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Aims The cardioprotective effects of glucose‐lowering medications in diabetic patients with heart failure (HF) are well known. Several large randomized controlled trials (RCTs) have recently suggested that the cardioprotective effects of glucose‐lowering medications extend to HF patients regardless of diabetic status. The aim of this study was to conduct a Bayesian network meta‐analysis to evaluate the impact of various glucose‐lowering medications on the outcomes of non‐diabetic HF patients. Methods and results Medline and Embase were searched for RCTs investigating the use of glucose‐lowering medications in non‐diabetic HF patients in August 2021. Studies were included in accordance with the inclusion and exclusion criteria, and data were extracted with a pre‐defined datasheet. Primary outcomes include serum N‐terminal prohormone of brain natriuretic peptide (NT‐proBNP) levels, left ventricular ejection fraction (LVEF), and maximal oxygen consumption (PVO2). A Bayesian network meta‐analysis was performed to compare the effectiveness of different classes of glucose‐lowering medications in improving HF outcomes. Risk‐of‐bias was assessed using Cochrane Risk‐of‐Bias tool 2.0 for randomized trials (ROB2). Seven RCTs involving 2897 patients were included. Sodium‐glucose transporter 2 inhibitor (SGLT2i) was the most favourable in lowering NT‐proBNP, with the significant reduction in NT‐proBNP when compared with glucagon‐like peptide‐1 receptor agonists (GLP1‐RA) [mean differences (MD): −229.59 pg/mL, 95%‐credible intervals (95%‐CrI): −238.31 to −220.91], metformin (MD: −237.15 pg/mL, 95%‐CrI: −256.19 to −218.14), and placebo (MD: −228.00 pg/mL, 95%‐CrI: −233.99 to −221.99). SGLT2i was more effective in improving LVEF for HF with reduced ejection fraction patients relative to GLP1‐RA (MD: 8.09%, 95%‐CrI: 6.30 to 9.88) and placebo (MD: 6.10%, 95%‐CrI: 4.37 to 7.84). SGLT2i and GLP1‐RA were more favourable to placebo in improving PVO2, with significant increase of PVO2 at a MD of 1.60 mL/kg/min (95%‐CrI: 0.63 to 2.57) and 0.86 mL/kg/min (95%‐CrI: 0.66 to 1.06), respectively. All three drugs had comparable safety profiles when compared with placebo. Conclusions This Bayesian network meta‐analysis demonstrated that SGLT2i, when compared with GLP1‐RA and metformin, was superior in improving LVEF in HF with reduced ejection fraction patients, as well as improving PVO2 and NT‐proBNP in non‐diabetic HF patients. Further large‐scale prospective studies are needed to confirm these preliminary findings.

Patients with liver fibrosis and type 2 diabetes mellitus (T2DM) have an increased risk of cardiovascular events. However, long-term prognosis of liver fibrosis and T2DM after acute myocardial infarction (AMI) remain to be investigated. This study compared clinical characteristics and prognosis of AMI patients with T2DM and evidence of liver fibrosis. Patients were stratified into low, intermediate and high-risk for fibrosis, using serum-based non-invasive tests (NITs): Fibrosis-4 Index (FIB-4), Aspartate Aminotransferase to Platelet Ratio Index (APRI) and Non-alcoholic Fatty Liver Disease Fibrosis Score (NFS). The primary outcome was all-cause mortality, Kaplan-Meier curves were constructed for 5-year all-cause mortality. Cox regression analysis was used to determine the independent predictors of mortality, adjusting for confounders. Out of 3287 AMI patients, 1547 were stratified as high-risk by any NIT (mean follow-up duration 2.7 ± 2.3 years). A dose-response relationship was found with increasing mortality risk for higher APRI and NFS scores. High-risk FIB-4 also predicted mortality significantly (adjusted HR [aHR] 1.791, 95% CI 1.436–2.235, p  < 0.001). High-risk FIB-4 and APRI independently predicted mortality regardless of T2DM status, while NFS only predicted mortality in T2DM patients. Following AMI, individuals stratified by FIB-4, APRI, NFS as high-risk for liver fibrosis were associated with excess long-term mortality (aHR 1.780, 95% CI 1.442–2.196, p  < 0.001). Hence, readily available NITs may be beneficial in risk prognostication of AMI patients.

Background Emerging evidence has demonstrated the unfavourable cardiovascular risk of individuals with lean type 2 diabetes mellitus (T2DM). Our study aims to investigate the prognostic value of lean T2DM in patients with acute myocardial infarction (AMI), stratified by sex. Methods The study cohort examines the clinical characteristics and long-term outcomes of individuals with AMI, stratified by four phenotypes based on T2DM and lean body category—lean T2DM, non-lean T2DM, lean non-T2DM and non-lean non-T2DM. The primary outcome was long-term all-cause mortality. Cox regression model was constructed to investigate the associations of lean and non-lean T2DM phenotypes with mortality, adjusted for age, ethnicity, previous AMI, AMI type, chronic kidney disease, angiotensin converting enzyme inhibitor or angiotensin receptor blockers, beta-blockers, and smoking status. Results A cohort of 9545 AMI patients was examined, with a mean follow-up duration of 3.4 ± 2.4 years. Majority had the non-lean T2DM phenotype (40.4%), followed by non-lean non-T2DM (29.8%), lean non-T2DM (15.9%), and lean T2DM (13.9%). In the T2DM group, one-quarter was lean ( N  = 1324), while the vast majority (74.5%) was non-lean. Individuals with lean T2DM tended to be female and older. Patients with lean T2DM had the highest rates of heart failure (23.3%, p  < 0.001), cardiogenic shock (9.1%, p  = 0.036), and long-term all-cause mortality (32.6%, p  < 0.001). Cox regression demonstrated that lean T2DM was an independent predictor of mortality (adjusted hazard ratio [aHR] 1.171, 95% CI 1.040–1.319, p  = 0.009) after adjustment. The presence of higher mortality risk following AMI was present in males (aHR 1.201, 95% CI 1.037–1.391, p  = 0.015), but not in females (aHR 1.066, 95% CI 0.869–1.308, p  = 0.538). Conclusions The lean T2DM phenotype was present in one-quarter of the AMI cohort with T2DM. The lean T2DM phenotype was an independent predictor of long-term mortality following AMI, although this association was stronger in males than in females.

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.

An increasing proportion of patients with acute myocardial infarction (AMI) are presenting without standard modifiable risk factors (SMuRFs) of hypertension, hypercholesterolemia, diabetes, and smoking, but with an unexpectedly increased mortality. This study examined the SMuRF-less patients presenting with AMI in a multiethnic Asian population. We recruited patients presenting with AMI from 2011 to 2021 and compared the prevalence, clinical characteristics, and outcomes of SMuRF-less and SMuRF patients. Multivariable analysis was used to compare the outcomes of 30-day cardiovascular mortality, all-cause mortality, readmission, cardiogenic shock, stroke, and heart failure. Kaplan-Meier curves were constructed for 30-day cardiovascular mortality, with stratification by ethnicity, gender and AMI type, and 10-year all-cause mortality. Standard modifiable risk factor-less patients, who made up 8.6% of 8,680 patients, were significantly younger with fewer comorbidities that include stroke and chronic kidney disease, but higher rates of ventricular arrhythmias and inotropic or invasive ventilation requirement. Multivariable analysis showed higher rates of cardiovascular mortality (HR 1.48, 95% CI: 1.09-1.86, = 0.048), cardiogenic shock (RR: 1.31, 95% CI: 1.09-1.52, = 0.015), and stroke (RR: 2.51, 95% CI: 1.67-3.34, = 0.030) among SMuRF-less patients. A 30-day cardiovascular mortality was raised in the SMuRF-less group, with similar trends in men, patients with ST-segment elevation myocardial infarction (STEMI), and the three Asian ethnicities. All-cause mortality remains increased in the SMuRF-less group for up to 5 years. There is a significant proportion of patients with AMI without standard risk factors in Asia, who have worse short-term mortality. This calls for greater focus on the management of this unexpectedly high-risk subgroup of patients.

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.

Data are emerging on 10-year mortality comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with stenting for multivessel disease (MVD) without left main (LM) involvement. We conducted an updated two-stage meta-analysis using reconstructed individual patient data to compare long-term mortality between CABG and PCI for patients with MVD without significant LM coronary disease. Medline and Embase databases were searched for articles comparing CABG with PCI for MVD. A two-stage meta-analysis was conducted using reconstructed patient level survival data for all-cause mortality with subgroups by SYNTAX score. The shared-frailty and stratified Cox models were fitted to compare survival endpoints. We screened 1,496 studies and included six randomized controlled trials with 7,181 patients. PCI was associated with greater 10-year all-cause mortality risk (HR: 1.282, CI: 1.118-1.469, < 0.001) compared with CABG. In patients with low SYNTAX score, 10-year all-cause mortality after PCI was comparable to CABG (HR: 1.102, 0.822-1.479, = 0.516). However, in patients with moderate to high SYNTAX score, 10-year all-cause mortality was significantly higher after PCI compared with CABG (HR: 1.444, 1.122-1.858, < 0.001; HR: 1.856, 1.380-2.497, < 0.001, respectively). This updated reconstructed individual patient-data meta-analysis revealed a sustained lower cumulative all-cause mortality of CABG over PCI for multivessel disease without LM involvement.

Background: Infectious control measures during the COVID-19 pandemic have led to the propensity toward telemedicine. This study examined the impact of telemedicine during the pandemic on the long-term outcomes of ST-segment elevation myocardial infarction (STEMI) patients. Methods: This study included 288 patients admitted 1 year before the pandemic (October 2018–December 2018) and during the pandemic (January 2020–March 2020) eras, and survived their index STEMI admission. The follow-up period was 1 year. One-year primary safety endpoint was all-cause mortality. Secondary safety endpoints were cardiac readmissions for unplanned revascularisation, non-fatal myocardial infarction, heart failure, arrythmia, unstable angina. Major adverse cardiovascular events (MACE) was defined as the composite outcome of each individual safety endpoint. Results: Despite unfavorable in-hospital outcomes among patients admitted during the pandemic compared to pre-pandemic era, both groups had similar 1-year all-cause mortality (11.2 vs. 8.5%, respectively, p = 0.454) but higher cardiac-related (14.1 vs. 5.1%, p < 0.001) and heart failure readmissions in the pandemic vs. pre-pandemic groups (7.1 vs. 1.7%, p = 0.037). Follow-up was more frequently conducted via teleconsultations (1.2 vs. 0.2 per patient/year, p = 0.001), with reduction in physical consultations (2.1 vs. 2.6 per patient/year, p = 0.043), during the pandemic vs. pre-pandemic era. Majority achieved guideline-directed medical therapy (GDMT) during pandemic vs. pre-pandemic era (75.9 vs. 61.6%, p = 0.010). Multivariable Cox regression demonstrated achieving medication target doses (HR 0.387, 95% CI 0.164–0.915, p = 0.031) and GDMT (HR 0.271, 95% CI 0.134–0.548, p < 0.001) were independent predictors of lower 1-year MACE after adjustment. Conclusion: The pandemic has led to the wider application of teleconsultation, with increased adherence to GDMT, enhanced medication target dosing. Achieving GDMT was associated with favorable long-term prognosis.

Statins (3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitors) are known to reduce mortality and cardiac events in patients with coronary artery disease who have not progressed to left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). This study investigated the effect of changes in statin therapy and cholesterol level on mortality in patients with LVSD. Data from consecutive patients with LVSD enrolled in a single local hospital HF management program were analyzed. Patients were grouped according to changes in statin treatment within 4 months after their initial visit: groups NS (no statin), IS (initiation of statin), CS (continuation of statin), and SS (statin stopped). Nine hundred patients were followed for a median of 36 (28-43) months (range, 16-66 months). The 2-year mortality was 16.7%. Groups IS and CS had lower 2-year mortality than groups NS and SS (11.0% and 11.9% vs 22.0% and 34.8%, respectively; P < .001). This was independent of age, sex, severity of LVSD, HF medications, New York Heart Association functional class, and baseline cholesterol. The effect was mainly observed in patients with coronary artery disease. In 734 patients who had completed 1-year follow-up on stable HF treatment, neither baseline cholesterol nor change over 1 year predicted outcome. Initiation and maintenance of treatment with statins is associated with better survival in patients with LVSD. This could not be explained by other measured variables.

Although most of the current evidence on myocardial infarction focuses on obesity, there is growing evidence that patients who are underweight have unfavorable prognosis. This study aimed to explore the prevalence, clinical characteristics, and prognosis of this population at risk. Embase and Medline were searched for studies reporting outcomes in populations who were underweight with myocardial infarction. Underweight and normal weight were defined according to the World Health Organization criteria. A single-arm meta-analysis of proportions was used to estimate the prevalence of underweight in patients with myocardial infarction, whereas a meta-analysis of proportions was used to estimate the odds ratio of all-cause mortality, medications prescribed, and cardiovascular outcomes. Twenty-one studies involving 6,368,225 patients were included, of whom 47,866 were underweight. The prevalence of underweight in patients with myocardial infarction was 2.96% (95% confidence interval 1.96% to 4.47%). Despite having fewer classical cardiovascular risk factors, patients who were underweight had 66% greater hazard for mortality (hazard ratio 1.66, 95% confidence interval 1.44 to 1.92, p <0.0001). The mortality of patients who were underweight increased from 14.1% at 30 days to 52.6% at 5 years. Nevertheless, they were less likely to receive guideline-directed medical therapy. Relative to subjects with normal weight, Asian populations who were underweight had greater mortality risks than those of their Caucasian counterparts (p = 0.0062). In conclusion, in patients with myocardial infarction, those who were underweight tend to have poorer prognostic outcomes. A lower body mass index is an independent predictor of mortality, which calls for global efforts in addressing this modifiable risk factor in clinical practice guidelines.