Publications by authors named "Adrian F Low"

82 Publications

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

The association of genetically determined serum glycine with cardiovascular risk in East Asians.

Nutr Metab Cardiovasc Dis 2021 06 7;31(6):1840-1844. Epub 2021 Apr 7.

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore; Khoo Teck Puat, National University Children's Medical Institute, National University Health System, Singapore 119074, Singapore. Electronic address:

Background And Aims: Glycine is involved in a wide range of metabolic pathways and increased circulating glycine is associated with reduced risk of cardio-metabolic diseases in Europeans but the genetic association between circulating glycine and cardiovascular risk is largely unknown in East Asians.

Methods And Results: We conducted a genome-wide association study (GWAS) in Singaporean Chinese participants and investigated if genetically determined serum glycine were associated with incident coronary artery disease (CAD) (711 cases and 1,246 controls), cardiovascular death (1,886 cases and 21,707 controls) and angiographic CAD severity (as determined by the Modified Gensini score, N = 1,138).

Conclusion: Our study, a first in East Asians, suggest a protective role of glycine against CAD.
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http://dx.doi.org/10.1016/j.numecd.2021.03.010DOI Listing
June 2021

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

J Thromb Thrombolysis 2021 Oct 6;52(3):925-933. 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
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 09 20;37(9):1450-1459. 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
September 2021

OCT and IVUS Appearance of a Neointimal Dissection Within a Recently Implanted Left Main Stent.

JACC Cardiovasc Interv 2021 02 27;14(4):e31-e35. Epub 2021 Jan 27.

Department of Cardiology, National Heart Centre, Singapore.

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http://dx.doi.org/10.1016/j.jcin.2020.11.017DOI Listing
February 2021

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

Open Heart 2021 01;8(1)

Cardiology, National University Heart Centre, Singapore.

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

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

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

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

Interaction between a haptoglobin genetic variant and coronary artery disease (CAD) risk factors on CAD severity in Singaporean Chinese population.

Mol Genet Genomic Med 2020 10 13;8(10):e1450. Epub 2020 Aug 13.

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

Background: Haptoglobin (Hp) is a plasma protein with strong anti-inflammation and antioxidant activities. Its plasma level is known to be inversely associated with many inflammatory diseases, including cardiovascular diseases. However, the association of HP genetic variants with coronary artery disease (CAD) severity/mortality, and how they interact with common CAD risk factors are largely unknown.

Methods: We conducted the analysis in a Singaporean Chinese CAD population with Gensini severity scores (N = 582) and subsequently evaluated the significant findings in an independent cohort with cardiovascular mortality (excluding stroke) as outcome (917 cases and 19,093 controls). CAD risk factors were ascertained from questionnaires, and stenosis information from medical records. Mortality was identified through linkage with the nationwide registry of births and deaths in Singapore. Linear regression analysis between HP genetic variant (rs217181) and disease outcome were performed. Interaction analyses were performed by introducing an interaction term in the same regression models.

Results: Although rs217181 was not significantly associated with CAD severity and cardiovascular mortality (excluding stroke) in all subjects, when stratified by hypertension status, hypertensive individuals with the minor T allele have more severe CAD (β = 0.073, SE = 0.030, p = 0.015) and non-hypertensive individuals with the T allele have lower risk for mortality (odds ratio = 0.771 (0.607-0.980), p = 0.033).

Conclusion: HP genetic variant is not associated with CAD severity and mortality in the general population. However, hypertensive individuals with the rs217181 T allele associated with higher Hp levels had more severe CAD while non-hypertensive individuals with the same allele had lower risk for mortality in the Chinese population.
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http://dx.doi.org/10.1002/mgg3.1450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7549588PMC
October 2020

Quantification of effects of mean blood pressure and left ventricular mass on noninvasive fast fractional flow reserve.

Am J Physiol Heart Circ Physiol 2020 08 17;319(2):H360-H369. Epub 2020 Jul 17.

National Heart Centre Singapore, Singapore.

Proper inlet boundary conditions are essential for accurate computational fluid dynamics (CFD) modeling. We developed methodology to derive noninvasive FFR using CFD and computed tomography coronary angiography (CTCA) images. This study aims to assess the influence of brachial mean blood pressure (MBP) and total coronary inflow on FFR computation. Twenty-two patients underwent both CTCA and FFR measurements. Total coronary flow was computed from left ventricular mass (LVM) measured from CTCA. A total of 286 CFD simulations were run by varying MBP and LVM at 70, 80, 90, 100, 110, 120, and 130% of the measured values. FFR increased with incrementally higher input values of MBP: 0.78 ± 0.12, 0.80 ± 0.11, 0.82 ± 0.10, 0.84 ± 0.09, 0.85 ± 0.08, 0.86 ± 0.08, and 0.87 ± 0.07, respectively. Conversely, FFR decreased with incrementally higher inputs value of LVM: 0.86 ± 0.08, 0.85 ± 0.08, 0.84 ± 0.09, 0.84 ± 0.09, 0.83 ± 0.10, 0.83 ± 0.10, and 0.82 ± 0.10, respectively. Noninvasive FFR calculated using measured MBP and LVM on a total of 30 vessels was 0.84 ± 0.09 and correlated well with invasive FFR (0.83 ± 0.09) ( = 0.92, < 0.001). Positive association was observed between FFR and MBP input values (mmHg) and negative association between FFR and LVM values (g). Respective slopes were 0.0016 and -0.005, respectively, suggesting potential application of FFR in a clinical setting. Inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. While brachial mean blood pressure (MBP) and left ventricular mass (LVM) measured from CTCA are the two CFD simulation input parameters, their effects on noninvasive fractional flow reserve (FFR) have not been systematically investigated. We demonstrate that inaccurate MBP and LVM inputs differing from patient-specific values could result in misclassification of borderline ischemic lesions. This is important in the clinical application of noninvasive FFR in coronary artery disease diagnosis.
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http://dx.doi.org/10.1152/ajpheart.00135.2020DOI Listing
August 2020

Causes and prognosis of symptomatic pericardial effusions treated by pericardiocentesis in an Asian academic medical centre.

Singapore Med J 2020 Mar 11;61(3):137-141. Epub 2019 Jul 11.

Department of Cardiology, National University Heart Centre, Singapore.

Introduction: This study aimed to investigate the causes, clinical management and outcomes of clinically significant pericardial effusions, and evaluate the practice of pericardiocentesis within an academic medical centre in Singapore, a multiethnic country in Southeast Asia.

Methods: Consecutive patients undergoing pericardiocentesis at a single Asian academic medical centre were identified. Patient demographics, echocardiographic findings, investigations, pericardiocentesis procedural details and clinical progress were tracked using a comprehensive electronic medical records system.

Results: Of 149 patients who underwent pericardiocentesis, malignancy (46.3%) was the most common cause of pericardial effusions, followed by iatrogenic postsurgical complications (17.4%). 77.3% of effusions were large and 69.8% demonstrated tamponade physiology. Pericardiocentesis guided by echocardiography and fluoroscopy was successful in 99.3% of patients and had a complication rate of 2.0%. Likelihood of effusion recurrence and survival to discharge was determined by the aetiology of the pericardial effusion. 24.6% of malignant effusions recurred, and the survival rate 12 months after drainage of a malignant pericardial effusion was 45.0%. Short-term mortality was highest among patients presenting with tamponade due to acute aortic syndromes and those with myocardial rupture due to ischaemic heart disease.

Conclusion: Cancer and iatrogenic complications were the most common causes of pericardial effusion in this large cohort of Singapore patients. Pericardiocentesis has a high success rate and relatively low complication rate. Prognosis and clinical course after pericardiocentesis are determined by the underlying cause of the pericardial effusion.
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http://dx.doi.org/10.11622/smedj.2019065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905117PMC
March 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

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

Sex Differences in 1-Year Rehospitalization for Heart Failure and Myocardial Infarction After Primary Percutaneous Coronary Intervention.

Am J Cardiol 2019 06 19;123(12):1935-1940. Epub 2019 Mar 19.

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

It is unclear whether universal access to primary percutaneous coronary intervention (pPCI) may reduce sex differences in 1-year rehospitalization for heart failure (HF) and myocardial infarction (MI) after ST-elevation myocardial infarction (STEMI). We studied 7,597 consecutive STEMI patients (13.8% women, n = 1,045) who underwent pPCI from January 2007 to December 2013. Cox regression models adjusted for competing risk from death were used to assess sex differences in rehospitalization for HF and MI within 1 year from discharge. Compared with men, women were older (median age 67.6 vs 56.0 years, p < 0.001) with higher prevalence of co-morbidities and multivessel disease. Women had longer median door-to-balloon time (76 vs 66 minutes, p < 0.001) and were less likely to receive drug-eluting stents (19.5% vs 24.1%, p = 0.001). Of the medications prescribed at discharge, fewer women received aspirin (95.8% vs 97.6%, p = 0.002) and P2Y antagonists (97.6% vs 98.5%, p = 0.039), but there were no significant sex differences in other discharge medications. After adjusting for differences in baseline characteristics and treatment, sex differences in risk of rehospitalization for HF attenuated (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.79 to 1.40), but persisted for MI (HR 1.68, 95% CI 1.22 to 2.33), with greater disparity in patients aged ≥60 years (HR 1.83, 95% CI 1.18 to 2.85) than those aged <60 years (HR 1.45, 95% CI 0.84 to 2.50). In conclusion, in a setting of universal access to pPCI, the adjusted risk of 1-year rehospitalization for HF was similar in both sexes, but women had significantly higher adjusted risk of 1-year rehospitalization for MI, especially older women.
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http://dx.doi.org/10.1016/j.amjcard.2019.03.021DOI Listing
June 2019

Combining Circulating MicroRNA and NT-proBNP to Detect and Categorize Heart Failure Subtypes.

J Am Coll Cardiol 2019 03;73(11):1300-1313

Cardiovascular Research Institute, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cardiac Department, National University Health System, Singapore; Christchurch Heart Institute, University of Otago, Christchurch, New Zealand. Electronic address:

Background: Clinicians need improved tools to better identify nonacute heart failure with preserved ejection fraction (HFpEF).

Objectives: The purpose of this study was to derive and validate circulating microRNA signatures for nonacute heart failure (HF).

Methods: Discovery and validation cohorts (N = 1,710), comprised 903 HF and 807 non-HF patients from Singapore and New Zealand (NZ). MicroRNA biomarker panel discovery in a Singapore cohort (n = 546) was independently validated in a second Singapore cohort (Validation 1; n = 448) and a NZ cohort (Validation 2; n = 716).

Results: In discovery, an 8-microRNA panel identified HF with an area under the curve (AUC) 0.96, specificity 0.88, and accuracy 0.89. Corresponding metrics were 0.88, 0.66, and 0.77 in Validation 1, and 0.87, 0.58, and 0.74 in Validation 2. Combining microRNA panels with N-terminal pro-B-type natriuretic peptide (NT-proBNP) clearly improved specificity and accuracy from AUC 0.96, specificity 0.91, and accuracy 0.90 for NT-proBNP alone to corresponding metrics of 0.99, 0.99, and 0.93 in the discovery and 0.97, 0.96, and 0.93 in Validation 1. The 8-microRNA discovery panel distinguished HFpEF from HF with reduced ejection fraction with AUC 0.81, specificity 0.66, and accuracy 0.72. Corresponding metrics were 0.65, 0.41, and 0.56 in Validation 1 and 0.65, 0.41, and 0.62 in Validation 2. For phenotype categorization, combined markers achieved AUC 0.87, specificity 0.75, and accuracy 0.77 in the discovery with corresponding metrics of 0.74, 0.59, and 0.67 in Validation 1 and 0.72, 0.52, and 0.68 in Validation 2, as compared with NT-proBNP alone of AUC 0.71, specificity 0.46, and accuracy 0.62 in the discovery; with corresponding metrics of 0.72, 0.44, and 0.57 in Validation 1 and 0.69, 0.48, and 0.66 in Validation 2. Accordingly, false negative (FN) (81% Singapore and all NZ FN cases were HFpEF) as classified by a guideline-endorsed NT-proBNP ruleout threshold, were correctly reclassified by the 8-microRNA panel in the majority (72% and 88% of FN in Singapore and NZ, respectively) of cases.

Conclusions: Multi-microRNA panels in combination with NT-proBNP are highly discriminatory and improved specificity and accuracy in identifying nonacute HF. These findings suggest potential utility in the identification of nonacute HF, where clinical assessment, imaging, and NT-proBNP may not be definitive, especially in HFpEF.
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http://dx.doi.org/10.1016/j.jacc.2018.11.060DOI 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

Three-year follow-up optical coherence tomography of under-expanded drug-eluting stent in-stent restenosis treated with ABSORB bioresorbable vascular scaffold following ultra-high pressure pre-dilatation.

J Cardiol Cases 2018 Jan 10;17(1):4-8. Epub 2017 Nov 10.

National University Heart Centre, Singapore.

The management of in-stent restenosis continues to be a common challenge in modern interventional cardiology. Drug-eluting stents have emerged to be an effective treatment following bare-metal stent in-stent restenosis as compared with drug-coated balloon angioplasty and repeat bare-metal stenting. The addition of another metallic layer is however undesirable and may limit further treatment options. In the last few years, everolimus-eluting bioresorbable vascular scaffolds have become available in treating native coronary artery disease with complete hydrolysis into water and carbon dioxide within 3-5 years. To exploit this property, we successfully used it to manage a case of drug-eluting stent in-stent restenosis from a previously under-expanded stent as demonstrated in this case. Small registry series have also recently been published supporting favorable outcomes with this approach. To the best of our knowledge, this case has the longest optical coherence tomography follow-up beyond 3 years. < The dedicated dual-layer OPN NC balloon (Schwager Medica, Winterthur, Switzerland) could be used in the under-expanded metallic stent that is not overcome by conventional non-compliant balloons as demonstrated in our case. The application of bioresorbable vascular scaffold in drug-eluting stent in-stent restenosis has satisfactory medium- to long-term clinical outcome. The 3-year follow-up intracoronary study demonstrated complete tissue coverage of the scaffold. Complete bioresorption of the scaffold, by hydrolysis into carbon dioxide and water, takes approximately 3-5 years, thus avoiding another layer of metallic cage.>.
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http://dx.doi.org/10.1016/j.jccase.2017.08.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146415PMC
January 2018

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

Incidence and predictors of target lesion failure in a multiethnic Asian population receiving the SYNERGY coronary stent: A prospective all-comers registry.

Catheter Cardiovasc Interv 2018 11 7;92(6):1097-1103. Epub 2018 Mar 7.

Department of Cardiology, National University Heart Centre, Singapore.

Objectives: To evaluate the target lesion failure (TLF) rate of the SYNERGY stent in all-comers, multiethnic Asian population.

Background: Currently, most drug eluting stents deliver anti-proliferative drugs from a durable polymer which is associated with a risk of late stent thrombosis. The novel everolimus-eluting, platinum chromium SYNERGY stent is coated with a bioabsorbable abluminal polymer that resolves within 4 months.

Methods: This was a prospective, single center registry of consecutive patients treated with the SYNERGY stent between December 2012 and April 2015. The primary outcome was the incidence of TLF, defined as the combination of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization (TLR) at 1 year.

Results: A total of 807 patients received the SYNERGY stent during the study period. One-year clinical outcome data was available for 765 patients (94.8%) and were considered for statistical analysis. The mean age was 60.7 ± 10.8 years, and 83.4% were males. Patients with acute myocardial infarction consisted of 50.3% (ST-segment elevation myocardial infarction: 23.0%, Non-ST-segment elevation myocardial infarction: 27.3%) of the study population. The treated lesions were complex (ACC/AHA type B2/C: 72.7%). The primary end point of TLF at 1 year was 5.8%. Rates of cardiac mortality, target vessel myocardial infarction, and TLR were 4.2, 1.0, and 1.3%, respectively, at 1 year. Predictors of the incidence and time to early TLF were female gender, Malay ethnicity, diabetes mellitus, acute myocardial infarction at presentation, a prior history of coronary artery bypass surgery and the presence of lesion calcification. The incidence of definite stent thrombosis was 0.4% at 1 year.

Conclusions: In this registry, the use of the SYNERGY stent was associated with low rates of TLF at 1 year.
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http://dx.doi.org/10.1002/ccd.27577DOI Listing
November 2018

Prognostic Implications of Dual Platelet Reactivity Testing in Acute Coronary Syndrome.

Thromb Haemost 2018 02 29;118(2):415-426. Epub 2018 Jan 29.

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

Studies on platelet reactivity (PR) testing commonly test PR only after percutaneous coronary intervention (PCI) has been performed. There are few data on pre- and post-PCI testing. Data on simultaneous testing of aspirin and adenosine diphosphate antagonist response are conflicting. We investigated the prognostic value of combined serial assessments of high on-aspirin PR (HASPR) and high on-adenosine diphosphate receptor antagonist PR (HADPR) in patients with acute coronary syndrome (ACS). HASPR and HADPR were assessed in 928 ACS patients before (initial test) and 24 hours after (final test) coronary angiography, with or without revascularization. Patients with HASPR on the initial test, compared with those without, had significantly higher intraprocedural thrombotic events (IPTE) (8.6 vs. 1.2%,  ≤ 0.001) and higher 30-day major adverse cardiovascular and cerebrovascular events (MACCE; 5.2 vs. 2.3%,  = 0.05), but not 12-month MACCE (13.0 vs. 15.1%,  = 0.50). Patients with initial HADPR, compared with those without, had significantly higher IPTE (4.4 vs. 0.9%,  = 0.004), but not 30-day (3.5 vs. 2.3%,  = 0.32) or 12-month MACCE (14.0 vs. 12.5%,  = 0.54). The c-statistic of the Global Registry of Acute Coronary Events (GRACE) score alone, GRACE score + ASPR test and GRACE score + ADPR test for discriminating 30-day MACCE was 0.649, 0.803 and 0.757, respectively. Final ADPR was associated with 30-day MACCE among patients with intermediate-to-high GRACE score (adjusted odds ratio [OR]: 4.50, 95% confidence interval [CI]: 1.14-17.66), but not low GRACE score (adjusted OR: 1.19, 95% CI: 0.13-10.79). In conclusion, both HASPR and HADPR predict ischaemic events in ACS. This predictive utility is time-dependent and risk-dependent.
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http://dx.doi.org/10.1160/TH17-08-0564DOI Listing
February 2018

Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia.

Sci Rep 2017 12 20;7(1):17921. Epub 2017 Dec 20.

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore; and Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore, Singapore.

Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits (P < 5 × 10) were further evaluated in 291 CAD cases and 1,848 controls of Asian Indians. Using all datasets, we validated recently identified loci associated with CAD. The involvement of known canonical pathways in CAD was tested by Ingenuity Pathway Analysis. We identified a missense SNP (rs2075291, G > T, G185C) in APOA5 for CAD that reached robust genome-wide significance (Meta P = 7.09 × 10, OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5. We further replicated 10 loci previously identified among predominantly Europeans (P: 1.33 × 10-0.047). Seven pathways (P: 1.10 × 10-0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia.
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http://dx.doi.org/10.1038/s41598-017-18214-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5738399PMC
December 2017

Thymosin Beta-4 Is Elevated in Women With Heart Failure With Preserved Ejection Fraction.

J Am Heart Assoc 2017 Jun 13;6(6). Epub 2017 Jun 13.

Cardiovascular Research Institute, National University Health System, Singapore

Background: Thymosin beta-4 (TB4) is an X-linked gene product with cardioprotective properties. Little is known about plasma concentration of TB4 in heart failure (HF), and its relationship with other cardiovascular biomarkers. We sought to evaluate circulating TB4 in HF patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction compared to non-HF controls.

Methods And Results: TB4 was measured using a liquid chromatography and mass spectrometry assay in age- and sex-matched HFpEF (n=219), HFrEF (n=219) patients, and controls (n=219) from a prospective nationwide study. Additionally, a 92-marker multiplex proximity extension assay was measured to identify biomarker covariates. Compared with controls, plasma TB4 was elevated in HFpEF (985 [421-1723] ng/mL versus 1401 [720-2379] ng/mL, <0.001), but not in HFrEF (1106 [556-1955] ng/mL, =0.642). Stratifying by sex, only women (1623 [1040-2625] ng/mL versus 942 [386-1891] ng/mL, <0.001), but not men (1238.5 [586-1967] ng/mL versus 1004 [451-1538] ng/mL, =1.0), had significantly elevated TB4 in the setting of HFpEF. Adjusted for New York Heart Association class, N-terminal pro B-type natriuretic peptide, age, and myocardial infarction, hazard ratio to all-cause mortality is significantly higher in women with elevated TB4 (1.668, =0.036), but not in men (0.791, =0.456) with HF. TB4 is strongly correlated with a cluster of 7 markers from the proximity extension assay panel, which are either X-linked, regulated by sex hormones, or involved with NF-κB signaling.

Conclusions: We show that plasma TB4 is elevated in women with HFpEF and has prognostic information. Because TB4 can preserve EF in animal studies of cardiac injury, the relation of endogenous, circulating TB4 to X chromosome biology and differential outcomes in female heart disease warrants further study.
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http://dx.doi.org/10.1161/JAHA.117.005586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669175PMC
June 2017

Invasive Assessment of the Coronary Microcirculation in Reperfused ST-Segment-Elevation Myocardial Infarction Patients: Where Do We Stand?

Circ Cardiovasc Interv 2017 Mar;10(3)

From the Hatter Cardiovascular Institute, Institute of Cardiovascular Science, University College London, United Kingdom (H.B., D.J.H.); The National Institute of Health Research, University College London Hospitals, Biomedical Research Centre, United Kingdom (H.B., D.J.H.); Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore (H.B., N.F., D.J.H.); National Heart Research Institute Singapore, National Heart Centre Singapore (H.B., N.F., J.W.T., D.J.H.); National University Heart Centre, Singapore (A.F.L.); Department of Cardiology, Istanbul University, Istanbul Faculty of Medicine, Çapa, Turkey (M.S.); Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom (D.J.H.); and Yong Loo Lin School of Medicine, National University Singapore (D.J.H.).

For patients presenting with an acute ST-segment-elevation myocardial infarction, the most effective therapy for reducing myocardial infarct size and preserving left ventricular systolic function is primary percutaneous coronary intervention (PPCI). However, mortality and morbidity remain significant. This is partly attributed to the development of microvascular obstruction, which occurs in around 50% of ST-segment-elevation myocardial infarction patients post-PPCI, and it is associated with adverse left ventricular remodeling and worse clinical outcomes. Although microvascular obstruction can be detected by cardiac imaging techniques several hours post-PPCI, it may be too late to intervene at that time. Therefore, being able to predict the development of microvascular obstruction at the time of PPCI may identify high-risk patients who might benefit from further adjuvant intracoronary therapies, such as thrombolysis, vasodilators, glycoprotein IIb/IIIa inhibitors, and anti-inflammatory agents that may reduce microvascular obstruction. Recent studies have shown that invasive coronary physiology measurements performed during PPCI can be used to assess the coronary microcirculation. In this article, we provide an overview of the various invasive methods currently available to assess the coronary microcirculation in the setting of ST-segment-elevation myocardial infarction, and how they could potentially be used in the future for tailoring therapies to those most at risk.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.116.004373DOI Listing
March 2017

Bioresorbable vascular scaffold radial expansion and conformation compared to a metallic platform: insights from in vitro expansion in a coronary artery lesion model.

EuroIntervention 2016 09;12(7):834-44

National Heart Centre Singapore and Duke-NUS Medical School, Singapore.

Aims: This study aimed to compare the acute expansion behaviour of a polymer-based bioresorbable scaffold and a second-generation metallic DES platform in a realistic coronary artery lesion model. Experimental mechanical data with conventional methods have so far shown little difference between metallic stents and currently available polymer-based bioresorbable scaffolds (BRS). Nevertheless, differences in acute results have been observed in clinical studies comparing BRS directly with metallic DES platforms.

Methods And Results: We examined the expansion behaviour of the bioresorbable vascular scaffold (3.0×18 mm Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) and a metallic DES (3.0×18 mm XIENCE Prime; Abbott Vascular) after expansion at 37°C using identical coronary artery stenosis models (in total 12 experiments were performed). Device expansion was compared during balloon inflation and after deflation using microscopy to allow assessment of plaque recoil. Minimal lumen diameter (MLD) and minimal lumen area (MLA) and stent eccentricity were quantified from optical coherence tomography (OCT) imaging at nominal diameter and after post-dilation at 18 atm. The MLA in the models with BVS deployed was 4.92±0.17 mm² while in the metallic DES it was 5.40±0.13 mm2 (p=0.02) at nominal pressure (NP), and 5.41±0.20 and 6.07±0.25 mm2 (p=0.02), respectively, after expansion at 18 atm. Stent eccentricity index at the MLA was 0.71±0.02 in BVS compared to 0.81±0.02 in the metal stent at NP (p=0.004), and 0.73±0.03 compared to 0.75±0.02 at 18 atm (p=0.39).

Conclusions: Results obtained in this in vitro lesion model were comparable to the results in randomised clinical trials comparing BVS and XIENCE stents in vivo. Such models may be useful in future BRS developments to predict their acute response in vivo in eccentric lesions.
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http://dx.doi.org/10.4244/EIJV12I7A138DOI Listing
September 2016

Current practices of Asia-Pacific cardiologists in the utilization of bioresorbable scaffolds.

Int J Cardiol 2016 Nov 1;222:832-840. Epub 2016 Aug 1.

Hong Kong Sanatorium & Hospital, Hongkong, China.

Background & Aims: Although Absorb Bioresorbable Vascular Scaffolds (A-BVS) are routinely used in the Asia-Pacific, there is little information on patient selection or deployment technique here. This document investigates the experiences of leading interventional cardiologists from the Asia-Pacific region with a focus on patient characteristics, deployment techniques and management.

Methods And Results: A detailed questionnaire was distributed to 28 highly-experienced interventional cardiologists ('Authors') from 13 Asia-Pacific countries. The results were discussed at a meeting on patient selection, technical consideration, deployment practices and patient management. Potential patient benefits of Absorb compared to metallic DES, the learning curve for patient selection and preparation, device deployment, and subsequent patient management approaches are presented.

Conclusions: Current practices are derived from guidelines optimized for European patients. Differences in approach exist in the Asia-Pacific context, including limited access to imaging and frequency of occurrence of complex lesions. Nevertheless, the use of the Absorb BVS ('Absorb') in certain Asia-Pacific countries has flourished and practices here are continuing to mature.
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http://dx.doi.org/10.1016/j.ijcard.2016.07.273DOI Listing
November 2016

Coronary aneurysm without malapposition after bioresorbable vascular scaffold implantation.

EuroIntervention 2016 May;12(1):60

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

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http://dx.doi.org/10.4244/EIJV12I1A10DOI Listing
May 2016

How temporal evolution of intracranial collaterals in acute stroke affects clinical outcomes.

Neurology 2016 Feb 6;86(5):434-41. Epub 2016 Jan 6.

From the Division of Neurology, Department of Medicine (L.L.L.Y., P.P., R.C.S.S., A.A., B.P.L.C., H.L.T., D.S., R.R., V.K.S.), Cardiac Department (A.F.L., E.L.W.T.), and Department of Diagnostic Imaging (A.G., E.T.), National University Health System; Department of Neuroradiology (M.N.), National Neuroscience Institute; and Raffles Neuroscience Centre (N.V.), Raffles Medical Group, Singapore.

Objective: We compared intracranial collaterals on pretreatment and day 2 brain CT angiograms (CTA) to assess their evolution and relationship with functional outcomes in acute ischemic stroke (AIS) patients treated with IV tissue plasminogen activator (tPA).

Methods: Consecutive AIS patients who underwent pretreatment and day 2 CTA and received IV tPA during 2010-2013 were included. Collaterals were evaluated by 2 independent neuroradiologists using 3 predefined criteria: the Miteff system, the Maas system, and 20-point collateral scale by the Alberta Stroke Program Early CT Score methodology. We stratified our cohort by baseline pre-tPA state of their collaterals and by recanalization status of the primary vessel for analysis. Good outcomes at 3 months were defined by a modified Rankin Scale score of 0-1.

Results: This study included 209 patients. Delayed collateral recruitment by any grading system was not associated with good outcomes. All 3 scoring systems showed that collateral recruitment on the follow-up CTA from a baseline poor collateral state was significantly associated with poor outcome and increased bleeding risk. When the primary vessel remained persistently occluded, collateral recruitment was significantly associated with worse outcomes. Interestingly, collateral recruitment was significantly associated with increased mortality in 2 of the 3 grading systems.

Conclusions: Not all collateral recruitment is beneficial; delayed collateral recruitment may be different from early recruitment and can result in worse outcomes and higher mortality. Prethrombolysis collateral status and recanalization are determinants of how intracranial collateral evolution affects functional outcomes.
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http://dx.doi.org/10.1212/WNL.0000000000002331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773948PMC
February 2016
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