The Effect of Omega-3 Supplementation on Heart Failure Outcome: A Meta-Analysis of Randomized Clinical Trial.

The effect of omega-3 supplementation on cardiovascular (CV) disease has been widely studied in several large clinical trials. However, the evidence of the effect of omega-3 supplementation in patients with heart failure (HF) remains controversial. This meta-analysis investigated the effects of omega-3 supplementation on patients with HF. We conducted a literature search on MEDLINE, Embase, and Cochrane databases for clinical trials and preprints of relevant articles. Following a literature search and critical appraisal, 5 studies were included in the meta-analysis. The pooling of the result of the studies shows that there were no significant association between omega-3 supplementation and CV mortality (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.84-1.05, p=0.16) nor hospitalization due to HF (OR, 0.94; 95% CI, 0.88-1.02; p=0.13). Our systematic review and meta-analysis showed that omega-3 supplementation has no beneficial effect in patients with HF.

The potential of triglyceride-glucose index in improving the prediction of post-percutaneous coronary intervention clinical outcomes: a systematic review and meta-analysis.

INTRODUCTION: Despite percutaneous coronary intervention is the current preferred reperfusion modality, the incidence of major adverse cardiovascular events (MACE) is still high. Currently, GRACE score is used for predicting PCI outcomes. The TyG (triglyceride-glucose) index, a potential predictor based on insulin resistance of cardiovascular disease, has not been considered in the GRACE score. OBJECTIVE: To assess the potential of the TyG index in predicting cardiovascular adverse clinical outcomes in patients undergoing PCI. METHOD: Following PRISMA guidelines, the authors reviewed literature from five databases. We included studies investigating post-PCI outcomes based on the TyG index level. Effect size was estimated using RevMan to calculate pooled odds ratio and mean difference, and R software to perform diagnostic test accuracy. RESULTS: Overall, 31,671 post-PCI patients with acute coronary syndrome were included in this study. A significant difference in TyG index was found between patients who experienced MACE and those who did not [MD: 0.3 (0.2-0.4), p < .05]. Higher TyG index was strongly correlated with higher MACE [OR: 2.01 (1.45-2.77), p < .05], especially revascularization [OR: 2.40 (1.72-3.36), p < .05], followed by myocardial infarction [OR: 1.80 (2.41-2.86), p < .05], death [OR: 1.36 (0.86-2.15), p = .19], and stroke [OR: 1.09 (0.79-1.50), p = .59]. Tyg Index showed 55% sensitivity, 60% specificity, and 0.612 accuracy. The addition of the TyG index to the GRACE scoring improved the predictive model's AUC (0.746 vs. 0.809). CONCLUSION: This systematic review and meta-analysis comprises evidence-based results for the correlation of TyG index and post-PCI outcomes, demonstrating modest sensitivity, specificity, accuracy, and enhanced predictive value of GRACE score.

Current Evidence and Future Directions of Omega-3 Supplementation and Cardiovascular Disease Risk.

Omega-3 supplementation has a controversial role in the secondary prevention of cardiovascular diseases. Despite large clinical trials published over the years, the evidence of omega-3 in preventing cardiovascular diseases, especially coronary heart disease, is still inconclusive. However, recent clinical trials using higher dose of omega-3 or highly purified esters of omega-3 shows promising result, with reduction in cardiovascular death and incidence of cardiovascular disease. This review aims to summarize the possible mechanism of omega-3 in preventing cardiovascular disease and future directions of research regarding the benefit of omega-3 in cardiovascular disease.

The effect of resistance training on PCSK9 levels in patients undergoing cardiac rehabilitation after coronary artery bypass grafting: a randomized study.

BACKGROUND: Resistance training is commonly recommended as part of secondary prevention for post-coronary artery bypass graft (CABG) patients in conjunction with aerobic exercise. Despite its potential benefits, there is currently a lack of studies investigating the impact of resistance training on proprotein convertase subtilisin kexin 9 (PCSK9). AIM: To evaluate the effect of intensive resistance training on proprotein convertase subtilisin kexin 9 (PCSK9) levels among post-CABG patients undergoing cardiac rehabilitation (CR). METHODS: In this prospective, open-label, randomized trial, 87 post-coronary artery bypass graft (CABG) patients were randomly assigned into two groups: moderate to high intensity resistance training and aerobic training (n = 44) or aerobic training alone (n = 43) for a total of 12 sessions. Changes in PCSK9 levels was determined as a primary endpoint, while secondary endpoints included changes in the six-minute walk test (6-MWT) results, aerobic capacity, WHO-5 well-being index, fasting blood glucose, and lipid profile. Both groups underwent intention-to-treat analysis. RESULTS: Following completion of cardiac rehabilitation program, the intervention group demonstrated a significant decrease in mean PCSK9 levels when compared to the control group (ß = -55 ng/ml, 95% CI -6.7 to -103.3, p = 0.026), as well as significant improvements in the 6-MWT result (ß = 28.2 m, 95% CI 2.4-53.9, p = 0.033), aerobic capacity (ß = 0.9 Mets, 95% CI 0.1-1.7, p = 0.021), and WHO-5 well-being index (ß = 8.1, 95% CI 2.0-14.4, p = 0.011) in patients who received resistance and aerobic training. No statistically significant changes were observed in fasting blood glucose, cholesterol, LDL-C, HDL-C, and triglyceride levels. CONCLUSION: Resistance training in CR significantly reduced PCSK-9 levels and increases patient's functional capacity and quality of life. (NCT02674659 04/02/2016).

Gender Differences of Gly972Arg Polymorphism of the IRS-1 Gene Related to Cardiovascular Disease Risk Factors Among Indonesians.

BACKGROUND: Cardiovascular disease is driven by traditional risk factors, sex, and genetic differences. The Asian population, specifically Indonesians, has been known at high risk of insulin resistance and endothelial dysfunction. A possible genetic risk factor related to cardiovascular diseases is Gly972Arg polymorphism of insulin receptor substrate 1 (IRS-1) gene, as this impairs endothelial function. To date, whether there is a gender difference in Gly972Arg polymorphism of the IRS-1 gene in Indonesians is unknown. This study aimed to to define whether there is a gender difference in Gly972Arg polymorphism of the IRS-1 gene in Indonesians. METHODS: We studied adults living in two areas (rural and urban) in Indonesia. We collected demographic and clinical data from the study subjects. Gly972Arg polymorphism of the IRS-1 gene (rs1801278) was detected using TaqMan real-time polymerase chain reaction. RESULTS: A total of 378 subjects were recruited. The wild-type allele (CC) was found in 86 (22.8%) subjects, heterozygous mutant allele (CT) in 245 (64.8%), and homozygous mutant allele in 47 (12.4%). The proportion of subjects with T alleles was significantly higher among women than men (54.6% vs. 45.4%, odds ratio: 1.89; p = 0.01). Subjects with T allele more often have hypertension (odds ratio: 1.69, p = 0.058). CONCLUSION: There were a higher proportion of women than men carrying the T allele of Gly972Arg polymorphism among Indonesians. Individuals with the T allele appeared to show a greater prevalence of hypertension. These results may explain a possible mechanism of the high prevalence of metabolic syndrome in Indonesia, especially in women.

Smartphone-Based Cardiac Rehabilitation Program Improves Functional Capacity in Coronary Heart Disease Patients: A Systematic Review and Meta-Analysis.

Cardiac rehabilitation (CR) reduces mortality and morbidity in coronary heart disease (CHD); however, patients show a lack of adherence to CR. Alternatively, telehealth interventions have shown promising results for improving target outcomes in CR. This study aimed to review the effect of smartphone-based CR on the functional capacity of CHD patients. A literature search was performed using PubMed, MEDLINE, Embase, and Cochrane Library on 21 March, 2022 to find randomised controlled trials on smartphone usage in CR to improve functional capacity. Outcomes included maximal oxygen consumption (VO2 max), a 6-min walk test (6-MWT), quality of life, smoking cessation, and modifiable risk factors. Eleven trials recruiting CHD patients were reviewed. Wearable devices connected to smartphone- or chat-based applications were commonly used for CR delivery. Most trials managed to provide exercise prescriptions, education on medication adherence and controlling risk factors, and psychosocial counselling through the intervention. Functional capacity improved significantly following smartphone-based CR in CHD patients compared to control groups, as measured by VO2 max and 6-MWT; patients were more likely to quit smoking. Compared to traditional care, smartphones that delivered CR to CHD patients demonstrate superior outcomes regarding increasing functional capacity. There is no significant improvement on lipid profile, blood pressure, HbA1C, body mass index, and quality of life. It can be used either alone or as an adjunct. Ultimately, the patients' preferences and circumstances should be considered.

Anti-Inflammatory, Antioxidant, Metabolic and Gut Microbiota Modulation Activities of Probiotic in Cardiac Remodeling Condition: Evidence from Systematic Study and Meta-Analysis of Randomized Controlled Trials.

Heart failure (HF) is a global pandemic with increasing prevalence and mortality rates annually. Its main cause is myocardial infarction (MI), followed by rapid cardiac remodeling. Several clinical studies have shown that probiotics can improve the quality of life and reduce cardiovascular risk factors. This systematic review and meta-analysis aimed to investigate the effectiveness of probiotics in preventing HF caused by a MI according to a prospectively registered protocol (PROSPERO: CRD42023388870). Four independent evaluators independently extracted the data using predefined extraction forms and evaluated the eligibility and accuracy of the studies. A total of six studies consisting of 366 participants were included in the systematic review. Probiotics are not significant in intervening left ventricular ejection fraction (LVEF) and high-sensitivity C-reactive protein (hs-CRP) when compared between the intervention group and the control group due to inadequate studies supporting its efficacy. Among sarcopenia indexes, hand grip strength (HGS) showed robust correlations with the Wnt biomarkers (p < 0.05), improved short physical performance battery (SPPB) scores were also strongly correlated with Dickkopf-related protein (Dkk)-3, followed by Dkk-1, and sterol regulatory element-binding protein 1 (SREBP-1) (p < 0.05). The probiotic group showed improvement in total cholesterol (p = 0.01) and uric acid (p = 0.014) compared to the baseline. Finally, probiotic supplements may be an anti-inflammatory, antioxidant, metabolic, and intestinal microbiota modulator in cardiac remodeling conditions. Probiotics have great potential to attenuate cardiac remodeling in HF or post-MI patients while also enhancing the Wnt signaling pathway which can improve sarcopenia under such conditions.

A Novel Peptide Elabela is Associated with Hypertension-Related Subclinical Atherosclerosis.

INTRODUCTION: Elabela is a newly identified peptide which, alongside apelin, acts as an endogenous ligand that activates the angiotensin receptor-like 1 receptor. Previous studies have shown the association of elabela with hypertension, but information about the role of elabela in hypertension-related subclinical atherosclerosis is scarce. AIM: We aimed to determine the elabela levels in hypertensive patients and explore its association with subclinical atherosclerosis. METHODS: A total of 104 subjects with hypertension were included in the study. Elabela levels were measured using an enzyme-linked immunosorbent assay, by first extracting the peptide following the manufacturer's instructions. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (IMT) using ultrasound. RESULTS: Compared to stage 1, elabela levels decreased in stage 2 hypertension (0.23 [0.13, 0.45] ng/ml vs. 0.14 [0.09, 0.23] ng/ml; P = 0.000), and in the group with increased carotid IMT compared to normal IMT (0.24 [0.13, 0.38] ng/ml vs. 0.15 [0.10, 0.23] ng/ml; P = 0.005). Additionally, a linear correlation analysis showed that elabela had a significant negative correlation with systolic blood pressure (r = - 0.340, P = 0.000) and carotid IMT (r = - 0.213; P = 0.030). In multivariate analysis, lower elabela levels were associated with a higher cardiovascular risk group in this study (OR 5.0, 95% CI 1.8-13.5, P < 0.001). CONCLUSIONS: This study demonstrated for the first time that circulating elabela declined in a higher stage of hypertension and hypertensive patients with increased carotid IMT, implicating that elabela may be involved in the pathogenesis of hypertension-associated subclinical atherosclerosis.

External Counterpulsation Improves Angiogenesis by Preserving Vascular Endothelial Growth Factor-A and Vascular Endothelial Growth Factor Receptor-2 but Not Regulating MicroRNA-92a Expression in Patients With Refractory Angina.

Objective: External counterpulsation (ECP) provides long-term benefits of improved anginal frequency and exercise tolerance in patients with refractory angina (RA). This is postulated as a result of improved angiogenesis and endothelial function through an increase in shear stress. Angiogenesis is mainly represented by vascular endothelial growth factor-A (VEGF-A) and its receptor, vascular endothelial growth factor receptor-2 (VEGFR-2). The microRNA-92a (miR-92a) is a flow-sensitive miRNA that regulates atherosclerosis and angiogenesis in response to shear stress. Thus, ECP beneficial effect might be achieved through interaction between VEGF-A, VEGFR-2, and miR-92a. This study aims to evaluate the ECP effect on VEGF-A, VEGFR-2, and miR-92a in patients with RA in a sham-controlled manner. Methods: This was a randomized sham-controlled trial, enrolling 50 patients with RA who have coronary artery disease (CAD). Participants were randomized (1:1 ratio) to 35 sessions of either ECP (n = 25) or sham (n = 25), each session lasting for 1 h. Plasma levels of VEGF-A and VEGFR-2 were assayed by the ELISA technique. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to measure miR-92a circulating levels in plasma. Result: External counterpulsation significantly preserved VEGF-A and VEGFR-2 level compared to sham [ΔVEGF-A: 1 (-139 to 160) vs.-136 (-237 to 67) pg/ml, p = 0.026; ΔVEGFR-2: -171(-844 to +1,166) vs. -517(-1,549 to +1,407) pg/ml, p = 0.021, respectively]. Circulating miR-92a increased significantly in ECP [5.1 (4.2-6.4) to 5.9 (4.8-6.4), p < 0.001] and sham [5.2 (4.1-9.4) to 5.6 (4.8-6.3), p = 0.008] post-intervention. The fold changes tended to be higher in ECP group, although was not statistically different from sham [fold changes ECP = 4.6 (0.3-36.5) vs. sham 2.8 (0-15), p = 0.33)]. Conclusion: External counterpulsation improved angiogenesis by preserving VEGF-A and VEGFR-2 levels. Both ECP and sham increased miR-92a significantly, yet the changes were not different between the two groups. (Study registered on www.clinicaltrials.gov, no: NCT03991871, August 8, 2019, and received a grant from the National Health Research and Development of Ministry of Health of Indonesia, No: HK.02.02/I/27/2020).

Asian Pacific Society of Cardiology Consensus Recommendations for Pre-participation Screening in Young Competitive Athletes.

Sports-related sudden cardiac death is a rare but devastating consequence of sports participation. Certain pathologies underlying sports-related sudden cardiac death could have been picked up pre-participation and the affected athletes advised on appropriate preventive measures and/or suitability for training or competition. However, mass screening efforts - especially in healthy young populations - are fraught with challenges, most notably the need to balance scarce medical resources and sustainability of such screening programmes, in healthcare systems that are already stretched. Given the rising trend of young sports participants across the Asia-Pacific region, the working group of the Asian Pacific Society of Cardiology (APSC) developed a sports classification system that incorporates dynamic and static components of various sports, with deliberate integration of sports events unique to the Asia-Pacific region. The APSC expert panel reviewed and appraised using the Grading of Recommendations Assessment, Development, and Evaluation system. Consensus recommendations were developed, which were then put to an online vote. Consensus was reached when 80% of votes for a recommendation were agree or neutral. The resulting statements described here provide guidance on the need for cardiovascular pre-participation screening for young competitive athletes based on the intensity of sports they engage in.

Determinants and Prediction Equations of Six-Minute Walk Test Distance Immediately After Cardiac Surgery.

Background: To date, there is no reference for a 6-min walk test distance (6-MWD) immediately after cardiac surgery. Therefore, this study aimed to identify the determinants and to generate equations for prediction reference for 6-MWD in patients immediately after cardiac surgery. Methods: This is a cross-sectional study of the 6-min walk test (6-MWT) prior to participation in the cardiac rehabilitation (CR) program of patients after coronary artery bypass surgery (CABG) or valve surgery. The 6-MWT were carried out in a gymnasium prior to the CR program immediately after the cardiac surgery. Available demographic and clinical data of patients were analyzed to identify the clinical determinants of 6-MWD. Results: This study obtained and analyzed the data of 1,509 patients after CABG and 632 patients after valve surgery. The 6-MWD of all patients was 321.5 ± 73.2 m (60-577). The distance was longer in the valve surgery group than that of patients in the CABG group (327.75 ± 70.5 vs. 313.59 ± 75.8 m, p < 0.001). The determinants which significantly influence the 6-MWD in the CABG group were age, gender, diabetes, atrial fibrillation, and body height, whereas in the valve surgery group these were age, gender, and atrial fibrillation. The multivariable regression models generated two formulas using the identified clinical determinants for patients after CABG: 6-MWD (meter) = 212.57 + 30.47 (if male gender) - 1.62 (age in year) + 1.09 (body height in cm) - 12.68 (if with diabetes) - 28.36 (if with atrial fibrillation), and for patients after valve surgery with the formula: 6-MWD (meter) = 371.05 + 37.98 (if male gender) - 1.36 (age in years) - 10.61 (if atrial with fibrillation). Conclusion: This study identified several determinants for the 6-MWD and successively generated two reference equations for predicting 6-MWD in patients after CABG and valve surgery.

Case Report: Heparin-induced thrombocytopenia during COVID-19 outbreak: the importance of scoring system in differentiating with sepsis-induced coagulopathy.

Background: COVID-19 disease is accompanied by derangement of coagulation with a risk of fatal thromboembolic formation. COVID-19 patients are among those indicative for heparin treatment. Increased heparin administration among COVID-19 patients increased heparin induced-thrombocytopenia's risk with/without thrombocytopenia. Case presentation: We present a 71-year-old male patient who came to the emergency room (ER) with a COVID-19 clinical manifestation followed by positive PCR nasopharyngeal swab result. He was assessed to have acute respiratory distress syndrome (ARDS), as shown by rapid progression of hypoxemic respiratory failure and bilateral pulmonary infiltrate. He was then treated with moxifloxacin, remdesivir, dexamethasone, unfractionated heparin (UFH) pump, and multivitamins. During admission, his respiratory symptoms got worse, so he transferred to the ICU for NIV support. On the ninth day of admission, he had gross hematuria followed by a rapid fall of platelet count. We used two different scoring systems (4Ts and HEP scoring system) to confirm the diagnosis of heparin-induced thrombocytopenia (HIT). Following the discontinuation of UFH injection, the thrombocyte continued to rise, and hematuria disappeared. Conclusion: Heparin-induced thrombocytopenia is associated with an increased risk of severe disease and mortality among COVID-19 patients. The differential diagnosis of HIT could be difficult as thrombocytopenia can also be caused by the progression of infection. We use two scoring systems (4Ts and HEP scoring) in order to help us managing the patient. These could improve the outcomes, thus avoiding morbidity and mortality.

Randomised controlled trial into the role of ramipril in fibrosis reduction in rheumatic heart disease: the RamiRHeD trial protocol.

INTRODUCTION: Rheumatic heart disease (RHD) is a major burden in developing countries and accounts for 80% of all people living with the disease, where it causes most cardiovascular morbidity and mortality in children and young adults. Chronic inflammation and fibrosis of heart valve tissue due to chronic inflammation in RHD will cause calcification and thickening of the impacted heart valves, especially the mitral valve. This fibrogenesis is enhanced by the production of angiotensin II by increased transforming growth factor ß expression and later by the binding of interleukin-33, which is known to have antihypertrophic and antifibrotic effects, to soluble sST2. sST2 binding to this non-natural ligand worsens fibrosis. Therefore, we hypothesise that ACE inhibitors (ACEIs) would improve rheumatic mitral valve stenosis. METHODS AND ANALYSIS: This is a single-centre, double-blind, placebo-controlled, randomised clinical trial with a pre-post test design. Patients with rheumatic mitral stenosis and valve dysfunction will be planned for cardiac valve replacement operation and will be given ramipril 5 mg or placebo for a minimum of 12 weeks before the surgery. The expression of ST2 in the mitral valve is considered to be representative of cardiac fibrosis. Mitral valve tissue will be stained by immunohistochemistry to ST2. Plasma ST2 will be measured by ELISA. This study is conducted in the Department of Cardiology and Vascular Medicine, Universitas Indonesia, National Cardiac Center Harapan Kita Hospital, Jakarta, Indonesia, starting on 27 June 2019. ETHICS AND DISSEMINATION: The performance and dissemination of this study were approved by the ethics committee of National Cardiovascular Center Harapan Kita with ethical code LB.02.01/VII/286/KEP.009/2018. TRIAL REGISTRATION NUMBER: NCT03991910.

The Effects of Aerobic Exercise on N-terminal Pro-B-type Natriuretic Peptide and Cardiopulmonary Function in Patients With Heart Failure: A Meta-Analysis of Randomised Clinical Trials.

BACKGROUND: Aerobic exercise (AEx) improves outcomes in heart failure (HF). N-terminal pro B-type natriuretic peptide (NT-pro-BNP) is a prognosticator in HF. There are few data on the association of AEx, NT-pro-BNP, and cardiopulmonary function; hence, robust evidence is needed. The aim of this study was to measure the effects of AEx on NT-pro-BNP levels and cardiopulmonary function in HF. METHOD: Databases (Pubmed, EMBASE, Medline, Cochrane Central Registry, and Scopus) were systematically searched for randomised controlled trials (RCTs) that assessed the association of AEx with NT-pro-BNP and cardiopulmonary function (VE/VCO2 slope, peak VO2, maximal workload, and left ventricular ejection fraction [LVEF]) in HF. RevMan 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, 2014) was used to produce forest plots, and the random-effect model was applied with the effects measure of weighted mean differences (WMD) and 95% confidence interval (CI). RESULTS: Thirteen (13) RCTs recruited 1,503 patients and 1,494 controls. Aerobic exercise was significant in lowering NT-pro-BNP (pg/mL) compared with control group (WMD=-741.69, 95% CI -993.10 to -490.27 [p<0.00001; I2=63%]). VE/VCO2 slope was also significantly reduced (WMD=-3.57, 95% CI -6.48 to -0.67 [p=0.02; I2=97%]). Peak VO2 (mL/kg/min) significantly improved (WMD=3.68, 95% CI 2.39-4.96 [p<0.00001; I2=96%]). Maximal workload (watt) significantly increased following AEx (WMD=22.80, 95% CI 18.44-27.17 [p<0.00001; I2=78%]). Furthermore, there was a significant enhancement of LVEF (%) in the AEx group (WMD=2.42, 95% CI 0.64-4.19 [p=0.008; I2=71%]). CONCLUSIONS: Aerobic exercise improves the NT-pro-BNP, ventilatory efficiency, aerobic capacity, maximal workload, and the left ventricular function in patients with HF.