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.

Anemia and Poor Iron Indices Are Associated With Susceptibility to Febrile Seizures in Children: A Systematic Review and Meta-analysis.

Introduction: Febrile seizures are the most common type of seizure in children under the age of 5, and a number of risk factors for this condition have been identified. Several studies have examined the connection between iron deficiency anemia and febrile seizures in children, with inconsistent results. As a result, the authors sought to determine the precise link between iron deficiency anemia and its indices (mean corpuscular volume, serum iron, total iron-binding capacity, and ferritin) in conjunction to febrile seizures. Methods: A systematic literature search from several databases (PubMed, Europe PMC, ScienceDirect) was conducted from database inception until November 30, 2022. Studies were eligible if they investigated the relationship of the iron deficiency anemia and the aforementioned indices with the likelihood of febrile seizures. Results: This meta-analysis comprised 20 case-control studies with a total of 3856 participants. Our study revealed that iron deficiency anemia, low mean corpuscular volume, low serum iron, high total iron-binding capacity, and low ferritin were associated with the incremental risk of developing febrile seizures, with the odds ratios ranging from 1.24 to 1.59. Moreover, diagnostic test accuracy meta-analysis indicated that low serum ferritin level had the highest overall area under the curve value amid other iron deficiency anemia indices regarding our outcomes of interest. Conclusion: This study suggest that iron deficiency anemia and poor iron indices are associated with increased risk of febrile seizures in children.

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.

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.

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].

Association of Admission Time and Mortality in STEMI Patients: A Systematic Review and Meta-analysis.

This systematic review and meta-analysis aimed to evaluate patients with acute ST-segment elevation myocardial infarction (STEMI) who were admitted during off-hours and treated with primary angioplasty associated with an increased risk of mortality compared with those admitted during regular working hours. We performed a systematic literature search using PubMed, SCOPUS, Europe PMC, and Cochrane CENTRAL databases that was finalized on March 15, 2021. The primary outcome was mortality comprising early (in-hospital), midterm (30 days to 1 year), and long-term mortality (>1 year). A total of 384,452 patients from 56 studies were included. The overall mortality of acute STEMI patients admitted during off-hours and regular hours were 6.1 and 6.7%, respectively. Patients admitted during off-hours had similar risk of early, midterm, and long-term mortality compared to those admitted during regular working hours ([relative risk or RR = 1.07, 95% confidence interval or CI, 1.00-1.14, p = 0.06; I 2 = 45%, p = 0.0009], [RR = 1.00, 95% CI, 0.95-1.05, p = 0.92; I 2 = 13%, p = 0.26], and [RR = 0.95, 95% CI, 0.86-1.04, p = 0.26; I 2 = 0%, p = 0.76], respectively). Subgroup analyses indicated that the results were consistent across all subgroups ([women vs. men], [age >65 years vs. ≤65 years], and [Killip classification II to IV vs. Killip I]). Funnel plot was asymmetrical. However, Egger's test suggests no significance of small-study effects ( p = 0.19). This meta-analysis showed that patients with acute STEMI who were admitted during off-hours and treated with primary angioplasty had similar risk of early, midterm, and long-term mortality compared with those admitted during regular working hours.

Pentraxin 3 concentration is associated with poor outcomes in patients with coronary artery disease: a systematic review and dose-response meta-analysis.

BACKGROUND: The amount of plasma pentraxin 3 (PTX3) is gradually being considered as a novel biomarker in forecasting poor clinical outcomes in patients with coronary artery disease (CAD). However, very little is known about the connection between PTX3 and CAD. This dose-response meta-analysis was carried out to quantify the relationship between circulating PTX3 concentration and CAD prognosis. METHODS: A systematic literature search was conducted using PubMed, EuropePMC, ProQuest, EBSCOhost, SCOPUS, Cochrane Library, and Google Scholar up until April 2021. The primary outcome of this study consisted of mortality and major adverse cardiovascular events (MACEs). RESULTS: The current meta-analysis comprised 15 studies with a total of 11.365 participants. High circulating PTX3 concentrations were associated with a higher risk of composite poor outcomes as compared to low circulating PTX3 concentrations (OR: 1.36 [1.18, 1.54], p < 0.001; I2 = 86.69%, Pheterogeneity<0.001), mortality (OR: 1.43 [1.15, 1.71], p < 0.001; I2 = 87.58%, Pheterogeneity<0.001), and MACEs (OR: 1.28 [1.08, 1.48], p < 0.001; I2 = 35.86%, Pheterogeneity = 0.08) in patients with CAD. Consistent results were obtained during meta-regression analyses and in all examined subgroups. The adjusted odds ratios (aORs) for composite poor outcomes increased by 32% per 1 ng/mL increment (OR: 1.32 [1.21, 1.43]) in line with the dose-response meta-analysis. CONCLUSION: A significant positive dose-dependent association between circulating PTX3 concentration and the risk of poor outcomes in patients with CAD was found in this dose-response meta-analysis.

Investigating the implications of COVID-19 outbreak on systems of care and outcomes of STEMI patients: A systematic review and meta-analysis.

INTRODUCTION: There has been a concern whether the decrease in ST-segment elevation myocardial infarction (STEMI) cases during the COVID-19 pandemic era is related to unsatisfactory performance of STEMI systems of care as well as worsening of the clinical outcomes in STEMI patients. Thus, our meta-analysis was conducted to evaluate this matter. METHODS: We compared the predetermined variables in this meta-analysis during the early and late pandemic. Using a combination of adapted search terms to fit the requirements of several search engines (PubMed, EuropePMC, SCOPUS, ProQuest, and EBSCOhost), we reviewed all observational studies citing our outcomes of interest before and during the outbreak. RESULTS: Thirty-five records comprising a total of 62,247 participants were identified. Overall, our meta-analysis showed that there was a huge reduction of nearly 80% for STEMI admission during the outbreak (n = 10,263) in contrast to before the outbreak period (n = 51,984). STEMI patients who were admitted during the outbreak received less primary PCI and had longer symptom-to-FMC (first medical contact) time along with prolonged door-to-balloon (DTB) time. A decrease in the achievement of final TIMI (thrombolysis in myocardial infarction) 3 flow after primary PCI was also observed in this study. However, the number of in-hospital mortality was similar between two groups. CONCLUSION: There was a decrease in the STEMI care performance and worsening of clinical outcomes in STEMI patients, especially in the early pandemic period. Overall, concise health services must be implemented following a responsibility to obey health protocols to deliver high-quality services related to STEMI systems of care amidst the global pandemic.

Corticosteroid Therapy in Management of Myocarditis Associated with COVID-19; a Systematic Review of Current Evidence.

INTRODUCTION: Myocarditis in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seems to be associated with a higher mortality rate. This study aims to summarize the latest evidence on whether the use of corticosteroids in patients with myocarditis associated with COVID-19 is necessary. METHODS: We performed an extensive search using a combination of search terms in PubMed, Europe PMC, ProQuest, EBSCOhost, and Google Scholar up to January 2021. Full-text articles that met the predefined inclusion criteria were included in the present study. RESULTS: The full-texts of 18 articles have been reviewed. Thirteen out of the eighteen (72%) patients who got corticosteroid administration experienced major clinical improvements during follow-up while the other five (28%) were experiencing uneventful events. The mean age of the reported patients was 47.8±13.2 years. There was no gender predominance. Most of the reported cases were from USA (39%) followed by Spain, China, and UK (11% each), while Brazil, Colombia, France, Belgium, and Italy contributed one case each. Various corticosteroids were used but the most commonly applied were methylprednisolone (89%), hydrocortisone (5.5%), and prednisolone (5.5%). The most common route of administration among the studies was intravenous administration and the duration of treatment varied between one and fourteen days. CONCLUSION: A review of the currently available literature shows that with the use of corticosteroid agents in treating myocarditis associated with COVID-19, favorable outcomes are attainable. Well-established randomized clinical trials are needed to evaluate the efficacy and safety of using corticosteroids in this condition.