The association of right ventricular-pulmonary arterial coupling and pulmonary vascular resistance in adult patients with uncorrected atrial septal defect.

BACKGROUND: Atrial septal defects (ASD) are the most common type of adult congenital heart disease (ACHD) associated with a high risk developing of pulmonary arterial hypertension (PAH). ASD closure is not recommended in patients with PAH and Pulmonary Vascular Resistance (PVR) ≥ 5 Wood Unit (WU). Noninvasive methods have been proposed to measure PVR; however, their accuracy remains low. Right Ventricle (RV) - Pulmonary Artery (PA) coupling is defined as the ability of the RV to adapt to high-resistance conditions. Tricuspid Annular Plane Systolic Excursion (TAPSE)/estimated pulmonary artery systolic pressure (ePASP) calculation using echocardiography is a noninvasive technique that has been proposed as a surrogate equation to evaluate RV-PA coupling. Currently, no research has demonstrated a relationship between RV-PA coupling and PVR in patients with ASD. METHODS: The study participants were consecutive eligible patients with ASD who underwent right heart catheterization (RHC) and echocardiography at Hasan Sadikin General Hospital, Bandung. Both the procedures were performed on the same day. RV-PA Coupling, defined as TAPSE/ePASP > 0.31, was assessed using echocardiography. The PVR was calculated during RHC using the indirect Fick method. RESULTS: There were 58 patients with ASD underwent RHC and echocardiography. Among them, 18 had RV/PA Coupling and 40 had RV/PA Uncoupling. The PVR values were significantly different between the two groups (p = 0.000). Correlation test between TAPSE/ePASP with PVR showed moderate negative correlation (r= -0.502, p = 0.001). TAPSE/ePASP ≤ 0.34 is the cutoff point to predict PVR > 5 WU with sensitivity of 91.7% and specificity 63.6%. CONCLUSION: This study showed a moderate negative correlation between TAPSE/ePASP and PVR. TAPSE/ePASP ≤ 0.34 could predict PVR > 5 WU with good sensitivity.

Factors influencing coronary artery target lesion revascularization after drug-coated balloon angioplasty.

Background: Concerns regarding restenosis after treatment with drug-coated balloons (DCB) remain. We aimed to identify the incidence of target lesion revascularization (TLR) and explore clinical, procedural, and other factors influencing it. Methods: Single-center retrospective analysis of a prospective cohort PCI registry study included 80 patients (100 lesions) who underwent successful DCB angioplasty between January 2020 and October 2023 and follow-up angiography within 2 years of either planned or unplanned reason. Incidence and factors associated with TLR were analyzed. Results: Angiographic evaluation was conducted within a median of 151 days (interquartile range: 109 days). During index procedure, 54% were complex lesions. Intravascular imaging (IVI) was performed in 80% of lesions. TLR occurred in 11% of the lesions and was less frequent in the IVI group compared to the angiography-alone group [6.3 vs. 54.5%; odds ratio: 0.156, 95% confidence interval (CI): 0.042-0.580; p = 0.002]. No association was found between baseline and lesion characteristics, lesion complexity, plaque morphology, pre-dilatation procedure balloon type, maximal inflation pressure, or length of DCB between the groups (p > 0.05). Multivariate analysis revealed that IVI utilization was independently associated with a lower TLR rate (adjusted odds ratio: 0.116, 95% CI: 0.020-0.669; p = 0.016). Conclusion: In DCB angioplasty, only IVI use exhibited a significant difference in the TLR rate among baseline lesion characteristics and lesion preparation and was independently associated with a lower TLR rate.

The molecular interaction of six single-stranded DNA aptamers to cardiac troponin I revealed by docking and molecular dynamics simulation.

Cardiac troponin I (cTnI) is a cardiac biomarker for diagnosing ischemic heart disease and acute myocardial infarction. Current biochemical assays use antibodies (Abs) due to their high specificity and sensitivity. However, there are some limitations, such as the high-cost production of Abs due to complex instruments, reagents, and steps; the variability of Abs quality from batch to batch; the low stability at high temperatures; and the difficulty of chemical modification. Aptamer overcomes the limitations of antibodies, such as relatively lower cost, high reproducibility, high stability, and ease of being chemically modified. Aptamers are three-dimensional architectures of single-stranded RNA or DNA that bind to targets such as proteins. Six aptamers (Tro1-Tro6) with higher binding affinity than an antibody have been identified, but the molecular interaction has not been studied. In this study, six DNA aptamers were modeled and docked to cTnI protein. Molecular docking revealed that the interaction between all aptamer and cTnI happened in the similar cTnI region. The interaction between aptamer and cTnI involved hydrophobic interaction, hydrogen bonds, π-cation interactions, π-stack interactions, and salt-bridge formation. The calculated binding energy of all complexes was negative, which means that the complex formation was thermodynamically favorable. The electrostatic energy term was the main driving force of the interaction between all aptamer and cTnI. This study could be used to predict the behavior of further modified aptamer to improve aptamer performance.

Strong Association of Metabolic Parameters with ADMA and VCAM-1 in Normo-Weight Subjects with Metabolic Syndrome.

Background: Metabolic syndrome (MetS) is a risk factor for cardiovascular disease and is linked to obesity. Subjects with MetS who have normo-weight potentially show higher mortality and morbidity. Purpose: This study aims to reveal the critical essential metabolic parameters associated with endothelial dysfunction in MetS subjects with normo-weight compared to obese. Patients and Methods: The study was designed using a case-control approach. Ninety-nine MetS subjects (34 Normo-weight and 65 obese) from the urban population were enrolled in this study. The components of MetS are based on NCEP/ATP III criteria. Asymmetric dimethylarginine (ADMA) and vascular cell adhesion molecule 1 (VCAM-1) as markers for endothelial dysfunction were measured in both groups. Results: Fasting blood glucose (FBG) levels were higher in the normo-weight group (143.38 ± 79.8 mg/dL) compared to the obese group (120.89 ± 46.5 mg/dL). High-density lipoprotein cholesterol (HDL-c) levels in the normo-weight group were lower (42.82 ± 10.1 mg/dL) compared to obesity (45.74 ± 9.3 mg/dL), while triacylglycerol (TAG) levels were higher in the obese (197.25 ± 110.5 mg/dL) compared to the normo-weight group (167.03 ± 98.4 mg/dL), although the differences were statistically not significant (all p > 0.05). The difference between ADMA and VCAM-1 levels was statistically not significant in both groups. Correlation between MetS components with endothelial dysfunction parameters shows that metabolic parameters correlate strongly. Interestingly, a stronger correlation between FBG and ADMA was observed in normo-weight (r = 0.519) compared to obese groups (r = 0.445). In addition, TAG consistently shows a significant correlation with ADMA and VCAM-1 in normo-weight groups. Conclusion: Metabolic parameters, especially FBG and TAG, correlate strongly with endothelial dysfunction parameters in normo-weight subjects with metabolic syndrome.

Relationship between serum soluble suppression of tumorigenicity (ST) 2 and global longitudinal strain in early onset preeclampsia.

BACKGROUND: Preeclampsia is one of the leading causes of death in childbearing women worldwide. Hemodynamic changes in preeclampsia can trigger cardiac remodeling as indicated by increase of soluble-ST2 (sST2). Global longitudinal strain were able to detect systolic dysfunction better than the ejection fraction. This study aims to evaluate the correlation between serum levels of sST2 towards GLS in patients with early-onset preeclampsia. METHODS: This is a cross-sectional observational study with correlation analysis. Subjects were patients with severe preeclampsia with gestational age before 34 weeks at Dr. Hasan Sadikin Central General Hospital Bandung and Bandung Kiwari Regional General Hospital from June to August 2022. Examination of sST2 was carried out through blood samples using the ELISA method. sST2 was measured using Presage ST2 Assay reagent. GLS examination was carried out using speckle tracking technique with EchoPAC. Correlation analysis was conducted using the Pearson test if normally distributed, otherwise Spearman's correlation was conducted. Correlation analysis was followed by linear regression. RESULTS: A total of 30 patients met the inclusion criteria. The mean age was 30.83 ± 7.09, with 17 (56.7%) multiparous patients. The median sST2 was 145.75 ng/mL, and the median GLS was - 17.4%. Spearman correlation analysis showed that there was a significant positive correlation with moderate strength between sST2 and GLS (r = 0.583; p < 0.002). Linear regression showed that every 1 ng/ml increase in sST2 would give an increase in GLS of 0.014%. CONCLUSION: There is a significant correlation between sST2 and GLS in patients with early onset severe preeclampsia.

The pivotal role of compelling high-risk electrocardiographic markers in prediction of ventricular arrhythmic risk in arrhythmogenic right ventricular cardiomyopathy: A systematic review and meta-analysis.

INTRODUCTION: Several investigations have shown that existing risk stratification processes remain insufficient for stratifying sudden cardiac death risk in arrhythmogenic right ventricular cardiomyopathy (ARVC). Multiple auxiliary parameters are investigated to offer a more precise prognostic model. Our aim was to assess the association between several ECG markers (epsilon waves, prolonged terminal activation duration (TAD) of QRS, fragmented QRS (fQRS), late potentials on signal-averaged electrocardiogram (SA-ECG), T-wave inversion (TWI) in right precordial leads, and extension of TWI in inferior leads) with the risk of developing poor outcomes in ARVC. METHODS: A systematic literature search from several databases was conducted until September 9th, 2023. Studies were eligible if it investigated the relationship between the ECG markers with the risk of developing ventricular arrhythmic events. RESULTS: This meta-analysis encompassed 25 studies with a total of 3767 participants. Our study disclosed that epsilon waves, prolonged TAD of QRS, fQRS, late potentials on SA-ECG, TWI in right precordial leads, and extension of TWI in inferior leads were associated with the incremental risk of ventricular arrhythmias, implantable cardioverter-defibrillator shock, and sudden cardiac death, with the risk ratios ranging from 1.46 to 2.11. In addition, diagnostic test accuracy meta-analysis stipulated that the extension of TWI in inferior leads had the uppermost overall area under curve (AUC) value amidst other ECG markers apropos of our outcomes of interest. CONCLUSION: A multivariable risk assessment strategy based on the previously stated ECG markers potentially enhances the current risk stratification models in ARVC patients, especially extension of TWI in inferior leads.

A Meta-Analysis of Atrial Septal Defect Closure in Patients With Severe Pulmonary Hypertension: Is There a Room for Poking Holes Amid Debate?

Severe pulmonary arterial hypertension (PAH) associated with atrial septal defect (ASD) poses a challenge to a closure of ASD, particularly severe PAH that persists even after pharmacological therapeutic strategy. Our study was aimed to evaluate this matter. A systematic literature search from several databases was conducted up until August 1st, 2023. A meta-analysis was undertaken on studies that reported hemodynamic measurements in ASD patients with severe PAH before and after closure. The primary objectives were the extent of improvement in all hemodynamic parameters following closure, and the secondary outcomes were major adverse cardiac events (MACEs) during follow-up. Our study comprised 10 studies with a total of 207 participants. Patients were divided into treat-and-repair and straight-to-repair groups based on the therapeutic strategy. Meta-analysis of all studies demonstrated significant improvement in mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), pulmonary vascular resistance index (PVRI), 6-minutes walking distance (6MWD), and lower prevalence of World Health Organization functional classes (WHO fc), particularly in the treat-and-repair strategy subgroup. Additionally, merely 4 of the 156 individuals died from cardiac causes, and only 1 required rehospitalization, indicating a low likelihood of MACEs arising. Our new findings support the notion that effective shunt closure can improve various hemodynamic parameters in carefully chosen patients with noncorrectable ASD-PAH. Further large and prospective observational studies are still warranted to validate these findings.

Predicting poor left ventricular function recovery in Peripartum cardiomyopathy.

INTRODUCTION: Peripartum cardiomyopathy (PPCM) is a rare type of cardiomyopathy that manifests as acute heart failure associated with pregnancy. Delays in early identification result in poor recovery of left ventricular (LV) function; however, no risk prediction model exists. We sought to yield a scoring system known as the Padjadjaran Peripartum CardioMyopathy Recovery (PPCM recovery) score to predict the probability of poor LV function recovery in PPCM patients. METHODS: All baseline and clinical parameters were prospectively collected from a cohort of patients with PPCM admitted to Dr. Hasan Sadikin General Hospital in Bandung, Indonesia between January 2014 and December 2021. Logistic regression analyses were performed to investigate the relationship between each variable and the risk of poor LV function recovery in PPCM patients. RESULTS: This prospective cohort study included 113 patients with PPCM (84 recovered and 29 non-recovered patients). Significant mitral regurgitation (MR), left ventricular ejection fraction (LVEF) <30%, left ventricular end-diastolic diameter (LVEDD) ≥56 mm, and New York Heart Association functional class (NYHA FC) IV were all strong predictors of poor LV function recovery. These variables were integrated into the PPCM recovery score (AUC of 0.85). Patients with a score of ≥8 were nearly 18 times more likely to have poor LV function recovery (sensitivity 57%, specificity 93%). CONCLUSION: PPCM recovery score is a convenient scoring system based on clinical and echocardiography assessment that may assist in distinguishing which patients are more likely to develop poor LV function recovery; therefore, these patients should be immediately referred to a tertiary referral hospital.

A Revised PADMA Scoring System for Predicting in-Hospital Mortality in Acute Coronary Syndrome Patient.

Background: In order to predict in-hospital mortality in ACS (Acute Coronary Syndrome) patients based solely on clinical examination, this study compares the shock index (heart rate divided by systolic blood pressure) variable in PADMA (PADjadjaran Mortality in Acute Coronary Syndrome) with the modified shock index (heart rate divided by mean arterial pressure) score. The predictive efficacy of the PADMA score in predicting in-hospital mortality in ACS patients has been in doubt up until recently. Methods: All ACS patients above the age of 18 who were admitted to Dr. Hasan Sadikin Central General Hospital between January 2018 and January 2023 were included in this retrospective observational cohort study. This study did not involve any interventions, and verbal informed permission was obtained with the Hasan Sadikin Hospital Ethic Committee's approval. Multivariate logistic regression was used to gather and evaluate patient demographic, comorbidity, and clinical presentation data in order to provide two scoring systems (probability and cut-off models) that can be used to predict in-hospital all-cause death. The Fisher Z test was used to assess the area under the curve (AUC) between the PADMA SI (shock index) and PADMA MSI (modified shock index). Results: Killip classifications III and IV, tachycardia, a high shock index, and older age were found to be independent mortality predictors and were included to the PADMA MSI score by multivariate regression analysis of 1504 people. PADMA SI score >8 has a sensitivity of 67.92% and a specificity of 84.01% for predicting all-cause death. The range of the PADMA SI score is 0 to 19. The AUC between the PADMA MSI and PADMA SI scores did not differ significantly (p=0.022). Conclusion: Similar to the PADMA SI score, the PADMA MSI score >8 demonstrated an accurate discriminative power to forecast in-hospital mortality though it did not have significant statistic difference.

The assessment of molecular dynamics results of three-dimensional RNA aptamer structure prediction.

Aptamers are single-stranded DNA or RNA that bind to specific targets such as proteins, thus having similar characteristics to antibodies. It can be synthesized at a lower cost, with no batch-to-batch variations, and is easier to modify chemically than antibodies, thus potentially being used as therapeutic and biosensing agents. The current method for RNA aptamer identification in vitro uses the SELEX method, which is considered inefficient due to its complex process. Computational models of aptamers have been used to predict and study the molecular interaction of modified aptamers to improve affinity. In this study, we generated three-dimensional models of five RNA aptamers from their sequence using mFold, RNAComposer web server, and molecular dynamics simulation. The model structures were then evaluated and compared with the experimentally determined structures. This study showed that the combination of mFold, RNAComposer, and molecular dynamics simulation could generate 14-16, 28, or 29 nucleotides length of 3D RNA aptamer with similar geometry and topology to the experimentally determined structures. The non-canonical basepair structure of the aptamer loop was formed through the MD simulation, which also improved the three-dimensional RNA aptamers model. Clustering analysis was recommended to choose the more representative model.

The soluble suppression of tumorigenicity 2 as a biomarker of early cardiac remodeling in bradycardia patients receiving permanent pacemaker therapy.

Aim: This study aims to evaluate: the difference of soluble suppression of tumorigenicity 2 (sST2) level, a biomarker for cardiac remodeling and echocardiography parameters value prior to and 1 month after implantation; and the association between pacemaker parameters and pacemaker mode along with delta sST2 levels. Materials & methods: This prospective cohort study enrolled all symptomatic bradycardia patients aged >18 years with preserved ejection fraction who underwent permanent pacemaker (PPM) implantation. Results: A total of 49 patients were included in this study. The sST2 level (ng/ml) were significantly different between prior and 1 month following PPM implantation (23.4 ± 28.4 vs 39.9 ± 63.7; p = 0.001). Conclusion: The early cardiac remodeling has occurred within 1 month after PPM implantation as indicated by increasing delta sST2 level.

It is widely known that pacing induced cardiomyopathy, which results from the utilization of a permanent pacemaker (PPM) within a long-term duration, will increase the risk of mortality and morbidity. Hence, early detection of the cardiac remodeling process is warranted in order to prevent this course. In this study, the soluble suppression of tumorigenicity 2 level (ng/ml), known as an indicator of cardiac remodeling, was significantly higher in 1 month following PPM implantation compared with the baseline (23.4 ± 28.4 vs 39.9 ± 63.7; p = 0.001). Thus, it denotes that early cardiac remodeling might occur earlier than expected, within 1 month following PPM implantation.

Investigation of High-Risk Electrocardiographic Markers as Predictors of Major Arrhythmic Events in Brugada Syndrome: A Systematic Review and Meta-analysis.

Numerous studies have demonstrated that a type I Brugada electrocardiographic (ECG) pattern, history of syncope, prior sudden cardiac arrest, and previously documented ventricular tachyarrhythmias are still insufficient to stratify the risk of sudden cardiac death in Brugada syndrome (BrS). Several auxiliary risk stratification parameters are pursued to yield a better prognostic model. Our aim was to assess the association between several ECG markers (wide QRS, fragmented QRS, S-wave in lead I, aVR sign, early repolarization pattern in inferolateral leads, and repolarization dispersion pattern) with the risk of developing poor outcomes in BrS. A systematic literature search from several databases was conducted from database inception until August 17th, 2022. Studies were eligible if it investigated the relationship between the ECG markers with the likelihood of acquiring major arrhythmic events (MAE). This meta-analysis comprised 27 studies with a total of 6552 participants. Our study revealed that wide QRS, fragmented QRS, S-wave in lead I, aVR sign, early repolarization pattern in inferolateral leads, and repolarization dispersion ECG pattern were associated with the incremental risk of syncope, ventricular tachyarrhythmias, implantable cardioverter-defibrillator shock, and sudden cardiac death in the future, with the risk ratios ranging from 1.41 to 2.00. Moreover, diagnostic test accuracy meta-analysis indicated that the repolarization dispersion ECG pattern had the highest overall area under curve (AUC) value amid other ECG markers regarding our outcomes of interest. A multivariable risk assessment approach based on the prior mentioned ECG markers potentially improves the current risk stratification models in BrS patients.

Role of N-terminal pro-B type natriuretic peptide as a predictor of poor outcomes in patients with HFrEF receiving primary prevention implantable cardioverter-defibrillator therapy: a systematic review and dose-response meta-analysis.

INTRODUCTION: Several studies have demonstrated that combining left ventricular ejection fraction and New York Heart Association functional class is insufficient for predicting risk of appropriate implantable cardioverter-defibrillator (ICD) shock in primary prevention candidates. Hence, our aim was to assess the relationship between N-terminal pro-B type natriuretic peptide (NT-pro BNP) along with appropriate ICD shock and all-cause mortality in order to improve the stratification process of patients with heart failure with reduced ejection fraction (HFrEF) being considered for primary preventive ICD therapy. METHODS: A systematic literature search from several databases was conducted up until 9 June 2022. Studies were eligible if they investigated the relationship of NT-pro BNP with all-cause mortality and appropriate ICD shock. RESULTS: This meta-analysis comprised nine studies with a total of 5117 participants. Our study revealed that high levels of NT-pro BNP were associated with all-cause mortality (HR=2.12 (95% CI=1.53 to 2.93); p<0.001, I2=78.1%, p<0.001 for heterogeneity) and appropriate ICD shock (HR=1.71 (95% CI=1.18 to 2.49); p<0.001, I2=43.4%, p=0.102 for heterogeneity). The adjusted HR for all-cause mortality and appropriate ICD shock increased by approximately 3% and 5%, respectively per 100 pg/mL increment pursuant to concentration-response model (Pnon-linearity <0.001). The curves became steeper after NT-pro BNP reached its inflection point (3000 pg/mL). CONCLUSION: A positive concentration-dependent association between elevated NT-pro BNP levels along with the risk of all-cause mortality and appropriate ICD shock was found in patients with HFrEF with ICD. PROSPERO REGISTRATION NUMBER: CRD42022339285.

Warfarin Usage in Patients With Atrial Fibrillation Undergoing Hemodialysis in Indonesian Population.

The data about the efficacy and safety of warfarin usage in atrial fibrillation (AF) in hemodialysis patients is still limited, especially in the Asia population. The population of this study was end-stage renal disease patients with AF who underwent hemodialysis. The design of the study was a retrospective observational cohort that collected the patient data from 2016 to 2019. The Cox regression model was applied to assess the effect of warfarin on the outcomes. We conducted a survival analysis by comparing Kaplan-Meier curves using the log-rank test. We also measured the time in therapeutic range as a quality indicator of warfarin usage. Among 444 hemodialysis patients, 126 patients with AF matched the inclusion criteria, 88 patients completely followed up. Half patients used warfarin. The mean age was 52.2 ± 12.97 years, the mean follow-up duration was 11 ± 10 months. We observed all-cause death in 86.4% of patients, ischemic stroke in 10.2%, and hemorrhagic stroke in 2.3% of patients. There were no significant differences in all-cause death, ischemic stroke, and hemorrhagic stroke. Warfarin use was not associated with a lower rate for death (HR 0.782; 95% CI, 0.494-1.237, P = 0.293) or ischemic stroke (HR 0.435; 95% CI, 0.103-1.846, P = 0.259) or hemorrhagic stroke (HR 0.564; 95% CI, 0.034-9.386, P = 0.689). None of the patients reach the time in the therapeutic range >65%. Our findings suggest that warfarin has no association with mortality, ischemic stroke, and hemorrhagic stroke events rate in atrial fibrillation patients who underwent hemodialysis in the Indonesian population.

Left Volume Atrial Index and P-wave Dispersion as Predictors of Postoperative Atrial Fibrillation After Coronary Artery Bypass Graft: A Retrospective Cohort Study.

Preoperative left atrial remodeling as Postoperative atrial fibrillation (POAF) predisposing factors could be measured by left atrial volume index (LAVI) and P-wave dispersion. This study aimed to assess P-wave dispersion and LAVI as preoperative predictors of POAF among patients who underwent Coronary Artery Bypass Graft (CABG). An analytical retrospective cohort study was performed on patients who underwent CABG. The P-wave dispersion and POAF were evaluated based on documented ECG results. LAVI size was collected from echocardiographic reports. Hazard ratios of P-wave dispersion and LAVI for POAF were analyzed using Cox proportional hazard model. A total of 42 subjects (57 ± 1 years) were included in this study. POAF occurred in 28.6% of patients at a median of 2 days after CABG. P-wave dispersion was significantly longer in patients in whom AF was developed (53.03 ± 3.82 ms vs 44.01 ± 1.98ms, p:0.028), while LAVI difference was not significant. The Cox proportional hazard model showed a significant association between P-wave dispersion and risk of POAF (HR 1.05, CI95%, 1.001-1.103; P = 0.048). There was no association between LAVI and risk of POAF (HR 1.003, CI 95%, 0.965-1.044; P = 0.864). P-wave dispersion is a predictor of POAF in patients who underwent CABG. Risk stratification using P-wave dispersion enables clinicians to identify high-risk patients before CABG surgery.

Evaluation of adverse drug reaction in patients warfarin therapy.

This research aimed to understand the adverse drug reaction (ADR) in heart disease outpatients who were administered warfarin at a hospital in Bandung city. The research was conducted using a cross-sectional design with an observational approach. Subsequently, data were collected from 74 patients who met the inclusion criteria. The causality assessment was made by the Naranjo Algorithm and the incidence of bleeding was classified based on the Bleedscore™. The result showed that the most common ADR were nausea, dizziness, stomach ache, ecchymosis, petechiae, bleeding in the mouth, melena, etc. Furthermore, the INR value was the most significant factor in the incidence of ADR. It was 6.445 using a value of P = 0.001 or a confidence interval of 95%. The most common side effect of warfarin in cardiac outpatients was superficial bleeding, followed by internal bleeding (melena). The INR value is the most significant factor in measuring the incidence of ADR.

Metabolically unhealthy phenotype in normal weight population and risk of mortality and major adverse cardiac events: A meta-analysis of 41 prospective cohort studies.

BACKGROUND AND AIMS: It is still debatable whether metabolic status in normal weight population increases the risk of mortality (all-cause mortality (ACM), cardiovascular mortality (CVM)) and major adverse cardiac events (MACE) as compared to the obese population. Therefore, this meta-analysis aims to evaluate the association of the metabolically unhealthy normal weight (MUH-NW) phenotype with all-cause mortality, cardiovascular mortality, and MACE in comparison to metabolically healthy obesity (MH-O), along with the association of metabolically unhealthy obesity (MUH-O) phenotype regarding the same outcomes compared to MUH-NW. METHODS: A systematic literature search was conducted using online databases from inception to June 20, 2022, to comprehensively search all prospective cohort studies comprising three variables including adults aged ≥18 years, obesity and four metabolic phenotypes, and interest outcomes (ACM, CVM, and MACE). RESULTS: Forty-one prospective cohort studies with a total of 4,028,750 participants was included in this study. Compared to MH-O, MUH-NW had a substantially higher risk of ACM (RR = 1.47 (95%CI = 1.32-1.64); P < 0.001; I2 = 89.8%,P-heterogeneity<0.001), CVM (RR = 2.37 (95%CI = 1.97-2.86); P < 0.001; I2 = 83.7%,P-heterogeneity<0.001), and MACE (RR = 1.73 (95%CI = 1.49-2.00); P < 0.001; I2 = 74.3%,P-heterogeneity<0.001). Moreover, MUH-O did not have a significantly elevated risk of ACM (RR = 0.97 (95%CI = 0.82-1.15); P = 0.736; I2 = 98.3%,P-heterogeneity<0.001), CVM (RR = 0.96 (95%CI = 0.88-1.05); P = 0.394; I2 = 77.0%,P-heterogeneity<0.001), and MACE (RR = 0.95 (95%CI = 0.80-1.13); P = 0.570; I2 = 92.2%,P-heterogeneity<0.001) compared to MUH-NW. CONCLUSION: In conclusion, MUH-NW was superior but not inferior to MH-O and MUH-O in terms of increased risk of interest outcomes, refuting the notion that normal weight population is a benign condition. Hence, in normal weight population, metabolic screening is highly suggested to measure the baseline of obesity and metabolic phenotypes, thus preventing the risk of CVD and mortality in the future.

How Electronic Cigarette Affects the Vascular System.

The popularity of the electronic cigarette has soared in the last decades. However, the health effect of smoking electronic cigarettes on the vascular system is unclear. This systematic review examines the electronic cigarettes' effect on the vascular system from recent evidence. A systematic search was conducted in MEDLINE (PubMed) database from January 2016 to August 2021 for studies assessing the vascular effect of chronic use of electronic cigarettes on human and animal. The Cochrane Risk of Bias 2, NIH Quality Assessment for Cross-Sectional Study, and SYRCLE's Risk of Bias were used to assess the risk of bias in interventional, observational, and animal study, respectively. A narrative synthesis of evidence is provided to describe results. From 101 retrieved studies related to electronic cigarettes effect on the vascular system, a total of 16 studies are included in this review. The overall results indicated that electronic cigarette use is associated with adverse events in the vascular, including the incident of elevated oxidative stress, endothelial dysfunction, inflammation, arterial stiffness, and the development of atherosclerotic lesion. Further studies should broaden perspectives and reveal more about the mechanism of how electronic cigarettes impact on vascular system.

Revisiting exercise-induced premature ventricular complexes as a prognostic factor for mortality in asymptomatic patients: A systematic review and meta-analysis.

Background: Recent investigations suggest that premature ventricular complexes (PVCs) during an exercise test are associated with an elevated risk of mortality in asymptomatic individuals. However, given the small number of studies included, the association between these two entities in the asymptomatic population remains obscure. Our aim was to evaluate this matter. Methods: A comprehensive literature search was conducted utilizing several online databases up to April 2022. The study comprised cohort studies examining the relationship between exercise-induced premature ventricular complexes (EI-PVCs) and all-cause mortality (ACM) as well as cardiovascular mortality (CVM) in asymptomatic populations. To provide diagnostic values across the statistically significant parameters, we additionally calculated sensitivity, specificity, and area under the curve (AUC). Results: A total of 13 studies consisting of 82,161 patients with a mean age of 49.3 years were included. EI-PVCs were linked to an increased risk of ACM (risk ratio (RR) = 1.30 (95% confidence interval (CI) = 1.18-1.42); p < 0.001; I 2 = 59.6%, p-heterogeneity < 0.001) and CVM (RR = 1.67 (95% CI = 1.40-1.99); p < 0.001; I 2 = 7.5%, p-heterogeneity = 0.373). Subgroup analysis based on the frequency of PVCs revealed that frequent PVCs were similarly related to a higher risk of ACM and CVM, but not infrequent PVCs. Moreover, diagnostic test accuracy meta-analysis showed that recovery phase EI-PVCs have a higher overall specificity than exercise phase EI-PVCs regarding our outcomes of interest. Conclusion: EI-PVCs are correlated with a higher risk of ACM and CVM. When compared to the exercise phase, the specificity of PVCs generated during the recovery period in predicting interest outcomes is higher. As a result, we propose that the exercise ECG be utilized on a regular basis in middle-aged asymptomatic individuals to measure the frequency of PVCs and stratify the risk of mortality. Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=328852], identifier [CRD42022328852].

Electrocardiographic Markers Indicating Right Ventricular Outflow Tract Conduction Delay as a Predictor of Major Arrhythmic Events in Patients With Brugada Syndrome: A Systematic Review and Meta-Analysis.

Introduction: Risk stratification in Brugada Syndrome (BrS) patients is still challenging due to the heterogeneity of clinical presentation; thus, some additional risk markers are needed. Several studies investigating the association between RVOT conduction delay sign on electrocardiography (ECG) and major arrhythmic events (MAE) in BrS patients showed inconclusive results. This meta-analysis aims to evaluate the association between RVOT conduction delay signs presented by aVR sign and large S wave in lead I, and MAE in BrS patients. Methods: The literature search was performed using several online databases from the inception to March 16th, 2022. We included studies consisting of two main components, including ECG markers of RVOT conduction delay (aVR sign and large S wave in lead I) and MAE related to BrS (syncope/VT/VF/SCD/aborted SCD/appropriate ICD shocks). Results: Meta-analysis of eleven cohort studies with a total of 2,575 participants showed RVOT conduction delay sign was significantly associated with MAE in BrS patients [RR = 1.87 (1.35, 2.58); p < 0.001; I 2= 52%, P heterogeneity = 0.02]. Subgroup analysis showed that aVR sign [RR = 2.00 (1.42, 2.83); p < 0.001; I 2= 0%, P heterogeneity = 0.40] and large S wave in lead I [RR = 1.74 (1.11, 2.71); p = 0.01; I 2= 60%, P heterogeneity = 0.01] were significantly associated with MAE. Summary receiver operating characteristics analysis revealed the aVR sign [AUC: 0.77 (0.73-0.80)] and large S wave in lead I [AUC: 0.69 (0.65-0.73)] were a good predictor of MAE in BrS patients. Conclusion: RVOT conduction delay sign, presented by aVR sign and large S wave in the lead I, is significantly associated with an increased risk of MAE in BrS patients. Hence, we propose that these parameters may be useful as an additional risk stratification tool to predict MAE in BrS patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#recordDetails, identifier: CRD42022321090.