and 11:59 PM and every 30 minutes thereafter.

Results: Compared with the non-DM group (n = 910), the DM group (n = 182) had a higher 24-hour systolic BP (137 ± 17 vs. non-DM, 132 ± 14 mmHg, p < 0.001) and sleep-time systolic BP (132 ± 20 vs. 123 ± 16 mmHg, p < 0.001), and was more likely to exhibit non-dipping (63% vs 42%, p˂0.001). The DM group was also less likely to meet the guideline-recommended target of 120/70 mmHg for the sleep-time BP measured via ambulatory monitoring (22% vs. 34%, p = 0.002). After adjusting for the effects of age, sex, body mass index, smoking, urea, eGFR, previous myocardial infarction, previous percutaneous coronary intervention, previous coronary artery bypass surgery, and previous stroke, DM remained a significant independent predictor of a higher 24-hour systolic BP (coefficient: 2.8, 95% confidence interval: 0.1-5.5, p = 0.042) and higher sleep-time systolic BP (coefficient: 4.2, 95% confidence interval: 1.1-7.3, p = 0.008). There was a trend toward more sleep-time non-dipping BP pattern (odds ratio: 1.4, 95% confidence interval: 1.0-2.0, p = 0.087) in the DM group.

Conclusion: DM is independently associated with suboptimal 24-hour BP control. This association is mainly attributed to a high sleep-time systolic BP.
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http://dx.doi.org/10.1080/00325481.2020.1745537DOI Listing
May 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

Patients with acute and chronic coronary syndromes have elevated long-term thrombin generation.

J Thromb Thrombolysis 2020 Aug;50(2):421-429

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

Coronary artery disease is a leading cause of morbidity and mortality worldwide. Despite significant advances in revascularization strategies and antiplatelet therapy with aspirin and/or P2Y receptor antagonist, patients with acute coronary syndrome (ACS) continue to be at long-term risk of further cardiovascular events. Besides platelet activation, the role of thrombin generation (TG) in atherothrombotic complications is widely recognized. In this study, we hypothesized that there is an elevation of coagulation activation persists beyond 12 months in patients with ACS and chronic coronary syndrome (CCS) when compared with healthy controls. We measured TG profiles of patients within 72 h after percutaneous coronary intervention, at 6-month, 12-month and 24-month. Our results demonstrated that TG of patients with ACS (n = 114) and CCS (n = 40) were persistently elevated when compared to healthy individuals (n = 50) in peak thrombin (ACS 273.1 nM vs CCS 287.3 nM vs healthy 234.3 nM) and velocity index (ACS 110.2 nM/min vs CCS 111.0 nM/min vs healthy 72.9 nM/min) at 24-month of follow-up. Our results suggest a rationale for addition of anticoagulation to antiplatelet therapy in preventing long-term ischemic events after ACS. Further research could clarify whether the use of TG parameters to enable risk stratification of patients at heightened long-term procoagulant risk who may benefit most from dual pathway inhibition.
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http://dx.doi.org/10.1007/s11239-020-02066-yDOI Listing
August 2020

Prevalence, Characteristics, and Association of Obstructive Sleep Apnea with Blood Pressure Control in Patients with Resistant Hypertension.

Ann Am Thorac Soc 2019 11;16(11):1414-1421

Hospital Universitari Arnau de Vilanova and Santa Maria, Group of Translational Research in Respiratory Medicine, Institute for Biomedical Research in Lleida Dr. Pifarré Foundation, Lleida, Catalunya, Spain.

Obstructive sleep apnea (OSA) is associated with poor blood pressure (BP) control and resistant hypertension (RH). Nevertheless, studies assessing its prevalence, characteristics, and association with BP control in patients with RH are limited. The aim of this multicenter study was to assess the prevalence of OSA in a large cohort of subjects with RH and to evaluate the association of OSA with BP control. We recruited consecutive subjects with RH from three countries. A formal sleep test and blood pressure measurements, including 24-hour ambulatory blood pressure monitoring, were performed in all participants. In total, 284 subjects with RH were included in the final analysis. Of these, 83.5% (95% confidence interval [CI], 78.7-87.3%) had OSA (apnea-hypopnea index ≥ 5 events/h); 31.7% (95% CI, 26.5-37.3%) had mild OSA, 25.7% (95% CI, 21-31.1%) had moderate OSA, and 26.1% (95% CI, 21.3-31.5%) had severe OSA. Patients with severe OSA had higher BP values than subjects with mild to moderate or no OSA. A greater effect was observed on the average nighttime BP, with an adjusted effect of 5.72 mm Hg (95% CI, 1.08-10.35 mm Hg) in severe OSA compared with participants without OSA. A dose-response association between the severity of OSA and BP values was observed. The prevalence of severe OSA was slightly higher in uncontrolled participants (adjusted odds ratio, 1.69; 95% CI, 0.97-2.99) but was not statistically significant. The present study confirms the high prevalence of OSA in participants with RH. Furthermore, it shows a dose-response association between OSA severity and BP measurements, especially in the nighttime.Clinical trial registered with www.clinicaltrials.gov (NCT03002558).
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http://dx.doi.org/10.1513/AnnalsATS.201901-053OCDOI Listing
November 2019

Screening and treatment of obstructive sleep apnea in acute coronary syndrome. A randomized clinical trial.

Int J Cardiol 2020 01 3;299:20-25. Epub 2019 Jul 3.

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

Background: We evaluated the effects of sleep-study guided multidisciplinary therapy (SGMT) of obstructive sleep apnoea (OSA) in patients presenting with acute coronary syndrome.

Methods: Eligible patients were randomized into (1) SGMT, comprised a sleep study during the index admission and continuous positive airway pressure and behavioral therapy for those with at least mild OSA or (2) standard therapy. The primary end point was the change in the plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level from baseline to the 7-month follow-up.

Results: A total of 159 patients completed the trial. Of the 70 patients randomized to SGMT, 21 (30%), 15 (22%) and 27 (39%) were diagnosed with mild, moderate and severe OSA, respectively. Continuous positive airway pressure and a positional pillow were prescribed to 57 (91%) and 6 (9%) patients with OSA. Although plasma NT-proBNP levels were lower after 7 months compared to the baseline, the levels did not differ significantly between the SGMT and standard therapy groups at baseline (579 ± 1117 vs. 611 ± 899 pg/dL, p = .851) or at 7 months (90 ± 167 vs. 93 ± 174 pg/dL, p = .996). The changes in NT-proBNP levels from baseline to 7 months were similar with SGMT and standard therapy (-489 vs. -518 pg/dL, p = .726). Similar findings were observed for the plasma ST2 and hs-CRP levels.

Conclusions: OSA screening and multifaceted treatment during the sub-acute phase of acute coronary syndrome did not further reduce the levels of cardiovascular biomarkers when compared with standard therapy.

Clinical Trial Registration: clinicaltrial.gov NCT02599298.
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http://dx.doi.org/10.1016/j.ijcard.2019.07.003DOI Listing
January 2020
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