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Background: Cardiogenic shock (CS) complicating myocardial infarction is associated with poor outcomes. Data among Asian populations are scarce. We aimed to investigate the long-term outcomes, prognostic factors, and predictors of CS among Asian ST elevation myocardial infarction (STEMI) patients. Methods: This was a retrospective cohort study of consecutive patients undergoing primary percutaneous coronary intervention (PPCI) for STEMI within our regional STEMI network between 2015 and 2019. The long-term outcomes of those with and without CS were compared. Clinical predictors of outcomes and development of CS were investigated. Results: A total of 1791 patients who underwent PPCI were included. Patients completed at least 2 years’ follow-up with a median follow-up period of 2.6 years (IQR 1.0, 3,9). Overall, 208/1791 (11.6 %) STEMI patients developed CS. These patients were older (61.1 ± 12.5 vs 57.8 ± 12.2, P

Summary: Background: Given the rapidly growing burden of cardiovascular disease (CVD) in Asia, this study forecasts the CVD burden and associated risk factors in Asia from 2025 to 2050. Methods: Data from the Global Burden of Disease 2019 study was used to construct regression models predicting prevalence, mortality, and disability-adjusted life years (DALYs) attributed to CVD and risk factors in Asia in the coming decades. Findings: Between 2025 and 2050, crude cardiovascular mortality is expected to rise 91.2% despite a 23.0% decrease in the age-standardised cardiovascular mortality rate (ASMR). Ischaemic heart disease (115 deaths per 100,000 population) and stroke (63 deaths per 100,000 population) will remain leading drivers of ASMR in 2050. Central Asia will have the highest ASMR (676 deaths per 100,000 population), more than three-fold that of Asia overall (186 deaths per 100,000 population), while high-income Asia sub-regions will incur an ASMR of 22 deaths per 100,000 in 2050. High systolic blood pressure will contribute the highest ASMR throughout Asia (105 deaths per 100,000 population), except in Central Asia where high fasting plasma glucose will dominate (546 deaths per 100,000 population). Interpretation: This forecast forewarns an almost doubling in crude cardiovascular mortality by 2050 in Asia, with marked heterogeneity across sub-regions. Atherosclerotic diseases will continue to dominate, while high systolic blood pressure will be the leading risk factor. Funding: This was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03), National Medical Research Council Research Training Fellowship (MH 095:003/008-303), National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Fellowship Scheme, NUHS Clinician Scientist Program (NCSP2.0/2024/NUHS/NCWS) and the CArdiovascular DiseasE National Collaborative Enterprise (CADENCE) National Clinical Translational Program (MOH-001277-01).

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.

Objective: Right-sided cardiac thrombus is rare and may be caused by venous thromboembolism, in association with medical devices or stasis of blood in atrial fibrillation (AF) and cardiomyopathies. Complications include pulmonary embolism (PE) and paradoxical stroke. Current data are limited and mostly from case series and PE registries. We aimed to describe the clinical characteristics, echocardiographic features, treatments, and outcomes of right-sided cardiac thrombus patients. Methods: This was a retrospective observational study of 97 consecutive patients with right-sided cardiac thrombus detected on echocardiography. We studied co-morbidities, predisposing factors, thrombus characteristics, and therapeutic interventions and assessed their associations with the development of PE, paradoxical stroke, circulatory collapse, and all-cause mortality. Results: The mean age was 58.7 years, and 55/97 (56.7%) of the participants were female. Ischemic heart disease (IHD), heart failure, chronic kidney disease, and malignancy were common co-morbidities. Right atrial (RA) thrombus was often associated with medical devices, while right ventricular (RV) thrombus was more commonly associated with cardiomyopathy. Thrombus mobility did not affect embolic events but was associated with greater short-term mortality. On multivariable analysis, anticoagulation (HR 0.25, 95% CI 0.09–0.68) and thrombus resolution (HR 0.28, 95% CI 0.13–0.62) were associated with greater survival. Conclusion: Right-sided cardiac thrombus is rare but may have potentially life-threatening complications such as PE and paradoxical stroke. Further research is needed to determine the optimal therapeutic strategies for this poorly studied population.

Introduction: The burden of cognitive impairment in heart failure (HF) patients is significant and leads to longer hospital stay, higher readmission rates, and increased mortality. This review seeks to synthesize the available studies to determine the prevalence and incidence of cognitive impairment and dementia in HF patients. Methods: PubMed, Embase, PsychoINFO, and Cochrane databases were systematically searched from their inception through to May 3, 2021. Study and population characteristics, total patients with HF, prevalence of cognitive impairment and dementia in HF patients, and cognitive assessment tool were abstracted by two reviewers. Results: In HF patients, the overall prevalence for cognitive impairment and dementia was 41.42% (CI) and 19.79% (dementia), respectively. We performed a meta-regression analysis, which demonstrated that the risk of cognitive impairment and dementia increased with age. Discussion: Further research should investigate whether HF accelerates the rate of cognitive decline and the progression of dementia.

BackgroundPatients suffering from acute myocardial infarction (AMI) are at risk of secondary outcomes including major adverse cardiovascular events (MACE) and heart failure (HF). Comprehensive molecular phenotyping and cardiac imaging during the post-discharge time window may provide cues for risk stratification for the outcomes.Materials and methodsIn a prospective AMI cohort in New Zealand (N = 464), we measured plasma proteins and lipids 30 days after hospital discharge and inferred a unified partial correlation network with echocardiographic variables and established clinical biomarkers (creatinine, c-reactive protein, cardiac troponin I and natriuretic peptides). Using a network-based data integration approach (iOmicsPASS+), we identified predictive signatures of long-term secondary outcomes based on plasma protein, lipid, imaging markers and clinical biomarkers and assessed the prognostic potential in an independent cohort from Singapore (N = 190).ResultsThe post-discharge levels of plasma proteins and lipids showed strong correlations within each molecular type, reflecting concerted homeostatic regulation after primary MI events. However, the two molecular types were largely independent with distinct correlation structures with established prognostic imaging parameters and clinical biomarkers. To deal with massively correlated predictive features, we used iOmicsPASS + to identify subnetwork signatures of 211 and 189 data features (nodes) predictive of MACE and HF events, respectively (160 overlapping). The predictive features were primarily imaging parameters, including left ventricular and atrial parameters, tissue Doppler parameters, and proteins involved in extracellular matrix (ECM) organization, cell differentiation, chemotaxis, and inflammation. The network signatures contained plasma protein pairs with area-under-the-curve (AUC) values up to 0.74 for HF prediction in the validation cohort, but the pair of NT-proBNP and fibulin-3 (EFEMP1) was the best predictor (AUC = 0.80). This suggests that there were a handful of plasma proteins with mechanistic and functional roles in predisposing patients to the secondary outcomes, although they may be weaker prognostic markers than natriuretic peptides individually. Among those, the diastolic function parameter (E/e' - an indicator of left ventricular filling pressure) and two ECM proteins, EFEMP1 and follistatin-like 3 (FSTL3) showed comparable performance to NT-proBNP and outperformed left ventricular measures as benchmark prognostic factors for post-MI HF.ConclusionPost-discharge levels of E/e', EFEMP1 and FSTL3 are promising complementary markers of secondary adverse outcomes in AMI patients.

Summary: Background: Malnutrition and obesity are interdependent pathologies along the same spectrum. We examined global trends and projections of disability-adjusted life years (DALYs) and deaths from malnutrition and obesity until 2030. Methods: Using data from the 2019 Global Burden of Disease study involving 204 countries and territories, trends in DALYs and deaths were described for obesity and malnutrition from 2000 to 2019, stratified by geographical regions (as defined by WHO) and Socio-Demographic Index (SDI). Malnutrition was defined according to the 10th revision of International Classification of Diseases codes for nutritional deficiencies, stratified by malnutrition type. Obesity was measured via body mass index (BMI) using metrics related to national and subnational estimates, defined as BMI ≥25 kg/m2. Countries were stratified into low, low-middle, middle, high-middle, and high SDI bands. Regression models were constructed to predict DALYs and mortality up to 2030. Association between age-standardised prevalence of the diseases and mortality was also assessed. Findings: In 2019, age-standardised malnutrition-related DALYs was 680 (95% UI: 507–895) per 100,000 population. DALY rates decreased from 2000 to 2019 (−2.86% annually), projected to fall 8.4% from 2020 to 2030. Africa and low SDI countries observed highest malnutrition-related DALYs. Age-standardised obesity-related DALY estimates were 1933 (95% UI: 1277–2640). Obesity-related DALYs rose 0.48% annually from 2000 to 2019, predicted to increase by 39.8% from 2020 to 2030. Highest obesity-related DALYs were in Eastern Mediterranean and middle SDI countries. Interpretation: The ever-increasing obesity burden, on the backdrop of curbing the malnutrition burden, is predicted to rise further. Funding: None.

Resumo A produção de ceramida ocorre em todo o corpo e desempenha um papel importante na manutenção da fisiologia normal. No entanto, os níveis de ceramidas são alterados em estados de doença, principalmente durante o desenvolvimento de diabetes e dislipidemia. A produção de ceramidas também está associada à instabilidade das placas ateroscleróticas. Estudos recentes revelam que pacientes com doença arterial coronariana instável apresentam níveis plasmáticos aumentados de ceramidas (principalmente C16, C18 e C24:1). Atualmente, são consideradas biomarcadores emergentes nas doenças cardiovasculares, sendo utilizadas na predição de instabilidade da placa aterosclerótica e eventos cardiovasculares adversos de forma independente aos fatores de risco tradicionais. Com o objetivo de descrever e discutir o papel das ceramidas na estratificação das doenças cardiovasculares, o desenvolvimento desta revisão narrativa contextualiza a importância desse biomarcador no cenário atual da cardiologia.

Bleeding complications limits the use of effective antithrombotics therapeutics. Here, the authors developed next-generation direct thrombin inhibitors with low bleeding risks as safe peri-percutaneous coronary intervention anticoagulants when used in combination with antiplatelets.

Abstract Patients with cancer are at increased risk of myocardial infarction (MI) and stroke. Guidelines do not address lipid profile targets for these patients. Within the lipid profiles, we hypothesized that patients with cancer develop MI or stroke at lower low density lipoprotein cholesterol (LDL-C) concentrations than patients without cancer and suffer worse outcomes. We linked nationwide longitudinal MI, stroke and cancer registries from years 2007–2017. We identified 42,148 eligible patients with MI (2421 prior cancer; 39,727 no cancer) and 43,888 eligible patients with stroke (3152 prior cancer; 40,738 no cancer). Median LDL-C concentration was lower in the prior cancer group than the no cancer group at incident MI [2.43 versus 3.10 mmol/L, adjusted ratio 0.87 (95% CI 0.85–0.89)] and stroke [2.81 versus 3.22 mmol/L, adjusted ratio 0.93, 95% CI 0.91–0.95)]. Similarly, median triglyceride and total cholesterol concentrations were lower in the prior cancer group, with no difference in high density lipoprotein cholesterol. Prior cancer was associated with higher post-MI mortality [adjusted hazard ratio (HR) 1.48, 95% CI 1.37–1.59] and post-stroke mortality (adjusted HR 1.95, 95% CI 1.52–2.52). Despite lower LDL-C concentrations, patients with prior cancer had worse post-MI and stroke mortality than patients without cancer.

IntroductionCoagulation is involved in fibroproliferative responses following acute myocardial infarction (AMI). Left ventricular (LV) remodeling following AMI is closely associated with progression to heart failure. This study aims to assess the association between plasma tissue factor activity and LV remodeling in post-AMI patients.MethodsWe studied 228 patients with AMI and 57 healthy subjects. Patients with AMI were categorized into two age- and sex-matched groups: patients with adverse LV remodeling or reverse LV remodeling, defined by an increase or decrease, respectively, in LV end systolic volume by ≥15% over 6 months. TF activity was measured in plasma collected at baseline (within 72 hours of revascularization), 1 month and 6 months post-AMI. Multiple level longitudinal data analysis with structural equation (ML-SEM) model was used to assess the impact of various clinical variables on TF activity in post-AMI.ResultsPlasma TF activity in post-AMI patients at baseline (29.05 ± 10.75 pM) was similar to that in healthy subjects but fell at 1 month (21.78 ± 8.23, p

Cognitive impairment (CI) shares common cardiovascular risk factors with acute myocardial infarction (AMI), and is increasingly prevalent in our ageing population. Whilst AMI is associated with increased rates of CI, CI remains underreported and infrequently identified in patients with AMI. In this review, we discuss the evidence surrounding AMI and its links to dementia and CI, including pathophysiology, risk factors, management and interventions. Vascular dysregulation plays a major role in CI, with atherosclerosis, platelet activation, microinfarcts and perivascular inflammation resulting in neurovascular unit dysfunction, disordered homeostasis and a dysfunctional neurohormonal response. This subsequently affects perfusion pressure, resulting in enlarged periventricular spaces and hippocampal sclerosis. The increased platelet activation seen in coronary artery disease (CAD) can also result in inflammation and amyloid-β protein deposition which is associated with Alzheimer’s Dementia. Post-AMI, reduced blood pressure and reduced left ventricular ejection fraction can cause chronic cerebral hypoperfusion, cerebral infarction and failure of normal circulatory autoregulatory mechanisms. Patients who undergo coronary revascularization (percutaneous coronary intervention or bypass surgery) are at increased risk for post-procedure cognitive impairment, though whether this is related to the intervention itself or underlying cardiovascular risk factors is debated. Mortality rates are higher in dementia patients with AMI, and post-AMI CI is more prevalent in the elderly and in patients with post-AMI heart failure. Medical management (antiplatelet, statin, renin-angiotensin system inhibitors, cardiac rehabilitation) can reduce the risk of post-AMI CI; however, beta-blockers may be associated with functional decline in patients with existing CI. The early identification of those with dementia or CI who present with AMI is important, as subsequent tailoring of management strategies can potentially improve outcomes as well as guide prognosis.

Abstract Background Cardiovascular magnetic resonance (CMR) sequences are commonly used to obtain a complete description of the function and structure of the heart, provided that accurate measurements are extracted from images. New methods of extraction of information are being developed, among them, deep neural networks are powerful tools that showed the ability to perform fast and accurate segmentation. Iq1n order to reduce the time spent by reading physicians to process data and minimize intra- and inter-observer variability, we propose a fully automatic multi-scan CMR image analysis pipeline. Methods Sequence specific U-Net 2D models were trained to perform the segmentation of the left ventricle (LV), right ventricle (RV) and aorta in cine short-axis, late gadolinium enhancement (LGE), native T1 map, post-contrast T1, native T2 map and aortic flow sequences depending on the need. The models were trained and tested on a set of data manually segmented by experts using semi-automatic and manual tools. A set of parameters were computed from the resulting segmentations such as the left ventricular and right ventricular ejection fraction (EF), LGE scar percentage, the mean T1, T1 post, T2 values within the myocardium, and aortic flow. The Dice similarity coefficient, Hausdorff distance, mean surface distance, and Pearson correlation coefficient R were used to assess and compare the results of the U-Net based pipeline with intra-observer variability. Additionally, the pipeline was validated on two clinical studies. Results The sequence specific U-Net 2D models trained achieved fast (≤ 0.2 s/image on GPU) and precise segmentation over all the targeted region of interest with high Dice scores (= 0.91 for LV, = 0.92 for RV, = 0.93 for Aorta in average) comparable to intra-observer Dice scores (= 0.86 for LV, = 0.87 for RV, = 0.95 for aorta flow in average). The automatically and manually computed parameters were highly correlated (R = 0.91 in average) showing results superior to the intra-observer variability (R = 0.85 in average) for every sequence presented here. Conclusion The proposed pipeline allows for fast and robust analysis of large CMR studies while guaranteeing reproducibility, hence potentially improving patient’s diagnosis as well as clinical studies outcome.

(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.

Abstract Background Little is known about the impact of the global coronavirus disease-2019 (COVID-19) pandemic on patients with cardiovascular disease (CVD), the biggest global killer and major risk factor for severe COVID-19 infections. We aim to explore the indirect consequences of COVID-19 on health-related quality of life (HRQoL) of patients with CVD. Methods Eighty-one adult outpatients with CVD were assessed using the EQ-5D, a generic health status instrument with five dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), before and during the pandemic. Changes in the EQ-5D dimensional responses were compared categorically as well as using the dimension-specific sum-score (range 1–3, with a higher score indicating worse health). The responses and sum-score were compared using the exact test of symmetry and the paired t-test, respectively. Results These patients [mean age (SD) 59.8 (10.5); 92.6% males; 56% New York Heart Association (NYHA) functional class I] had coronary artery disease (69%), heart failure (28%), or arrhythmias (15%). None experienced change in NYHA class between assessments. About 30% and 38% of patients reported problems with at least one of the EQ-5D dimensions pre-pandemic and during the pandemic, respectively. The highest increase in health problems was reported for anxiety/depression (12.5% pre-pandemic vs 23.5% during pandemic; p = 0.035) with mean domain-specific score from 1.12 (SD 0.33) to 1.25 (SD 0.46) (standardized effect size = 0.373, p = 0.012). There was no meaningful change in other dimensions as well as overall HRQoL. Conclusion The COVID-19 pandemic is associated with a significant worsening of the mental health of patients with CVD.

Objectives: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce serum urate in patients with type 2 diabetes mellitus. To evaluate if this effect applies to both patients with and without diabetes, we conducted a systematic review and meta-analysis of SGLT2 inhibitors on serum urate levels in this population. Methods: Four electronic databases (PubMed, Embase, Cochrane and SCOPUS) were searched on 25 September 2021 for articles published from 1 January 2000 up to 25 September 2021, for studies that examined the effect of SGLT2 inhibitors on serum urate in study subjects. Random-effects meta-analysis was performed, with subgroup analyses on the type of SGLT2 inhibitor agent administered, presence of type 2 diabetes mellitus, presence of chronic kidney disease and drug dose. Results: A total of 43 randomized controlled trials, with a combined cohort of 31,921 patients, were included. Both patients with [−31.48 μmol/L; 95% confidence interval (CI): −37.35 to −25.60] and without diabetes (−91.38 μmol/L; 95% CI: −126.53 to −56.24) on SGLT2 inhibitors had significantly lower urate levels when compared with placebo. This treatment effect was similarly observed across different types of SGLT2 inhibitors. However, in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease, the reduction in serum urate with SGLT2 inhibitors became insignificant (95% CI: −22.17 to 5.94, p

Targeted mass spectrometry enables reproducible and accurate lipid quantification but dedicated software tools to develop targeted lipidomics assays are lacking. Here, the authors develop a targeted lipidomics workbench and lipid knowledgebase for the streamlined generation of targeted assays.

Quantitative MS of human plasma lipids is a promising technology for translation into clinical applications. Current MS-based lipidomic methods rely on either direct infusion (DI) or chromatographic lipid separation methods (including reversed phase and hydrophilic interaction LC). However, the use of lipid markers in laboratory medicine is limited by the lack of reference values, largely because of considerable differences in the concentrations measured by different laboratories worldwide. These inconsistencies can be explained by the use of different sample preparation protocols, method-specific calibration procedures, and other experimental and data-reporting parameters, even when using identical starting materials. Here, we systematically investigated the roles of some of these variables in multiple approaches to lipid analysis of plasma samples from healthy adults by considering: 1) different sample introduction methods (separation vs. DI methods); 2) different MS instruments; and 3) between-laboratory differences in comparable analytical platforms. Each of these experimental variables resulted in different quantitative results, even with the inclusion of isotope-labeled internal standards for individual lipid classes. We demonstrated that appropriate normalization to commonly available reference samples (i.e., “shared references”) can largely correct for these systematic method-specific quantitative biases. Thus, to harmonize data in the field of lipidomics, in-house long-term references should be complemented by a commonly available shared reference sample, such as NIST SRM 1950, in the case of human plasma.

Background Post-acute coronary syndrome (ACS) depression is a common but not well understood complication experienced by ACS patients. Research on the effectiveness of various therapies remains limited. Hence, we sought to conduct a network meta-analysis to assess the efficacy of different interventions for post-ACS depression in improving patient outcomes. Methods and findings Three electronic databases were searched for randomised controlled trials describing different depression treatment modalities in post-ACS patients. Each article was screened based on inclusion criteria and relevant data were extracted. A bivariate analysis and a network meta-analysis was performed using risk ratios (RR) and standardized mean differences (SMD) for binary and continuous outcomes, respectively. A total of 30 articles were included in our analysis. Compared to standard care, psychosocial therapy was associated with the greatest reduction in depression scores (SMD:-1.21, 95% CI: -1.81 to -0.61, pConclusion This network meta-analysis found that the treatment effect of the various psychological modalities on depression severity were similar. Future trials on psychological interventions assessing clinical outcomes and improvement in adherence to ACS-specific interventions are needed.

The subset of plasma extracellular vesicles (EVs) that coprecipitate with low-density lipoprotein (LDL-EVs) carry coagulation and fibrinolysis pathway proteins as cargo. We investigated the association between LDL-EV hemostatic/fibrinolysis protein ratios and post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling which precedes heart failure. Protein concentrations of von Willebrand factor (VWF), SerpinC1 and plasminogen were determined in LDL-EVs extracted from plasma samples obtained at baseline (within 72 h post-AMI), 1 month and 6 months post-AMI from 198 patients. Patients were categorized as exhibiting adverse (n = 98) or reverse (n = 100) LV remodeling based on changes in LV end-systolic volume (increased or decreased ≥15) over a 6-month period. Multiple level longitudinal data analysis with structural equation (ML-SEM) model was used to assess predictive value for LV remodeling independent of baseline differences. At baseline, protein levels of VWF, SerpinC1 and plasminogen in LDL-EVs did not differ between patients with adverse versus reverse LV remodeling. At 1 month post-AMI, protein levels of VWF and SerpinC1 decreased whilst plasminogen increased in patients with adverse LV remodeling. In contrast, VWF and plasminogen decreased whilst SerpinC1 remained unchanged in patients with reverse LV remodeling. Overall, compared with patients with adverse LV remodeling, higher levels of SerpinC1 and VWF but lower levels of plasminogen resulted in higher ratios of VWF:Plasminogen and SerpinC1:Plasminogen at both 1 month and 6 months post-AMI in patients with reverse LV remodeling. More importantly, ratios VWF:Plasminogen (AUC = 0.674) and SerpinC1:Plasminogen (AUC = 0.712) displayed markedly better prognostic power than NT-proBNP (AUC = 0.384), troponin-I (AUC = 0.467) or troponin-T (AUC = 0.389) (p < 0.001) to predict reverse LV remodeling post-AMI. Temporal changes in the ratios of coagulation to fibrinolysis pathway proteins in LDL-EVs outperform current standard plasma biomarkers in predicting post-AMI reverse LV remodeling. Our findings may provide clinical cues to uncover the cellular mechanisms underpinning post-AMI reverse LV remodeling.

Acute myocardial infarction (AMI) is a leading cause of mortality and morbidity worldwide. This work aims to investigate the translational potential of a multi-omics study (comprising metabolomics, lipidomics, glycomics, and metallomics) in revealing biomechanistic insights into AMI. Following the N-glycomics and metallomics studies performed by our group previously, untargeted metabolomic and lipidomic profiles were generated and analysed in this work via the use of a simultaneous metabolite/lipid extraction and liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis workflow. The workflow was applied to blood plasma samples from AMI cases (n = 101) and age-matched healthy controls (n = 66). The annotated metabolomic (number of features, n = 27) and lipidomic (n = 48) profiles, along with the glycomic (n = 37) and metallomic (n = 30) profiles of the same set of AMI and healthy samples were integrated and analysed. The integration method used here works by identifying a linear combination of maximally correlated features across the four omics datasets, via utilising both block-partial least squares-discriminant analysis (block-PLS-DA) based on sparse generalised canonical correlation analysis. Based on the multi-omics mapping of biomolecular interconnections, several postulations were derived. These include the potential roles of glycerophospholipids in N-glycan-modulated immunoregulatory effects, as well as the augmentation of the importance of Ca–ATPases in cardiovascular conditions, while also suggesting contributions of phosphatidylethanolamine in their functions. Moreover, it was shown that combining the four omics datasets synergistically enhanced the classifier performance in discriminating between AMI and healthy subjects. Fresh and intriguing insights into AMI, otherwise undetected via single-omics analysis, were revealed in this multi-omics study. Taken together, we provide evidence that a multi-omics strategy may synergistically reinforce and enhance our understanding of diseases.

Background: Patients with cancer are at increased risk of acute myocardial infarction (AMI). It is unclear if the Atherosclerotic Cardiovascular Disease (ASCVD) risk score at incident AMI is reflective of this higher risk in patients with prior cancer than those without. Methods: We linked nationwide AMI and cancer registries from 2008 to 2019. A total of 18,200 eligible patients with ASCVD risk score calculated at incident AMI were identified (1086 prior cancer; 17,114 no cancer). Results: At incident AMI, age-standardized mean ASCVD risk was lower in the prior cancer group (18.6%) than no cancer group (20.9%) (p < 0.001). Prior to incident AMI, smoking, hypertension, hyperlipidemia and diabetes mellitus were better controlled in the prior cancer group. However post-AMI, prior cancer was associated with lower guideline-directed medical therapy usage and higher all-cause mortality (adjusted hazard ratio 1.85, 95% confidence interval 1.66–2.07). Conclusions: AMI occurred despite better control of cardiovascular risk factors and lower age-standardized estimated mean 10-year ASCVD risk among patients with prior cancer than no cancer. Prior cancer was associated with lower guideline-directed medical therapy post-AMI and higher mortality.

Summary: Untargeted metabolomics is used to refine the development of biomarkers for the diagnosis of cardiovascular disease. Myocardial infarction (MI) has major individual and societal consequences for patients, who remain at high risk of secondary events, despite advances in pharmacological therapy. To monitor their differential response to treatment, we performed untargeted plasma metabolomics on 175 patients from the platelet inhibition and patient outcomes (PLATO) trial treated with ticagrelor and clopidogrel, two common P2Y12 inhibitors. We identified a signature that discriminates patients, which involves polyunsaturated fatty acids (PUFAs) and particularly the omega-3 fatty acids docosahexaenoate and eicosapentaenoate. The known cardiovascular benefits of PUFAs could contribute to the efficacy of ticagrelor. Our work, beyond pointing out the high relevance of untargeted metabolomics in evaluating response to treatment, establishes PUFA metabolism as a pathway of clinical interest in the recovery path from MI.

Acute myocardial infarction (AMI) is associated with heightened thrombin generation. There are limited data relating to thrombin generation and left ventricular (LV) scarring and LV dilatation in post-MI LV remodeling. We studied 113 patients with ST-segment elevation myocardial infarction (STEMI) who had undergone primary percutaneous coronary intervention (PPCI) (n = 76) or pharmaco-invasive management (thrombolysis followed by early PCI, n = 37). Endogenous thrombin potential (ETP) was measured at baseline, 1 month and 6 months. Cardiovascular magnetic resonance imaging was performed at baseline and 6 months post-MI. Outcomes studied were an increase in scar change, which was defined as an increase in left ventricular infarct size of any magnitude detected by late gadolinium enhancement, adverse LV remodeling, defined as dilatation (increase) of left ventricular end-diastolic volume (LVEDV) by more than 20% and an increase in left ventricular ejection fraction (LVEF). The mean age was 55.19 ± 8.25 years and 91.2% were men. The baseline ETP was similar in the PPCI and pharmaco-invasive groups (1400.3 nM.min vs. 1334.1 nM.min, p = 0.473). Each 10-unit increase in baseline ETP was associated with a larger scar size (adjusted OR 1.020, 95% CI 1.002–1.037, p = 0.027). Baseline ETP was not associated with adverse LV remodeling or an increase in LVEF. There was no difference in scar size or adverse LV remodeling among patients undergoing PPCI vs. pharmaco-invasive management or patients receiving ticagrelor vs. clopidogrel. Enhanced thrombin generation after STEMI is associated with a subsequent increase in myocardial scarring but not LV dilatation or an increase in LVEF at 6 months post-MI.

Background Because of a nonresponse to aspirin (aspirin resistance), patients with acute coronary syndrome (ACS) are at increased risk of developing recurrent event. The in vitro platelet function tests have potential limitations, making them unsuitable for the detection of aspirin resistance. We investigated whether miR‐19b‐1‐5p could be utilized as a biomarker for aspirin resistance and future major adverse cardio‐cerebrovascular (MACCE) events in patients with ACS. Methods and Results In this cohort study, patients with ACS were enrolled from multiple tertiary hospitals in Christchurch, Hong Kong, Sarawak, and Singapore between 2011 and 2015. MiR‐19b‐1‐5p expression was measured from buffy coat of patients with ACS (n=945) by reverse transcription quantitative polymerase chain reaction. Platelet function was determined by Multiplate aggregometry testing. MACCE was collected over a mean follow‐up time of 1.01±0.43 years. Low miR‐19b‐1‐5p expression was found to be related to aspirin resistance as could be observed from sustained platelet aggregation in the presence of aspirin (‐Log‐miR‐19b‐1‐5p, [unstandardized beta, 44.50; 95% CI, 2.20–86.80; P

Abstract Introduction The incidence of left ventricular (LV) thrombus formation in ST-segment elevation myocardial infarction (STEMI) patients in the current era of primary percutaneous coronary intervention (PCI) is not well established. We performed a meta-analysis to assess the actual incidence and predictors of LV thrombus by cardiovascular magnetic resonance (CMR) in STEMI treated by primary PCI. Methods We searched MEDLINE and EMBASE databases up to February 2018. We included all studies published as a full-text article, reporting the incidence of LV thrombus by CMR within 1 month following acute STEMI in patients treated by primary PCI. A binary random-effects model was used to estimate the pooled incidence of LV thrombus. The diagnostic performance of transthoracic echocardiography (TTE) as compared with CMR was pooled to obtain the sensitivity and specificity of TTE with CMR as the gold standard. Embolic and bleeding complications of LV thrombus were also evaluated. Results Ten studies were included in the meta-analysis. The incidence of LV thrombus by CMR in all-comer STEMI patients (n = 2072) was 6.3% with 96% of LV thrombus occurring in those with anterior STEMI (12.2% incidence). When only anterior STEMI with LVEF

Summary: We identified a plasma signature of 11 C14 to C26 ceramides and 1 C16 dihydroceramide predictive of major adverse cardiovascular events in patients with acute myocardial infarction (AMI). Among patients undergoing coronary artery bypass surgery, those with recent AMI, compared with those without recent AMI, showed a significant increase in 5 of the signature’s 12 ceramides in plasma but not simultaneously-biopsied aortic tissue. In contrast, a rat AMI model, compared with sham control, showed a significant increase in myocardial concentrations of all 12 ceramides and up-regulation of 3 ceramide-producing enzymes, suggesting ischemic myocardium as a possible source of this ceramide signature. Key Words: acute coronary syndrome, ceramides, dihydroceramides, major adverse cardiovascular and cerebrovascular events, prognosis, risk prediction