Atherosclerotic cardiovascular disease landscape in Singapore.

Cardiovascular disease (CVD) is the leading cause of death worldwide, accounting for over one-third of all deaths in Singapore. An analysis of age-standardized mortality rates (ASMR) for CVD in Singapore revealed a deceleration in the initial rapid decline in ASMR. A decrease in smoking prevalence may have contributed to the initial rapid decline in ASMR. Furthermore, other major risk factors, such as diabetes mellitus, hypertension, elevated low-density lipoprotein levels, and obesity, are steadily rising. Singapore's CVD economic burden is estimated to be 8.1 billion USD (11.5 billion SGD). The burden of CVD can only be reduced using individual and population-based approaches. Prevention programs must also be developed based on an understanding of risk trends. Therefore, this article attempts to capture the burden of CVD, trends in risk factor control, preventive care, disparities, and current unmet needs, particularly in atherosclerotic cardiovascular disease management in Singapore.

Healthcare in the era of climate change and the need for environmental sustainability.

ABSTRACT: Climate change is an existential threat to humanity. While the healthcare sector must manage the health-related consequences of climate change, it is a significant contributor to greenhouse gas emissions, responsible for up to 4.6% of global emission, aggravating global warming. Within the hospital environment, the three largest contributors to greenhouse gas emissions are the operating theatre, intensive care unit and gastrointestinal endoscopy. Knowledge of the health-related burden of climate change and the potential transformative health benefits of climate action is important to all health professionals, as they play crucial roles in effecting change. This article summarises the available literature on the impact of healthcare on climate change and efforts in mitigation, focusing on the intrinsic differences and similarities across the operating theatre complex, intensive care unit and gastrointestinal endoscopy unit. It also discusses strategies to reduce carbon footprint.

Left Ventricular Diastolic Dysfunction Is Associated with Poor Functional Outcomes after Endovascular Thrombectomy.

INTRODUCTION: With the advent of endovascular thrombectomy (ET), patients with acute ischaemic strokes (AIS) with large vessel occlusion (LVO) have seen vast improvements in treatment outcomes. Left ventricular diastolic dysfunction (LVDD) has been shown to herald poorer prognosis in conditions such as myocardial infarction. However, whether LVDD is related to functional recovery and outcomes in ischaemic stroke remains unclear. We studied LVDD for possible relation with clinical outcomes in patients with LVO AIS who underwent ET. METHODS: We studied a retrospective cohort of 261 LVO AIS patients who had undergone ET at a single comprehensive stroke centre and correlated LVDD to short-term mortality (in-hospital death) as well as good functional recovery defined as modified Rankin Scale of 0-2 at 3 months. RESULTS: The study population had a mean age of 65-years-old and were predominantly male (54.8%). All of the patients underwent ET with 206 (78.9%) achieving successful reperfusion. Despite this, 25 (9.6%) patients demised during the hospital admission and 149 (57.1%) did not have good function recovery at 3 months. LVDD was present in 82 (31.4%) patients and this finding indicated poorer outcomes in terms of functional recovery at 3 months (OR 2.18, 95% CI 1.04-4.54, p = 0.038) but was not associated with increased in-hospital mortality (OR 2.18, 95% CI 0.60-7.99, p = 0.240) after adjusting for various confounders. CONCLUSION: In addition to conventional echocardiographic indices such as left ventricular ejection fraction, LVDD may portend poorer outcomes after ET, and this relationship should be investigated further.

Use of wearable technology in cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source: a systematic review.

INTRODUCTION: Prolonged cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source (ESUS) is necessary to identify atrial fibrillation (AF) that requires anticoagulation. Wearable devices may improve AF detection compared to conventional management. We aimed to review the evidence for the use of wearable devices in post-cryptogenic stroke and post-ESUS monitoring. METHODS: We performed a systematic search of PubMed, EMBASE, Scopus and clinicaltrials.gov on 21 July 2022, identifying all studies that investigated the use of wearable devices in patients with cryptogenic stroke or ESUS. The outcomes of AF detection were analysed. Literature reports on electrocardiogram (ECG)-based (external wearable, handheld, patch, mobile cardiac telemetry [MCT], smartwatch) and photoplethysmography (PPG)-based (smartwatch, smartphone) devices were summarised. RESULTS: A total of 27 relevant studies were included (two randomised controlled trials, seven prospective trials, 10 cohort studies, six case series and two case reports). Only four studies compared wearable technology to Holter monitoring or implantable loop recorder, and these studies showed no significant differences on meta-analysis (odds ratio 2.35, 95% confidence interval [CI] 0.74-7.48, I 2 = 70%). External wearable devices detected AF in 20.7% (95% CI 14.9-27.2, I 2 = 76%) of patients and MCT detected new AF in 9.6% (95% CI 7.4%-11.9%, I 2 = 56%) of patients. Other devices investigated included patch sensors, handheld ECG recorders and PPG-based smartphone apps, which demonstrated feasibility in the post-cryptogenic stroke and post-ESUS setting. CONCLUSION: Wearable devices that are ECG or PPG based are effective for paroxysmal AF detection after cryptogenic stroke and ESUS, but further studies are needed to establish how they compare with Holter monitors and implantable loop recorder.

Increased left ventricular remodelling index in paradoxical low-flow severe aortic stenosis with preserved left ventricular ejection fraction compared to normal-flow severe aortic stenosis.

INTRODUCTION: Patients with paradoxical low-flow (LF) severe aortic stenosis (AS) despite preserved left ventricular ejection fraction (LVEF) appear distinct from normal-flow (NF) patients, showing worse prognosis, more concentric hypertrophy and smaller left ventricular (LV) cavities. The left ventricular remodelling index (LVRI) has been demonstrated to reliably discriminate between physiologically adapted athlete's heart and pathological LV remodelling. METHODS: We studied patients with index echocardiographic diagnosis of severe AS (aortic valve area <1 cm2) with preserved LVEF (>50%). The LVRI was determined by the ratio of the LV mass to the end-diastolic volume, as previously reported, and was compared between patients with LF and NF AS. Patients were prospectively followed up for at least 3 years, and clinical outcomes were examined in association with LVRI. RESULTS: Of the 450 patients studied, 112 (24.9%) had LF AS. While there were no significant differences in baseline clinical profile between LF and NF patients, LVRI was significantly higher in the LF group. Patients with high LVRI (>1.56 g/mL) had increased all-cause mortality (log-rank 9.18, P = 0.002) and were more likely to be admitted for cardiac failure (log-rank 7.61, P = 0.006) or undergo aortic valve replacement (log-rank 18.4, P < 0.001). After adjusting for the effect of age, hypertension, aortic valve area and mean pressure gradient on multivariate Cox regression, high LVRI remained independently associated with poor clinical outcomes (hazard ratio 1.64, 95% confidence interval 1.19-2.25, P = 0.002). CONCLUSION: Pathological LV remodelling (increased LVRI) was more common in patients with LF AS, and increased LVRI independently predicts worse clinical outcomes.

Efficacy and Safety of Inclisiran in Asian Patients: Results From ORION-18.

Background: Management of low-density lipoprotein cholesterol (LDL-C) in Asia remains suboptimal, with ∼50% of patients who are treated with lipid-lowering therapies (LLTs) unable to achieve their guideline-recommended LDL-C goals. Asian-representative studies of the use of inclisiran are needed. Objectives: The authors sought to evaluate the efficacy and safety of inclisiran in Asian patients with atherosclerotic cardiovascular disease (ASCVD) or high risk of ASCVD, as an adjunct to diet and maximally tolerated statin dose, with or without additional LLTs. Methods: The ORION-18 was a phase 3 double-blind trial in which patients were randomized 1:1 to receive either 300 mg inclisiran sodium or matching placebo on days 1, 90, and 270. Percentage change in LDL-C from baseline to day 330 was the primary endpoint. Results: A total of 345 patients (mean age 59.5 years, mean baseline LDL-C 109 mg/dL, 74.7% male) were randomized to inclisiran or placebo. Baseline characteristics were similar in both groups. The percentage decrease in LDL-C from baseline to day 330 was 57.2% (P < 0.001); proprotein convertase subtilisin/kexin type 9 was reduced by 78.3% (P < 0.001). Time-adjusted percentage reduction in LDL-C from baseline after day 90 and up to day 360 was 56.3%. At day 330, 71.7% of participants with inclisiran achieved ≥50% reduction in LDL-C compared with 1.5% with placebo. Over the study period, total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol (HDL-C) levels were decreased significantly, and HDL-C levels increased. The incidence of adverse events with inclisiran was similar to that with placebo. Conclusions: In Asian patients with ASCVD or high risk of ASCVD, inclisiran was effective and safe. (Study of Efficacy and Safety of Inclisiran in Asian Participants With Atherosclerotic Cardiovascular Disease [ASCVD] or ASCVD High Risk and Elevated Low-Density Lipoprotein Cholesterol [LDL-C] [ORION-18]; NCT04765657).

Left ventricular vortex formation time: emerging clinical applications and limitations.

Vortex formation during left ventricular diastolic filling may provide clinically useful insights into cardiac health. In recent years, there has been growing interest in the measurement of vortex formation time (VFT), especially because it is derived noninvasively. There are important applications of VFT in valvular heart disease, athletic physiology, heart failure and hypertrophic cardiomyopathy. The formation of the vortex as fluid propagates into the left ventricle from the left atrium is important for efficient fluid transport. Quantifying VFT may thus help in evaluating and understanding disease and pathophysiological processes.

American Society of Echocardiography COVID-19 Statement Update: Lessons Learned and Preparation for Future Pandemics.

The COVID-19 pandemic has evolved since the publication of the initial American Society of Echocardiography (ASE) statements providing guidance to echocardiography laboratories. In light of new developments, the ASE convened a diverse, expert writing group to address the current state of the COVID-19 pandemic and to apply lessons learned to echocardiography laboratory operations in future pandemics. This statement addresses important areas specifically impacted by the current and future pandemics: (1) indications for echocardiography, (2) application of echocardiographic services in a pandemic, (3) infection/transmission mitigation strategies, (4) role of cardiac point-of-care ultrasound/critical care echocardiography, and (5) training in echocardiography.

Yeo's index: A novel index that combines anatomic and haemodynamic assessment of the severity of mitral stenosis.

BACKGROUND: A mitral leaflet separation index (MLSI), measuring the anatomical separation of the mitral valve (MV) leaflet tips in diastole, was previously described as an accurate method of assessing mitral stenosis (MS). We propose a novel modification of the MLSI by including a hemodynamic assessment which we term Yeo's index that may improve its diagnostic performance. METHODS AND RESULTS: We retrospectively studied 174 patients with varying severity of MS without significant mitral regurgitation, aortic valve disease or ventricular septal defect. MLSI was measured in 2 orthogonal views on transthoracic echocardiography as previously described. MV dimensionless index (DI) was calculated by dividing the left ventricular outflow tract pulsed-wave Doppler time velocity integral (TVI) by the MV continuous-wave Doppler TVI. We defined Yeo's index as the product of MLSI and DI. With linear correlation, Yeo's index demonstrated good correlation against MVA by planimetry (r = 0.728), pressure half-time (r = 0.677), and continuity equation (r = 0.829), with improved performance over the MLSI. Using ROC analysis, Yeo's index demonstrated good ability to correctly classify MS as severe (MVA ≤1.5cm2) (AUC 0.874, 95% CI 0.816-0.920). Yeo's index ≤0.260 cm correctly classified severe MS with sensitivity of 82% and specificity of 80%. Presence of AF did not affect the performance of Yeo's index. Yeo's index ≤0.147 cm also identified very severe MS (MVA ≤ 1.0 cm2) with specificity of 94% and sensitivity of 78%. CONCLUSION: Yeo's index performed well in identifying severe MS and may be a useful adjunct to existing measures of MS severity.

Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS: Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS: Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION: Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.

Impact of Complete Revascularization in the ISCHEMIA Trial.

BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported. OBJECTIVES: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management. METHODS: ACR and FCR in the INV group were assessed at an independent core laboratory. Multivariable-adjusted outcomes of CR were examined in INV patients. Inverse probability weighted modeling was then performed to estimate the treatment effect had CR been achieved in all INV patients compared with CON management. RESULTS: ACR and FCR were achieved in 43.4% and 58.4% of 1,824 INV patients. ACR was associated with reduced 4-year rates of cardiovascular death or MI compared with incomplete revascularization. By inverse probability weighted modeling, ACR in all 2,296 INV patients compared with 2,498 CON patients was associated with a lower 4-year rate of cardiovascular death or MI (difference -3.5; 95% CI: -7.2% to 0.0%). In comparison, the event rate difference of cardiovascular death or MI for INV minus CON in the overall ISCHEMIA trial was -2.4%. Results were similar but less pronounced with FCR. CONCLUSIONS: The outcomes of an INV strategy may be improved if CR (especially ACR) is achieved. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Impact of complete revascularization in the IschemiaTrial

BACKGROUND: Anatomic complete revascularization (ACR) and functional complete revascularization (FCR) have been associated with reduced death and myocardial infarction (MI) in some prior studies. The impact of complete revascularization (CR) in patients undergoing an invasive (INV) compared with a conservative (CON) management strategy has not been reported. OBJECTIVES: Among patients with chronic coronary disease without prior coronary artery bypass grafting randomized to INV vs CON management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, we examined the following: 1) the outcomes of ACR and FCR compared with incomplete revascularization; and 2) the potential impact of achieving CR in all INV patients compared with CON management. METHODS: ACR and FCR in the INV group were assessed at an independent core laboratory. Multivariable-adjusted outcomes of CR were examined in INV patients. Inverse probability weighted modeling was then performed to estimate the treatment effect had CR been achieved in all INV patients compared with CON management. RESULTS: ACR and FCR were achieved in 43.4% and 58.4% of 1,824 INV patients. ACR was associated with reduced 4-year rates of cardiovascular death or MI compared with incomplete revascularization. By inverse probability weighted modeling, ACR in all 2,296 INV patients compared with 2,498 CON patients was associated with a lower 4-year rate of cardiovascular death or MI (difference -3.5; 95% CI: -7.2% to 0.0%). In comparison, the event rate difference of cardiovascular death or MI for INV minus CON in the overall ISCHEMIA trial was -2.4%. Results were similar but less pronounced with FCR. CONCLUSIONS: The outcomes of an INV strategy may be improved if CR (especially ACR) is achieved. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Left Ventricular Ejection Fraction Association with Acute Ischemic Stroke Outcomes in Patients Undergoing Thrombolysis.

(1) Background: Little is known about how left ventricular systolic dysfunction (LVSD) affects functional and clinical outcomes in acute ischemic stroke (AIS) patients undergoing thrombolysis; (2) Methods: A retrospective observational study conducted between 2006 and 2018 included 937 consecutive AIS patients undergoing thrombolysis. LVSD was defined as left ventricular ejection fraction (LVEF) < 50%. Univariate and multivariate binary logistic regression analysis was performed for demographic characteristics. Ordinal shift regression was used for functional modified Rankin Scale (mRS) outcome at 3 months. Survival analysis of mortality, heart failure (HF) admission, myocardial infarction (MI) and stroke/transient ischemic attack (TIA) was evaluated with a Cox-proportional hazards model; (3) Results: LVSD patients in comparison with LVEF ≥ 50% patients accounted for 190 and 747 patients, respectively. LVSD patients had more comorbidities including diabetes mellitus (100 (52.6%) vs. 280 (37.5%), p < 0.001), atrial fibrillation (69 (36.3%) vs. 212 (28.4%), p = 0.033), ischemic heart disease (130 (68.4%) vs. 145 (19.4%), p < 0.001) and HF (150 (78.9%) vs. 46 (6.2%), p < 0.001). LVSD was associated with worse functional mRS outcomes at 3 months (adjusted OR 1.41, 95% CI 1.03-1.92, p = 0.030). Survival analysis identified LVSD to significantly predict all-cause mortality (adjusted HR [aHR] 3.38, 95% CI 1.74-6.54, p < 0.001), subsequent HF admission (aHR 4.23, 95% CI 2.17-8.26, p < 0.001) and MI (aHR 2.49, 95% CI 1.44-4.32, p = 0.001). LVSD did not predict recurrent stroke/TIA (aHR 1.15, 95% CI 0.77-1.72, p = 0.496); (4) Conclusions: LVSD in AIS patients undergoing thrombolysis was associated with increased all-cause mortality, subsequent HF admission, subsequent MI and poorer functional outcomes, highlighting a need to optimize LVEF.

Clinical profile and outcomes in patients with moderate to severe aortic stenosis with or without concomitant chronic kidney disease.

Introduction: Management of aortic stenosis (AS) in patients with chronic kidney disease (CKD) may often be overlooked, and this could confer poorer outcomes. Methods: Consecutive patients (n = 727) with index echocardiographic diagnosis of moderate to severe AS (aortic valve area <1.5 cm2) were examined. They were divided into those with CKD (estimated glomerular filtration rate < 60 mL/min) and those without. Baseline clinical and echocardiographic parameters were compared, and a multivariate Cox regression model was constructed. Clinical outcomes were compared using Kaplan-Meier curves. Results: There were 270 (37.1%) patients with concomitant CKD. The CKD group was older (78.0 ± 10.3 vs. 72.1 ± 12.9 years, P < 0.001), with a higher prevalence of hypertension, diabetes mellitus, hyperlipidaemia and ischaemic heart disease. AS severity did not differ significantly, but left ventricular (LV) mass index (119.4 ± 43.7 vs. 112.3 ± 40.6 g/m2, P = 0.027) and Doppler mitral inflow E to annular tissue Doppler e' ratio (E: e' 21.5 ± 14.6 vs. 17.8 ± 12.2, P = 0.001) were higher in the CKD group. There was higher mortality (log-rank 51.5, P < 0.001) and more frequent admissions for cardiac failure (log-rank 25.9, P < 0.001) in the CKD group, with a lower incidence of aortic valve replacement (log-rank 7.12, P = 0.008). On multivariate analyses, after adjusting for aortic valve area, age, left ventricular ejection fraction and clinical comorbidities, CKD remained independently associated with mortality (hazard ratio 1.96, 95% confidence interval 1.50-2.57, P < 0.001). Conclusion: Concomitant CKD in patients with moderate to severe AS was associated with increased mortality, more frequent admissions for cardiac failure and a lower incidence of aortic valve replacement.