INTRODUCTION: Elevated troponin, while essential for diagnosing myocardial infarction, can also be present in non-myocardial infarction conditions. The myocardial-ischaemic-injury-index (MI3) algorithm is a machine learning algorithm that considers age, sex and cardiac troponin I (TnI) results to risk-stratify patients for type 1 myocardial infarction. METHOD: Patients aged ≥25 years who presented to the emergency department (ED) of Singapore General Hospital with symptoms suggestive of acute coronary syndrome with no diagnostic 12-lead electrocardiogram (ECG) changes were included. Participants had serial ECGs and high-sensitivity troponin assays performed at 0, 2 and 7 hours. The primary outcome was the adjudicated diagnosis of type 1 myocardial infarction at 30 days. We compared the performance of MI3 in predicting the primary outcome with the European Society of Cardiology (ESC) 0/2-hour algorithm as well as the 99th percentile upper reference limit (URL) for TnI. RESULTS: There were 1351 patients included (66.7% male, mean age 56 years), 902 (66.8%) of whom had only 0-hour troponin results and 449 (33.2%) with serial (both 0 and 2-hour) troponin results available. MI3 ruled out type 1 myocardial infarction with a higher sensitivity (98.9, 95% confidence interval [CI] 93.4-99.9%) and similar negative predictive value (NPV) 99.8% (95% CI 98.6-100%) as compared to the ESC strategy. The 99th percentile cut-off strategy had the lowest sensitivity, specificity, positive predictive value and NPV. CONCLUSION The MI3 algorithm was accurate in risk stratifying ED patients for myocardial infarction. The 99th percentile URL cut-off was the least accurate in ruling in and out myocardial infarction compared to the other strategies.
Humans ; Male ; Female ; Emergency Service, Hospital ; Middle Aged ; Electrocardiography ; Machine Learning ; Singapore ; Chest Pain/blood* ; Troponin I/blood* ; Myocardial Infarction/blood* ; Risk Assessment/methods* ; Aged ; Algorithms ; Acute Coronary Syndrome/blood* ; Adult ; Sensitivity and Specificity

INTRODUCTION: Outcomes after SARS-CoV-2 Omicron infection in patients with heart failure (HF) and ischaemic heart disease (IHD) remain poorly defined. METHOD: In a highly vaccinated cohort of adult Singapore citizens and permanent residents, we used Cox proportional hazards models (adjusted for sociodemographic variables and comorbidities) to compare the risks of Omicron infection, COVID-19- related hospitalisation, and severe COVID-19 between indivi-duals with HF or IHD and matched controls without these conditions. RESULTS: From national databases, we identified 15,426 HF patients matched 1:∼3 to 41,221 controls, and 110,442 IHD patients matched 1:∼2 to 223,843 controls. Over 80% of HF and IHD patients had received at least 3 vaccine doses. During the Omicron-predominant period, both HF and IHD cohorts demonstrated higher adjusted risks of COVID-19 hospitalisation compared with matched controls (HF: adjusted hazard ratio [aHR] 1.77, 95% confidence interval [CI] 1.65-1.90; IHD: aHR 1.21, 95% CI 1.17-1.26). Among those with at least 1 HF-or IHD-related admission in the prior year, hospitalisation risk was further elevated (HF: aHR 1.27, 95% CI 1.13-1.42; IHD: aHR 1.11, 95% CI 1.01-1.23). Receipt of ≥3 vaccine doses was associated with substantially lower risk of severe COVID-19 versus only 2 doses (HF: aHR 0.35, 95% CI 0.28-0.43; IHD: aHR 0.27, 95% CI 0.23-0.32). A fourth dose conferred additional reductions in infection and adverse outcomes, though CIs for infection overlapped with those for 3 doses. CONCLUSION During Omicron predominance, HF and IHD patients experienced greater risk of COVID-19 hospitalisation and severe COVID-19 versus matched controls. Booster vaccinations attenuated these risks. Individuals with recent HF/IHD admissions should be prioritised for receipt of booster vaccine doses.
Humans ; COVID-19/complications* ; Male ; Heart Failure/complications* ; Myocardial Ischemia/complications* ; Female ; Middle Aged ; Hospitalization/statistics & numerical data* ; Aged ; COVID-19 Vaccines/administration & dosage* ; Singapore/epidemiology* ; SARS-CoV-2 ; Proportional Hazards Models ; Adult ; Case-Control Studies ; Vaccination/statistics & numerical data*

INTRODUCTION

While a 600 mg loading dose (LD) of clopidogrel has demonstrated superior inhibition of platelet function compared to 300 mg LD, the clinical evidence supporting this superiority is limited. The debate centers on whether higher clopidogrel LD regimen in percutaneous coronary intervention (PCI) outperforms the standard 300 mg LD, with potential benefits being more pronounced in higher-risk patients. Balancing enhanced platelet inhibition to reduce ischemic events against the associated risk of increased bleeding remains a critical consideration in determining the optimal loading dose of clopidogrel for patients with ischemic heart disease.

A systematic literature search for randomized clinical trials (RCTs) was performed comparing 600 mg with 300 mg LD of clopidogrel using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov and HerdinPH. Studies included those between 2010 and 2023 involving human subjects. The primary efficacy endpoint was a 1-month rate of major adverse cardiac event (MACE) and the primary safety outcome was bleeding adverse effects.

Nine RCTs involving 29,827 patients were included in the efficacy analysis. Mean duration of follow-up was 30 days. Only eight studies were eligible for safety analysis. Compared with standard LD clopidogrel, high LD significantly reduced the incidence of overall MACE (OR: 0.82, 95% CI: 0.74-0.91, p = 0.0002), nonfatal myocardial infarction (OR: 0.56; 95% CI: 0.32-0.99, p = 0.15) and target vessel revascularization (OR: 0.63; 95% CI: 0.41-0.95, p = 0.03), without significant difference in terms of cardiac death (OR: 0.89; 95% CI: 0.76-1.04, p = 0.15) and stroke (OR: 0.92; 95% CI: 0.67-1.26, p = 0.61). However, major bleeding risk was higher in the 600 mg LD (1.9%; 261/13288) compared with 300 mg LD (2.4%; 328/13242) [OR: 1.27; 95% CI: 1.08-1.49, p = 0.005] without significant difference in minor bleeding (OR: 1.05; 95% CI: 0.94-1.17, p = 0.35).

The administration of 600 mg clopidogrel LD reduces the overall risk of MACE with associated increased risk of major bleeding.

BACKGROUND

Postoperative atrial fibrillation (POAF) is the most common arrythmia to occur after cardiovascular surgery. Inflammation being pivotal in POAF perpetuation has been utilized as a therapeutic target. Owing to their anti-inflammatory and anti-oxidant effects, beta-blockers (BB) and N-acetylcysteine (NAC) became research interests in the pursuit for an effective POAF prevention strategy.

To determine the efficacy of NAC plus BB versus BB alone in preventing POAF in cardiac surgery patients.

A literature search using the following search engines: PubMed/Medline, Cochrane Review Central, Clinical Trials Registry, ResearchGate, Mendeley and Google Scholar for relevant randomized trials were conducted. Published and unpublished studies indexed from inception until 2023 were included. Three independent reviewers evaluated the randomized clinical trials (RCTs) for eligibility. The pooled estimates for POAF prevention as primary outcome and MACE, mortality, myocardial infarction, stroke, ICU LOS and hospital LOS as secondary outcomes were measured using the RStudio statistical software.

Seven eligible RCTs allocated 1069 cardiac surgery patients to NAC + BB (n=539) and BB alone (N = 530) treatment arms. The effect estimate using random effect model disclosed significantly reduced POAF events (RR 0.62, 95% CI [0.44, 0.86], p = 0.005) in those on NAC + BB. While no statistical difference between the study arms were demonstrated in reducing mortality (RR 0.63, 95% CI [0.23, 1.73], p = 0.37); myocardial infarction (RR 1.02, 95% CI [0.49, 2.13], p = 0.96); stroke (RR 0.95, 95% CI [0.24, 3.68], p = 0.94); ICU LOS (std. mean difference 0.14, 95% CI [-0.43, 0.70], p = 0.41), and hospital LOS (std. mean difference 0.08, 95% CI [-0.06, 0.21], p = 0.19).

Among cardiac surgery patients, the use of NAC in combination with BB compared with BB alone significantly reduced POAF.

BACKGROUND

Chest pain is a common reason for emergency room visits. The HEART score is used as a risk stratification tool to aid in clinical decision making. The HEART score is a useful tool due to its good sensitivity, however it has low specificity. The SVEAT score was developed as an improved risk stratification tool which outperformed the HEART score in previous studies. Both the performance of HEART and SVEAT scores lack data in our locality.

To compare the performance of Symptoms, Vascular disease, Electrocardiography, Age, Troponin-I (SVEAT) score and History, Electrocardiography, Age, Risk factors, Troponin-I (HEART) score as predictors of in-hospital Major Adverse Cardiovascular Events (MACE) among adult patients admitted in Chong Hua Hospital Cebu for chest pain.

This single-center, retrospective, observational analytic study included adult patients, ages 18 years old and above, who were admitted for chest pain from January 1, 2022 to December 31, 2022. All patients who passed the inclusion and exclusion criteria were included in the data analysis. Both SVEAT and HEART scores were calculated for each of the included subjects. The performance of both scoring criteria was compared using logistic regression and area under the receiving-operator characteristic curve.

A total of 113 cases were analyzed after exclusion criteria were applied. A total of 50 (44.2%) individuals suffered MACE. The difference in AUC of both SVEAT (0.946, 95%CI) and HEART (0.936, 95%CI) was not statistically significant (95% CI – 0.013 – 0.033, p = 0.400). With a cut-off ofCONCLUSION

SVEAT and HEART scores had similar performance in predicting in hospital MACE. Using a cut-off value of
Human ; Chest Pain ; Heart ; Myocardial Infarction ; Acute Coronary Syndrome

We describe an unusual case of hypoxic ischemic encephalopathy in a preterm female of 36 weeks who presented with status epilepticus and atypical abdominal myoclonus. The seizures were confirmed electrographically using video electroencephalography (EEG), while the abdominal myoclonus was demonstrated to be nonepileptic, as it had no EEG correlate. Other possible causes of neonatal seizures were excluded. The infant then responded to a gamut of antiseizure medications but the myoclonus persisted. To the best of our knowledge, this is the first report of atypical myoclonus in a preterm baby caused by hypoxic ischemic encephalopathy.

INTRODUCTION: Arrhythmias, especially atrial fibrillation (AF) and ventricular arrhythmias, are independent risk factors of mortality in patients with ischaemic heart disease (IHD). While there is a growing body of evidence that suggests an association between obstructive sleep apnoea (OSA) and cardiac arrhythmias, evidence on this relationship in patients with IHD has been scant and inconsistent. We hypothesised that in patients with IHD, severe OSA is associated with an increased risk of nocturnal arrhythmias. METHODS: We studied 103 consecutive patients with IHD who underwent an overnight polysomnography. Exposed subjects were defined as patients who had an apnoea-hypopnoea index (AHI) ≥30/h (severe OSA), and nonexposed subjects were defined as patients who had an AHI <30/h (nonsevere OSA). All electrocardiograms (ECGs) were interpreted by the Somte ECG analysis software and confirmed by a physician blinded to the presence or absence of exposure. Arrhythmias were categorised as supraventricular and ventricular. Arrhythmia subtypes (ventricular, atrial and conduction delay) were analysed as dichotomous outcomes using multiple logistic regression models. RESULTS: Atrial fibrillation and AF/flutter (odds ratio 13.5, 95% confidence interval 1.66-109.83; P = 0.003) were found to be more common in the severe OSA group than in the nonsevere OSA group. This association remained significant after adjustment for potential confounders. There was no significant difference in the prevalence of ventricular and conduction delay arrhythmias between the two groups. CONCLUSION In patients with IHD, there was a significant association between severe OSA and nocturnal AF/flutter. This underscores the need to evaluate for OSA in patients with IHD, as it may have important implications on clinical outcomes.
Humans ; Sleep Apnea, Obstructive/diagnosis* ; Atrial Fibrillation/diagnosis* ; Male ; Female ; Middle Aged ; Polysomnography ; Electrocardiography ; Myocardial Ischemia/complications* ; Aged ; Risk Factors ; Logistic Models

INTRODUCTION: Achieving low-density lipoprotein cholesterol (LDL-C) levels is key to preventing atherosclerotic cardiovascular events. However, many high-risk cardiovascular patients still experience poor LDL-C goal attainment and receive suboptimal lipid-lowering therapy (LLT) prescriptions. Herein, we evaluated LLT prescription patterns, LDL-C goal attainment and cardiovascular mortality among this population group in Singapore. METHODS: This prospective observational cohort study included 555 patients with ischaemic heart disease (IHD) admitted to the hospital in 2020. The LLT prescriptions, corresponding LDL-C levels and cardiovascular outcomes were assessed over a 24-month period. RESULTS: Most participants were male (82.3%), with 48.5% identified as Chinese. High-intensity statin prescriptions increased from 45.4% at hospital admission to 87.1% at discharge and remained stable at approximately 80% at 6, 12, and 24 months post-discharge. Combination LLT prescriptions increased from 12.3% at discharge to 33.8% by 24 months. Ezetimibe was the most commonly prescribed second-line LLT (40.8%), followed by inclisiran (1.09%) and anti-proprotein convertase subtilisin/kexin type 9 monoclonal antibody therapies (0.87%). Over 24 months, LDL-C goal attainment rates were 22.1% for LDL-C < 1.4 mmol/L and 47.2% for LDL-C < 1.8 mmol/L. Multivariable Cox proportional hazards regression indicated that achieving LDL-C < 1.8 mmol/L goal was associated with a reduction in all-cause mortality at 24 months (hazard ratio 0.53, 95% confidence interval 0.30-0.94, P = 0.030). CONCLUSION Treatment gaps in lipid management persist in 80% of the study population, indicating that statin monotherapy alone is insufficient to achieve LDL-C goals. Greater efforts to improve LDL-C goal attainment rates in high-risk cardiovascular patients are imperative.
Humans ; Male ; Cholesterol, LDL/blood* ; Female ; Myocardial Ischemia/drug therapy* ; Middle Aged ; Prospective Studies ; Aged ; Singapore/epidemiology* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Ezetimibe/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Shenting" (GV24) and "Baihui" (GV20) on mitochondrial autophagy in hippocampal neurons and silent information regulator sirtuin 1 (Sirt1)/forkhead box O3 (FOXO3)/PTEN-inducible kinase 1 (PINK1)/Parkin pathway in rats with learning-memory impairment after cerebral ischemia reperfusion injury. METHODS: A total of 35 male SD rats were randomly divided into a sham operation group (9 rats) and a modeling group (26 rats). In the modeling group, middle cerebral artery occlusion method was used to establish the middle cerebral artery ischemia-reperfusion (MCAO/R) model, and 18 rats of successful modeling were randomly divided into a model group and an EA group, 9 rats in each one. EA was applied at "Shenting" (GV24) and "Baihui" (GV20) in the EA group, 30 min a time, once a day for 14 days. After modeling and on 7th and 14th days of intervention, neurologic deficit score was observed; the learning-memory ability was detected by Morris water maze test; the morphology of neurons in CA1 area of hippocampus was detected by Nissl staining; the mitochondrial morphology was observed by transmission electron microscopy; the protein expression of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B), P62, Sitrt1, FOXO3, PINK1 and Parkin was detected by Western blot. RESULTS: After modeling, the neurologic deficit scores in the model group and the EA group were higher than that in the sham operation group (P<0.001); on 7th and 14th days of intervention, the neurologic deficit scores in the model group were higher than those in the sham operation group (P<0.001), the neurologic deficit scores in the EA group were lower than those in the model group (P<0.05, P<0.01). After modeling, the escape latency in the model group and the EA group was prolonged compared with that in the sham operation group (P<0.001); on 9th-13th days of intervention, the escape latency in the model group was prolonged compared with that in the sham operation group (P<0.001), the escape latency in the EA group was shortened compared with that in the model group (P<0.05, P<0.01, P<0.001). The number of crossing plateau in the model group was less than that in the sham operation group (P<0.001); the number of crossing plateau in the EA group was more than that in the model group (P<0.05). In the model group, in CA1 area of hippocampus, the number of neurons was less, with sparse arrangement, nuclear fixation, deep cytoplasmic staining, and reduction of Nissl substance; the morphology of mitochondrion was swollen, membrane structure was fragmented, and autophagic lysosomes were formed. Compared with the model group, in the EA group, in CA1 area of hippocampus, the number of neurons was increased, the number of cells of abnormal morphology was decreased, and the number of Nissl substance was increased; the morphology of mitochondrion was more intact and the number of autophagic lysosomes was increased. Compared with the sham operation group, in the model group, the protein expression of Beclin-1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰ ratio in hippocampus were increased (P<0.01, P<0.001), while the protein expression of P62 was decreased (P<0.05). Compared with the model group, in the EA group, the protein expression of Beclin-1, Sirt1, FOXO3, PINK1, Parkin and the LC3BⅡ/Ⅰratio in hippocampus were increased (P<0.001, P<0.01), while the protein expression of P62 was decreased (P<0.001). CONCLUSION EA at "Shenting" (GV24) and "Baihui" (GV20) can relieve the symptoms of neurological deficits and improve the learning-memory ability in MCAO/R rats, its mechanism may relate to the modulation of Sirt1/FOXO3/PINK1/Parkin pathway and the enhancement of mitochondrial autophagy.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Rats ; Forkhead Box Protein O3/genetics* ; Reperfusion Injury/metabolism* ; Ubiquitin-Protein Ligases/genetics* ; Brain Ischemia/complications* ; Mitochondria/genetics* ; Autophagy ; Protein Kinases/genetics* ; Sirtuin 1/genetics* ; Humans ; Memory Disorders/psychology* ; Signal Transduction

OBJECTIVE: To observe the effects of Xingnao Kaiqiao acupuncture technique (for regaining consciousness and opening orifice) on methylation of N6-methyladenosine (m6A), and key methyltransferases and demethylases, so as to clarify the mechanism of acupuncture on cerebral ischemia-reperfusion injury (CIRI). METHODS: Of 68 male Sprague-Dawley rats of SPF grade, 15 rats were randomly selected as a sham-operation group, and the remaining rats were subjected to the model of middle cerebral artery occlusion using the suture ligation. CIRI was induced by ischemia for 2 h followed by reperfusion. Rats that failed to modeling or died were excluded. The rest 45 rats were randomly divided into three groups, i.e. model group, acupuncture group, and non-point acupuncture group, with 15 rats in each group. The rats in the acupuncture group were treated with acupuncture at bilateral "Neiguan" (PC6) and "Shuigou" (GV26). In the non-point acupuncture group, acupuncture was delivered at three non-points, located 3 mm below the bilateral midaxillary line and 3 mm lateral to the tip of the coccyx. One intervention was operated in these two acupuncture groups and the needles were retained for 30 min. Before modeling start and 2 h after ischemia, a laser speckle flowmeter was used to monitor the cerebral blood perfusion. In 2 h of ischemia and 24 h of reperfusion, the neurological behavioral score was evaluated. The volume of rat cerebral infarction was determined by triphenyltetrazolium chloride (TTC) staining, and the level of m6A methylation in ischemic cortical area was detected by Dot blot, and the protein and mRNA expression of the demethylase i.e. fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and key methyltransferases, i.e. methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and Wilms' tumor 1-associated protein (WTAP) in ischemic cortical area were detected by Western blot and real-time PCR. RESULTS: Cerebral blood perfusion decreased by>70% after 2 h ischemia. Compared with the sham-operation group, the neurobehavioral score and the percentage of cerebral infarction volume increased in the model group (P<0.01); the level of m6A methylation in the ischemic cortical area increased (P<0.01), the protein and mRNA expression of FTO decreased (P<0.01), and that of ALKBH5, METTL3, and METTL14 increased (P<0.01, P<0.05) in the model group. When compared with the model group and the non-point acupuncture group, the acupuncture group showed a decrease in the neurobehavioral score and the percentage of cerebral infarction volume (P<0.01), the level of m6A methylation in the ischemic cortical area was reduced (P<0.01, P<0.05), and the protein and mRNA expression of FTO was elevated (P<0.01). CONCLUSION Xingnao Kaiqiao acupuncture technique presents its protective effect on the brain in the rats with CIRI, which is related to up-regulating the expression of FTO and modulating m6A methylation.
Animals ; Rats, Sprague-Dawley ; Male ; Acupuncture Therapy ; Reperfusion Injury/genetics* ; Rats ; Brain Ischemia/genetics* ; Humans ; Adenosine/metabolism* ; Methylation ; Acupuncture Points ; Cerebral Cortex/metabolism*