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.

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.

Novel scoring system based on clinical examination for prediction of in-hospital mortality in acute coronary syndrome patients: a retrospective cohort study.

BACKGROUND: This study aims to develop PADjadjaran Mortality in Acute coronary syndrome (PADMA) Score to predict in-hospital mortality in acute coronary syndrome (ACS) patients based on clinical examination only. Additionally, we also compared the predictive value of the PADMA Score with the Global Registry of Acute Coronary Events (GRACE), Canada Acute Coronary Syndrome (C-ACS), and The Portuguese Registry of Acute Coronary Syndromes (ProACS) risk scores. METHODS: This retrospective cohort study included all ACS patients aged≥18 years who were admitted to Dr. Hasan Sadikin Central General Hospital from January 2018 to January 2022. Patients' demographic, comorbidities and clinical presentation data were collected and analysed using multivariate logistic regression to create two models of scoring system (probability and cut-off model) to predict in-hospital all-cause mortality. The area under the curve (AUC) among PADMA, GRACE, C-ACS and ProACS risk scores was compared using the fisher Z test. RESULTS: Multivariate regression analysis of 1359 patients showed that older age, history of cerebrovascular disease, tachycardia, high Shock Index and Killip class III and IV were independent mortality predictors and included in the PADMA Score. PADMA Score ranged from 0 to 20, with a score≥5 that can predict all-cause mortality with 82.78% sensitivity and 72.35% specificity. The difference in AUC between PADMA and GRACE scores was insignificant (p=0.126). Moreover, the AUC of the PADMA Score was significantly higher compared with the C-ACS (p=0.002) and ProACS risk scores (p<0.001). CONCLUSION: PADMA Score is a simple scoring system to predict in-hospital mortality in ACS patients. PADMA Score≥5 showed an accurate discriminative capability to predict in-hospital mortality, comparable with the GRACE Score and superior to C-ACS and ProACS scores.

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.

Managing Covid-19 in patients with heart failure: current status and future prospects.

INTRODUCTION: COVID-19 may contribute to decompensation of previously stable chronic HF or cause a de-novo heart failure, which may come from the hyperinflammatory response and subsequent increase in metabolic demand. AREAS COVERED: Two independent investigators searched MEDLINE (via PubMed), Europe PMC, and ScienceDirect databases with the following search terms: COVID-19, heart failure, COVID-19 drugs, heart failure drugs, and device therapy. All of the included full-text articles were rigorously evaluated by both authors in case there was disagreement about whether research should be included or not. In total, 157 studies were included and underwent extensive reading by the authors. EXPERT OPINION: The World Health Organization (WHO) and the National Institute of Health (NIH) have published COVID-19 drug recommendations, although recommendations for HF-specific drug choices in COVID-19 are still lacking. We hope that this review can answer the void of comprehensive research data regarding the management options of HF in the COVID-19 condition so that clinicians can at least choose a more beneficial therapy or avoid combination therapies that have a high burden of side effects on HF; thus, morbidity and mortality in COVID-19 patients with HF may be reduced.

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.

Modified Shock Index as Simple Clinical Independent Predictor of In-Hospital Mortality in Acute Coronary Syndrome Patients: A Retrospective Cohort Study.

Introduction: Despite being the current most accurate risk scoring system for predicting in-hospital mortality for patients with acute coronary syndrome (ACS), the Global Registry of Acute Coronary Events (GRACE) risk score is time consuming due to the requirement for electrocardiography and laboratory examinations. This study is aimed to evaluate the association between modified shock index (MSI), as a simple and convenient index, with in-hospital mortality and revascularization in hospitalized patients with ACS. Methods: A single-centered, retrospective cohort study, involving 1,393 patients with ACS aged ≥ 18 years old, was conducted between January 2018 and January 2022. Study subjects were allocated into two cohorts: high MSI ≥ 1 (n = 423) and low MSI < 1 group (n = 970). The outcome was in-hospital mortality and revascularization. The association between MSI score and interest outcomes was evaluated using binary logistic regression analysis. The area under the curve (AUC) between MSI and GRACE score was compared using De Long's method. Results: Modified shock index ≥ 1 had 61.1% sensitivity and 73.7% specificity. A high MSI score was significantly and independently associated with in-hospital mortality in patients with ACS [odds ratio (OR) = 2.72(1.6-4.58), p < 0.001]. However, ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) patients with high MSI did not significantly increase the probability of revascularization procedures. Receiver operating characteristic (ROC) analysis demonstrated that although MSI and GRACE scores were both good predictors of in-hospital mortality with the AUC values of 0.715 (0.666-0.764) and 0.815 (0.775-0.855), respectively, MSI was still inferior as compared to GRACE scores in predicting mortality risk in patients with ACS (p < 0.001). Conclusion: Modified shock index, particularly with a score ≥ 1, was a useful and simple parameter for predicting in-hospital mortality in patients presenting with ACS.

Pre-pregnancy obesity and the risk of peripartum cardiomyopathy: A systematic review and meta-analysis.

The outcome of this review is to assess the association between pre-pregnancy obesity and PPCM incidence. There were a total of 5.373.581 participants were included in this study. Pre-pregnancy obesity was significantly associated with PPCM incidence compared to normal-weight subjects (OR = 1.79 (1.16,2.76); p = 0.008; I2 = 59%, Pheterogeneity = 0.04). The sub-group analysis showed that pre-pregnancy women with obesity class I (OR = 1.58 (1.20,2.07); p = 0.001; I2 = 0%, Pheterogeneity = 0.64) and class II and III (OR = 2.65 (2.04,3.45); p < 0.001; I2 = 6%, Pheterogeneity = 0.36) was significantly associated with PPCM incidence compared to normal-weight subjects.

Cardiometabolic risk factors in adults with normal weight obesity: A systematic review and meta-analysis.

Normal weight obesity (NWO) is a new emerging phenotype of obesity, defined as a normal body mass index with a high body fat percentage. While several studies have described the impact of NWO on cardiometabolic risk factors, the association between them remains uncertain. This meta-analysis systematically evaluated cardiometabolic risk factors in adults with NWO compared to adults with normal weight lean (NWL). A systematic literature search was performed from the inception until September 21, 2021 in order to comprehensively search for all observational studies that had three important variables, including adults (age ≥18 years old), NWO and cardiometabolic risk factors including metabolic syndrome, hypertension, diabetes mellitus, dyslipidaemia or all laboratory findings related to cardiometabolic risk factors. Twenty-four cross-sectional studies with a total of 75 201 subjects are included in the qualitative and quantitative analysis. Overall, older age and female sex are more likely in NWO population. Compared to NWL, NWO is significantly associated with cardiometabolic risk factors, including metabolic syndrome (OR = 2.24 [1.74, 2.89]; p < .001; I2  = 76%, Pheterogeneity < 0.001), hypertension (OR = 1.60[1.36, 1.89]; p < .001; I2  = 76%, Pheterogeneity < 0.001), diabetes mellitus (OR = 1.72[1.54, 1.92]; p < .001; I2  = 47%, Pheterogeneity < 0.001), dyslipidaemia (OR = 1.50 [1.03, 2.18]; p = .03; I2  = 94%, Pheterogeneity < 0.001) and other laboratory findings, except for C-reactive protein in both sexes group; and adiponectin levels in female group. Our meta-analysis showed that NWO was associated with cardiometabolic risk factors. Thus, the traditional definition of obesity using the BMI criteria should be challenged, as those with NWO might still be exposed to a heightened risk of cardiometabolic disorders. Nonetheless, further prospective cohort studies are needed better to understand this syndrome.

Chronic Heart Failure: Clinical Implications of Iron Homeostasis Disturbances Revisited.

Iron deficiency is prevalent in chronic heart failure (CHF) patients. Nonetheless, the diagnosis is often overlooked and, often, the treatment is commenced just when overt anemia has ensued. Therefore, a better appreciation of this disease is needed, and all seasoned cardiologists should know how to approach CHF patients with iron deficiency correctly, as mandated by clinical practice guidelines. In this comprehensive review, we describe iron homeostasis, the pathophysiologic changes of iron homeostasis, and the clinical implications of iron deficiency on CHF patients. In addition, we delineate the evolution of clinical trials, ranging from the inception to the ongoing clinical trials of iron deficiency treatment in CHF patients. Iron deficiency contributes to the worse clinical outcome of the patients. Numerous studies have reported the clinical benefit of iron supplementation, particularly in intravenous preparation, in heart failure patients regarding symptoms, functional capacity, and quality of life (QoL) improvement. Therefore, the current guidelines recommend routine screening of iron status in all newly diagnosed heart failure patients. Eventually, intravenous iron replacement is recommended for symptomatic heart failure patients with iron deficiency, irrespective of anemia.

Cardiac manifestations, treatment characteristics, and outcomes of paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2: A systematic review.

BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) temporally associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (PIMS-TS) is a rare clinical syndrome associated with a multiorgan system dysfunction, especially acute cardiac injury, and mandates a higher level of care. AIM OF REVIEW: To investigate cardiac manifestations, treatment characteristics, and outcomes of PIMS-TS. KEY SCIENTIFIC CONCEPTS OF REVIEW: Twenty-six studies were included with 1228 pooled subjects, with a mean age of 8.6 years, which were dominated by male gender (53%), and African ethnicity (31%). 732 (38%) patients were reactive on a serological test, and 457 patients (45%) were positive on SARS-CoV-2 RT-PCR. ST-segment abnormalities were the most common ECG findings (16%, n/N: 34/212). Various markers of troponin and the pooled mean of BNP and NT-pro-BNP levels were elevated. Cardiomegaly and pericardial effusion (21.8%, n/N: 164/751) were the most common chest X-ray findings. In echocardiography, the majority of patients' left ventricular ejection fraction was reduced (59.0%, n/N: 180/305), with pericardial effusion/ pericarditis seen the most (17.44%, n/N: 221/1267), and Z score ≥ 2 in 28% (n/N: 42/139). Cardiac MRI findings were consistent with acute myocarditis. Intravenous immunoglobulin, corticosteroids, and vasoactive drugs were frequently utilized. The mean length of stay was 6 days, with most patients (71%, n/N: 834/1163) were admitted to the ICU. However, the overall prognosis was favorable, with 98% alive (n/N: 1235/1260), and more than 50% of patients experienced recovery of left ventricular systolic functions at discharge (116 out of 206 patients).

Coronavirus Disease of 2019: a Mimicker of Dengue Infection?

At the beginning of 2020, the national health system and medical communities are faced with unprecedented public health challenges. A novel strain of coronavirus, later identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, marking another pandemic of coronaviruses. This viral disease is responsible for devastating pneumonia, named coronavirus disease of 2019 (COVID-19), and projected to persist until the end of the year. In tropical countries, however, concerns arise regarding the similarities of COVID-19 with other infectious diseases due to the same chief complaint, which is fever. One of the infectious disease of a primary concern is dengue infection, which its peak season is approaching. Others report that there are cases of serological cross-reaction of COVID-19 and dengue infection. In this comprehensive review, we underscore the importance of knowing similar clinical presentations of both diseases and emphasize why excluding COVID-19 in the differentials in the setting of a pandemic is imprudent.