A Territory-Wide Study of Arrhythmogenic Right Ventricular Cardiomyopathy Patients from Hong Kong.

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a hereditary disease characterized by fibrofatty infiltration of the right ventricular myocardium that predisposes affected patients to malignant ventricular arrhythmias, dual-chamber cardiac failure and sudden cardiac death (SCD). The present study aims to investigate the risk of detrimental cardiovascular events in an Asian population of ARVC/D patients, including the incidence of malignant ventricular arrhythmias, new-onset heart failure with reduced ejection fraction (HFrEF), as well as long-term mortality. Methods and Results: This was a territory-wide retrospective cohort study of patients diagnosed with ARVC/D between 1997 and 2019 in Hong Kong. This study consisted of 109 ARVC/D patients (median age: 61 [46-71] years; 58% male). Of these, 51 and 24 patients developed incident VT/VF and new-onset HFrEF, respectively. Five patients underwent cardiac transplantation, and 14 died during follow-up. Multivariate Cox regression identified prolonged QRS duration as a predictor of VT/VF (p < 0.05). Female gender, prolonged QTc duration, the presence of epsilon waves and T-wave inversion (TWI) in any lead except aVR/V1 predicted new-onset HFrEF (p < 0.05). The presence of epsilon waves, in addition to the parameters of prolonged QRS duration and worsening ejection fraction predicted all-cause mortality (p < 0.05). Clinical scores were developed to predict incident VT/VF, new-onset HFrEF and all-cause mortality, and all were significantly improved by machine learning techniques. Conclusions: Clinical and electrocardiographic parameters are important for assessing prognosis in ARVC/D patients and should in turn be used in tandem to aid risk stratification in the hospital setting.

Diagnostic and prognostic value of serum C-reactive protein in heart failure with preserved ejection fraction: a systematic review and meta-analysis.

Heart failure (HF) is a major epidemic with rising morbidity and mortality rates that encumber global healthcare systems. While some studies have demonstrated the value of CRP in predicting (i) the development of HFpEF and (ii) long-term clinical outcomes in HFpEF patients, others have shown no such correlation. As a result, we conducted the following systematic review and meta-analysis to assess both the diagnostic and prognostic role of CRP in HFpEF. PubMed and Embase were searched for studies that assess the relationship between CRP and HFpEF using the following search terms: (((C-reactive protein) AND ((preserved ejection fraction) OR (diastolic heart failure))). The search period was from the start of database to August 6, 2019, with no language restrictions. A total of 312 and 233 studies were obtained from PubMed and Embase respectively, from which 19 studies were included. Our meta-analysis demonstrated the value of a high CRP in predicting the development of not only new onset HFpEF (HR: 1.08; 95% CI: 1.00-1.16; P = 0.04; I2 = 22%), but also an increased risk of cardiovascular mortality when used as a categorical (HR: 2.52; 95% CI: 1.61-3.96; P < 0.0001; I2 = 19%) or a continuous variable (HR: 1.24; 95% CI: 1.04-1.47; P = 0.01; I2 = 28%), as well as all-cause mortality when used as a categorical (HR: 1.78; 95% CI: 1.53-2.06; P < 0.00001; I2 = 0%) or a continuous variable: (HR: 1.06; 95% CI: 1.02-1.06; P = 0.003; I2 = 61%) in HFpEF patients. CRP can be used as a biomarker to predict the development of HFpEF and long-term clinical outcomes in HFpEF patients, in turn justifying its use as a simple, accessible parameter to guide clinical management in this patient population. However, more prospective studies are still required to not only explore the utility and dynamicity of CRP in HFpEF but also to determine whether risk stratification algorithms incorporating CRP actually provide a material benefit in improving patient prognosis.

Takotsubo cardiomyopathy with low ventricular ejection fraction and apical ballooning predicts mortality: a systematic review and meta-analysis.

Takotsubo cardiomyopathy (TCM) is characterized by temporary wall motion abnormality of the left ventricle. There is much debate upon the prognostic parameters. We conducted a systematic review and meta-analysis to investigate whether LVEF and the presence of apical ballooning predict long-term mortality in TCM. PubMed and Embase were searched through to October 30, 2017 without language restrictions, followed by an additional search through to February 2, 2020. Our search identified 18 studies that met the inclusion criteria, with a total of 5168 patients. Reduced LVEF as a categorical variable was associated with more than threefold increase in mortality risk in TCM patients (HR 3.10; 95% CI 1.78-5.42; P < 0.0001; I2 = 57%). Further subset analyses with the exclusion of studies consisting of patients with coronary artery disease revealed another significant relationship between LVEF and mortality (HR 3.13; 95% CI 1.392-7.031; P < 0.006; I2 = 58%). LVEF as a continuous variable was also found to be associated with increased mortality risk. However, this relationship only retained significance when computing odds ratios instead of hazard ratios (OR 0.95; 95% CI 0.93-0.98; P < 0.001; I2 = 0%). Finally, the existence of apical ballooning failed to demonstrate any link with an increased risk of mortality (HR 1.26; 95% CI 0.97-1.64; P = 0.09; I2 = 34%). LVEF and apical ballooning are both potential prognostic markers for mortality.

Comparative cardiovascular risk in users versus non-users of xanthine oxidase inhibitors and febuxostat versus allopurinol users.

OBJECTIVES: The aim of this study is to determine major adverse cardiovascular events (MACE) and all-cause mortality comparing between xanthine oxidase inhibitors (XOIs) and non-XOI users, and between allopurinol and febuxostat. METHODS: This is a retrospective cohort study of gout patients prescribed anti-hyperuricemic medications between 2013 and 2017 using a territory-wide administrative database. XOI users were matched 1:1 to XOI non-users using propensity scores. Febuxostat users were matched 1:3 to allopurinol users. Subgroup analyses were conducted based on colchicine use. RESULTS: Of the 13 997 eligible participants, 3607 (25.8%) were XOI users and 10 390 (74.2%) were XOI non-users. After propensity score matching, compared with non-users (n = 3607), XOI users (n = 3607) showed similar incidence of MACE (hazard ratio [HR]: 0.997, 95% CI, 0.879, 1.131; P>0.05) and all-cause mortality (HR = 0.972, 95% CI 0.886, 1.065, P=0.539). Febuxostat (n = 276) users showed a similar risk of MACE compared with allopurinol users (n = 828; HR: 0.672, 95% CI, 0.416, 1.085; P=0.104) with a tendency towards a lower risk of heart failure-related hospitalizations (HR = 0.529, 95% CI 0.272, 1.029; P=0.061). Concurrent colchicine use reduced the risk for all-cause mortality amongst XOI users (HR = 0.671, 95% 0.586, 0.768; P<0.001). CONCLUSION: In gout patients, XOI users showed similar risk of MACE and all-cause mortality compared with non-users. Compared with allopurinol users, febuxostat users showed similar MACE and all-cause mortality risks but lower heart failure-related hospitalizations.

Multi-parametric system for risk stratification in mitral regurgitation: A multi-task Gaussian prediction approach.

BACKGROUND: We hypothesized that a multi-parametric approach incorporating medical comorbidity information, electrocardiographic P-wave indices, echocardiographic assessment, neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) calculated from laboratory data can improve risk stratification in mitral regurgitation (MR). METHODS: Patients diagnosed with mitral regurgitation between 1 March 2005 and 30 October 2018 from a single centre were retrospectively analysed. Outcomes analysed were incident atrial fibrillation (AF), transient ischemic attack (TIA)/stroke and mortality. RESULTS: This study cohort included 706 patients, of whom 171 had normal inter-atrial conduction, 257 had inter-atrial block (IAB) and 266 had AF at baseline. Logistic regression analysis showed that age, hypertension and mean P-wave duration (PWD) were significant predictors of new-onset AF. Low left ventricular ejection fraction (LVEF), abnormal P-wave terminal force in V1 (PTFV1) predicted TIA/stroke. Age, smoking, hypertension, diabetes mellitus, hypercholesterolaemia, ischemic heart disease, secondary mitral regurgitation, urea, creatinine, NLR, PNI, left atrial diameter (LAD), left ventricular end-diastolic dimension, LVEF, pulmonary arterial systolic pressure, IAB, baseline AF and heart failure predicted all-cause mortality. A multi-task Gaussian process learning model demonstrated significant improvement in risk stratification compared to logistic regression and a decision tree method. CONCLUSIONS: A multi-parametric approach incorporating multi-modality clinical data improves risk stratification in mitral regurgitation. Multi-task machine learning can significantly improve overall risk stratification performance.

Percutaneous Coronary Intervention Versus Medical Therapy for Chronic Total Occlusion of Coronary Arteries: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Chronic total occlusion (CTO) of the coronary arteries is a significant clinical problem and has traditionally been treated by medical therapy or coronary artery bypass grafting. Recent studies have examined percutaneous coronary intervention (PCI) as an alternative option. RECENT FINDINGS: This systematic review and meta-analysis compared medical therapy to PCI for treating CTOs. PubMed and Embase were searched from their inception to March 2019 for studies that compared medical therapy and PCI for clinical outcomes in patients with CTOs. Quality of the included studies was assessed by Newcastle-Ottawa scale. The results were pooled by DerSimonian and Laird random- or fixed-effect models as appropriate. Heterogeneity between studies and publication bias was evaluated by I2 index and Egger's regression, respectively. Of the 703 entries screened, 17 studies were included in the final analysis. This comprised 11,493 participants. Compared to PCI, medical therapy including randomized and observational studies was significantly associated with higher risk of all-cause mortality (risk ratio (RR) 1.99, 95% CI 1.38-2.86), cardiac mortality (RR 2.36 (1.97-2.84)), and major adverse cardiac event (RR 1.25 (1.03-1.51)). However, no difference in the rate of myocardial infarction and repeat revascularization procedures was observed between the two groups. Univariate meta-regression demonstrated multiple covariates as independent moderating factors for myocardial infarction and repeat revascularization but not cardiac death and all-cause mortality. However, when only randomized studies were included, there was no difference in overall mortality or cardiac death. In CTO, when considering randomized and observational studies, medical therapy might be associated with a higher risk of mortality and myocardial infarction compared to PCI treatment.

Electrocardiographic evidence of abnormal atrial phenotype in Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is an inherited ion channelopathy that may predispose affected individuals to atrial cardiomyopathy. We tested the hypothesis that BrS patients have higher degrees of atrial electrophysiological abnormalities compared to controls, and these can be reflected by changes in P-wave parameters determined on the electrocardiogram (ECG). METHODS: This was a single-center retrospective study comparing BrS patients to age- and gender-matched control subjects. Mean P-wave duration (PWDmean), maximum PWD (PWDmax) and minimum PWD (PWDmin), P-wave dispersion (PWDmax - PWDmin), and P-wave terminal force in V1 (PTFV1) were measured. PWDmax ≥ 120 ms, in the presence and absence of biphasic P-waves in the inferior leads, were termed advanced and partial inter-atrial block (IAB), respectively. RESULTS: The proportion of IAB was significantly higher in BrS patients (28/51; 55%) than in control subjects (14/51; 27%; Fisher's Exact test; P < 0.01). Advanced IAB was observed in two BrS patients but none of the control subjects (P = 0.50). Compared to controls, BrS patients showed higher PWDmean (107 [98-113] vs. 97 [90-108] ms; KWANOVA, P < 0.01), PWDmax (123 [110-132] vs. 113 [107-121] ms; P < 0.001) but statistically indistinguishable PWDmin (82 [72-92] vs. 77 [69-85]; P = 0.09), and P-wave dispersion (38 [26-52] vs. 37 [23-45] ms; P = 0.14). PTFV1 was significantly higher in BrS patients than in control subjects (24 [0-40] vs. 0 [0-27] mm.ms; P < 0.05). CONCLUSION: Atrial conduction abnormalities are frequently observed in BrS. These patients may require monitoring for future development of atrial fibrillation and stroke.

Electrographic indices in migraine patients: A systematic review and meta-analysis.

BACKGROUND AND AIM: Migraine patients can exhibit autonomic dysregulation, in turn leading to cardiac conduction and repolarization abnormalities. This systematic review and meta-analysis evaluated the electrocardiographic changes in migraineurs. METHOD: PubMed and Embase databases were searched for human studies using the search terms 'migraine' and 'electrocardiogram' until 15th December 2018, identifying 108 and 131 studies. RESULTS: Thirteen studies involving 667 migraineurs and 208 normal subjects included (mean age=30.7, total male percentage=19.8%) were included. A longer mean QTc interval (standard mean difference=7.89, 95% confidence interval=[3.29, 12.49], p=0.0008) and higher frequency of QTc prolongation (risk ratio [RR]=6.23, [2.86-13.58], p<0.00001), but no difference in PR-interval (SMD=4.33, [-3.90-12.56], p=0.30) were observed during migraine attacks compared to pain-free periods. P-wave dispersion was higher in migraine patients compared to controls (mean difference=3.62, [1.03-6.21], p=0.006). RR-interval were statistically indistinguishable between migraine patients and controls (SMD=0.08, [-0.65-0.81], p=0.83), or between migraineurs with and without aura (SMD=-0.03, [-0.44-0.38], p=0.89). Deep breathing ratio was significantly lower in migraineurs compared to controls (SMD=-0.27, 95% CI=[-0.46, -0.08], p=0.006) but similar between migraineurs with and without aura (SMD=-0.04, [-0.27-0.19], p=0.74). No significant difference in Valsalva ratio is found between migraineurs and controls (SMD=0.10, [-0.32-0.53], p=0.63) or between migraineurs with and without aura (SMD=-0.17, [-0.40-0.06], p=0.14). Root mean square of successive differences (RMSSD) (SMD=-0.07, [-1.10-0.95], p=0.89) and standard deviation of NN intervals (SDNN) (SMD=-0.10, [-0.61-0.41], p=0.71) did not significantly differ between migraine patients and controls. CONCLUSION: Electrocardiographic alterations are observed in migraine patients compared to controls, especially during migraine attacks.

Mouse models of atherosclerosis: a historical perspective and recent advances.

Atherosclerosis represents a significant cause of morbidity and mortality in both the developed and developing countries. Animal models of atherosclerosis have served as valuable tools for providing insights on its aetiology, pathophysiology and complications. They can be used for invasive interrogation of physiological function and provide a platform for testing the efficacy and safety of different pharmacological therapies. Compared to studies using human subjects, animal models have the advantages of being easier to manage, with controllable diet and environmental risk factors. Moreover, pathophysiological changes can be induced either genetically or pharmacologically to study the harmful effects of these interventions. There is no single ideal animal model, as different systems are suitable for different research objectives. A good understanding of the similarities and differences to humans enables effective extrapolation of data for translational application. In this article, we will examine the different mouse models for the study and elucidation of the pathophysiological mechanisms underlying atherosclerosis. We also review recent advances in the field, such as the role of oxidative stress in promoting endoplasmic reticulum stress, mitochondrial dysfunction and mitochondrial DNA damage, which can result in vascular inflammation and atherosclerosis. Finally, novel therapeutic approaches to reduce vascular damage caused by chronic inflammation using microRNA and nano-medicine technology, are discussed.

Spiked Helmet Electrocardiographic Sign-A Systematic Review of Case Reports.

First reported in 2011, the spiked helmet sign (SHS) is an electrocardiographic pattern of ST-segment elevation anecdotally associated with poor prognosis. This study aims to systematically evaluate the electrocardiographic characteristics, clinical presentations, and outcomes of all cases of SHS reported in the literature. PubMed, Scopus, Web of Science, and EMBASE were searched electronically from their inception until November 2022. The Joanna Briggs Institute Critical Appraisal Checklist for Case Reports was used to critically appraise included studies. Studies written in English describing at least one patient with SHS were included. Altogether, 26 case reports or series describing 39 patients with SHS were included. All included studies were rated of acceptable quality. Associated conditions were heterogeneous, with intracranial hemorrhagic complications being the most common (9 patients), followed by pneumothorax (6 patients) or severe pneumonia (4 patients), bowel ischemia or obstruction (6 patients), and autonomic dysfunction (3 patients with Takotsubo cardiomyopathy and 3 patients with spinal injury, cocaine overuse, and stellate gangliectomy). Two patients had multiple complications and 12 other patients suffered from sepsis, myocardial infarction, etc. Clinical outcomes were reported for 32 patients, of whom 19 (59%) died during hospitalization (6 patients with pneumothorax or pneumonia, 4 patients with intracranial hemorrhagic complications, 2 patients with bowel ischemia or obstruction, and 7 patients due to other reasons). SHS may be associated with poor prognosis, necessitating its prompt recognition by clinicians and swift evaluation for underlying causes. Larger studies are needed to elucidate its prevalence, clinical implications, and precipitating mechanisms.

Acute ischemic stroke management: concepts and controversies.A narrative review.

INTRODUCTION: Amongst the 25.7 million survivors and 6.5 million deaths from stroke between 1990 and 2013, ischemic strokes accounted for approximately 70% and 50% of the cases, respectively. With patients still suffering from complications and stroke recurrence, more questions have been raised as to how we can better improve patient management. AREAS COVERED: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Newcastle-Ottawa Scale (NOS) were adopted to ensure a comprehensive inclusion of quality literature from various sources. PubMed and Embase were searched for evidence on thrombolysis, mechanical thrombectomy, artificial intelligence (AI), antiplatelet therapy, anticoagulation and hypertension management. EXPERT OPINION: The directions of future research in these areas are dependent on the current level of validation. Endovascular therapy and applications of AI are relatively new compared to the other areas discussed in this review. As such, future studies need to focus on validating their efficacy. As for thrombolysis, antiplatelet and anticoagulation therapy, their efficacy has been well-established and future research efforts should be directed toward adjusting its use according to patient-specific factors, starting with factors with the most clinical relevance and prevalence.

Protective Effects of Sodium-Glucose Transporter 2 Inhibitors on Atrial Fibrillation and Atrial Flutter: A Systematic Review and Meta- Analysis of Randomized Placebo-Controlled Trials.

Background: Hyperglycemia is associated with an increased risk of developing atrial fibrillation (AF) and atrial flutter (AFL). Sodium-glucose transporter 2 inhibitors (SGLT2i) have been reported to prevent AF/AFL in some studies, but not others. Therefore, a meta-analysis was performed to investigate whether SGLT2i use is associated with lower risks of AF/AFL. Methods: PubMed, Scopus, Web of Science, Cochrane library databases were searched for randomized placebo-controlled trials comparing SGLT2i and placebo. Results: A total of 33 trials involving 66,685 patients were included. The serious adverse events (SAEs) of AF/AFL occurrence were significantly lower in the SGLT2i group than the placebo group (0.96% vs. 1.19%; RR 0.83; 95% CI 0.71-0.96; P = 0.01; I2 25.5%). Similarly, the SAEs of AF occurrence was significantly lower in the SGLT2i group (0.82% vs. 1.06%; RR 0.81; 95% CI 0.69-0.95; P = 0.01; I2 10.2%). The subgroup analysis showed that the reduction in AF/AFL was significant only for dapagliflozin (1.02% vs. 1.49%; RR 0.73; 95% CI 0.59-0.89; P = 0.002; I2 0%), but not for canagliflozin (1.00% vs 1.08%; RR 0.83; 95% CI 0.62-1.12; P = 0.23; I2 0%), empagliflozin (0.88% vs 0.70%; RR 1.20; 95% CI 0.76-1.90; P = 0.43; I2 0%), ertugliflozin (1.01% vs 0.96%; RR 1.08; 95% CI 0.66-1.75; P = 0.76; I2 0%), and sotagliflozin (0.16% vs 0.10%; RR 1.09; 95% CI 0.13-8.86; P = 0.93; I2 0%). Conclusions: SGLT2i use is associated with a 19.33% lower SAEs of AF/AFL compared with the placebo. Dapagliflozin users had the lowest SAEs of AF/AFL incidence. Further studies are needed to determine whether canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin similarly exert protective effects against AF/AFL development.

Territory-wide cohort study of Brugada syndrome in Hong Kong: predictors of long-term outcomes using random survival forests and non-negative matrix factorisation.

OBJECTIVES: Brugada syndrome (BrS) is an ion channelopathy that predisposes affected patients to spontaneous ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death. The aim of this study is to examine the predictive factors of spontaneous VT/VF. METHODS: This was a territory-wide retrospective cohort study of patients diagnosed with BrS between 1997 and 2019. The primary outcome was spontaneous VT/VF. Cox regression was used to identify significant risk predictors. Non-linear interactions between variables (latent patterns) were extracted using non-negative matrix factorisation (NMF) and used as inputs into the random survival forest (RSF) model. RESULTS: This study included 516 consecutive BrS patients (mean age of initial presentation=50±16 years, male=92%) with a median follow-up of 86 (IQR: 45-118) months. The cohort was divided into subgroups based on initial disease manifestation: asymptomatic (n=314), syncope (n=159) or VT/VF (n=41). Annualised event rates per person-year were 1.70%, 0.05% and 0.01% for the VT/VF, syncope and asymptomatic subgroups, respectively. Multivariate Cox regression analysis revealed initial presentation of VT/VF (HR=24.0, 95% CI=1.21 to 479, p=0.037) and SD of P-wave duration (HR=1.07, 95% CI=1.00 to 1.13, p=0.044) were significant predictors. The NMF-RSF showed the best predictive performance compared with RSF and Cox regression models (precision: 0.87 vs 0.83 vs. 0.76, recall: 0.89 vs. 0.85 vs 0.73, F1-score: 0.88 vs 0.84 vs 0.74). CONCLUSIONS: Clinical history, electrocardiographic markers and investigation results provide important information for risk stratification. Machine learning techniques using NMF and RSF significantly improves overall risk stratification performance.

Arrhythmogenic Mechanisms in Hypokalaemia: Insights From Pre-clinical Models.

Potassium is the predominant intracellular cation, with its extracellular concentrations maintained between 3. 5 and 5 mM. Among the different potassium disorders, hypokalaemia is a common clinical condition that increases the risk of life-threatening ventricular arrhythmias. This review aims to consolidate pre-clinical findings on the electrophysiological mechanisms underlying hypokalaemia-induced arrhythmogenicity. Both triggers and substrates are required for the induction and maintenance of ventricular arrhythmias. Triggered activity can arise from either early afterdepolarizations (EADs) or delayed afterdepolarizations (DADs). Action potential duration (APD) prolongation can predispose to EADs, whereas intracellular Ca2+ overload can cause both EADs and DADs. Substrates on the other hand can either be static or dynamic. Static substrates include action potential triangulation, non-uniform APD prolongation, abnormal transmural repolarization gradients, reduced conduction velocity (CV), shortened effective refractory period (ERP), reduced excitation wavelength (CV × ERP) and increased critical intervals for re-excitation (APD-ERP). In contrast, dynamic substrates comprise increased amplitude of APD alternans, steeper APD restitution gradients, transient reversal of transmural repolarization gradients and impaired depolarization-repolarization coupling. The following review article will summarize the molecular mechanisms that generate these electrophysiological abnormalities and subsequent arrhythmogenesis.

Soluble suppression of tumorigenicity 2 (sST2) for predicting disease severity or mortality outcomes in cardiovascular diseases: A systematic review and meta-analysis.

OBJECTIVES: Soluble suppression of tumorigenicity 2 (sST2) is a member of the interleukin-1 receptor family. It is raised in various cardiovascular diseases, but its value in predicting disease severity or mortality outcomes has been controversial. Therefore, we conducted a systematic review and meta-analysis to determine whether sST2 levels differed between survivors and non-survivors of patients with cardiovascular diseases, and whether elevated sST2 levels correlated with adverse outcomes. METHODS: PubMed and Embase were searched until 23rd June 2021 for studies that evaluated the relationship between sST2 levels and cardiovascular disease severity or mortality. RESULTS: A total of 707 entries were retrieved from both databases, of which 14 studies were included in the final meta-analysis. In acute heart failure, sST2 levels did not differ between survivors and non-survivors (mean difference [MD]: 24.2 ± 13.0 ng/ml; P = 0.06; I 2: 95%). Elevated sST2 levels tend to be associated with increased mortality risk (hazard ratio [HR]: 1.12, 95 %CI: 0.99-1.27, P = 0.07; I 2: 88%). In chronic heart failure, sST2 levels were higher in non-survivors than in survivors (MD: 0.19 ± 0.04 ng/ml; P = 0.001; I 2: 0%) and elevated levels were associated with increased mortality risk (HR: 1.64, 95% CI: 1.27-2.12, P < 0.001; I 2: 82%). sST2 levels were significantly higher in severe disease compared to less severe disease (MD: 1.56 ± 0.46 ng/ml; P = 0.001; I 2: 98%). Finally, in stable coronary artery disease, sST2 levels were higher in non-survivors than survivors (MD: 3.0 ± 1.1 ng/ml; P = 0.005; I 2: 80%) and elevated levels were significantly associated with increased mortality risk (HR: 1.32, 95% CI: 1.04-1.68, P < 0.05; I 2: 57%). CONCLUSIONS: sST2 significantly predicts disease severity and mortality in cardiovascular disease and is a good predictor of mortality in patients with stable coronary artery disease and chronic heart failure.

Restitution metrics in Brugada syndrome: a systematic review and meta-analysis.

BACKGROUND: Brugada syndrome (BrS) is an ion channelopathy that predisposes affected subjects to ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death. Restitution analysis has been examined in BrS patients but not all studies have reported significant differences between BrS patients and controls. Therefore, we conducted a systematic review and meta-analysis to investigate the different restitution indices used in BrS. METHODS: PubMed and Embase were searched until April 7, 2019, identifying 20 and 27 studies. RESULTS: A total of ten studies involving 178 BrS (mean age 38 years old, 63% male) and 102 controls (mean age 31 years old, 42% male) were included in this systematic review. Pacing was carried out at the right ventricular outflow tract (RVOT)/right ventricular apex (RPA) (n = 4), RPA (n = 4), or right atrium (RA) (n = 1). Basic cycle lengths of 400 (n = 4), 500 (n = 2), 600 (n = 6) and 750 ms (n = 1) were used. Recording methods include electrograms (n = 4), monophasic action potentials (n = 5), and electrocardiograms (n = 1). Signals were obtained from the RVOT (n = 8), RVA (n = 3), RA (n = 1), or the body surface (n = 1). The maximum restitution slope for endocardial repolarization at the RVOT was 0.87 for BrS patients (n = 5; 95% confidence interval [CI] 0.68-1.07) compared with 0.74 in control subjects (n = 4; 95% CI 0.42-1.06), with a significant mean difference of 0.40 (n = 4; 95% CI 0.11-0.69; P = 0.007). CONCLUSIONS: Steeper endocardial repolarization restitution slopes are found in BrS patients compared with controls at baseline. Restitution analysis can provide important information for risk stratification in BrS.

Outcomes in Brugada Syndrome Patients With Implantable Cardioverter-Defibrillators: Insights From the SGLT2 Registry.

BACKGROUND AND OBJECTIVES: Brugada syndrome (BrS) is a cardiac ion channelopathy with characteristic electrocardiographic patterns, predisposing affected individuals to sudden cardiac death (SCD). Implantable cardioverter-defibrillator (ICD) is used for primary or secondary prevention in BrS, but its use remains controversial amongst low-risk asymptomatic patients. The present study aims to examine indicators for ICD implantation amongst BrS patients with different disease manifestations. METHODS: This study included BrS patients who received ICDs between 1997 and 2018. The cohort was divided into three categories based on presentations before ICD implantation: asymptomatic, syncope, ventricular tachycardia/ventricular fibrillation (VT/VF). Univariate and multivariate Cox-regression analysis were performed to identify independent predictors of appropriate and inappropriate shock delivery. RESULTS: A total of 136 consecutive patients were included with a median follow-up of 95 (IQR: 80) months. Appropriate shocks were delivered in 34 patients (25.0%) whereas inappropriate shocks were delivered in 24 patients (17.6%). Complications occurred in 30 patients (22.1%). Type 1 Brugada pattern were found to be an independent predictor of appropriate shock delivery, whilst the presence of other arrhythmia was predictive for both appropriate and inappropriate ICD shock delivery under multivariate Cox regression analysis. CONCLUSION: ICD therapy is effective for primary and secondary prevention of SCD in BrS. Whilst appropriate shocks occur more frequently in BrS patients presenting with VT/VF, they also occur in asymptomatic patients. Further research in risk stratification can improve patient prognosis while avoid unnecessary ICD implantation.

P-Wave Area Predicts New Onset Atrial Fibrillation in Mitral Stenosis: A Machine Learning Approach.

Introduction: Mitral stenosis is associated with an atrial cardiomyopathic process, leading to abnormal atrial electrophysiology, manifesting as prolonged P-wave duration (PWD), larger P-wave area, increased P-wave dispersion (PWDmax-PWDmin), and/or higher P-wave terminal force on lead V1 (PTFV1) on the electrocardiogram. Methods: This was a single-center retrospective study of Chinese patients, diagnosed with mitral stenosis in sinus rhythm at baseline, between November 2009 and October 2016. Automated ECG measurements from raw data were determined. The primary outcome was incident atrial fibrillation (AF). Results: A total 59 mitral stenosis patients were included (age 59 [54-65] years, 13 (22%) males). New onset AF was observed in 27 patients. Age (odds ratio [OR]: 1.08 [1.01-1.16], P = 0.017), systolic blood pressure (OR: 1.03 [1.00-1.07]; P = 0.046), mean P-wave area in V3 (odds ratio: 3.97 [1.32-11.96], P = 0.014) were significant predictors of incident AF. On multivariate analysis, age (OR: 1.08 [1.00-1.16], P = 0.037) and P-wave area in V3 (OR: 3.64 [1.10-12.00], P = 0.034) remained significant predictors of AF. Receiver-operating characteristic (ROC) analysis showed that the optimum cut-off for P-wave area in V3 was 1.45 Ashman units (area under the curve: 0.65) for classification of new onset AF. A decision tree learning model with individual and non-linear interaction variables with age achieved the best performance for outcome prediction (accuracy = 0.84, precision = 0.84, recall = 0.83, F-measure = 0.84). Conclusion: Atrial electrophysiological alterations in mitral stenosis can detected on the electrocardiogram. Age, systolic blood pressure, and P-wave area in V3 predicted new onset AF. A decision tree learning model significantly improved outcome prediction.

Correction to: Restitution metrics in Brugada syndrome: a systematic review and meta-analysis.

The original version of this article unfortunately has a typo error. The name of the author "Kamalan Jeeveratnam" should be presented as "Kamalan Jeevaratnam" as shown above.

Brugada syndrome: A comprehensive review of pathophysiological mechanisms and risk stratification strategies.

Brugada syndrome (BrS) is an inherited ion channel channelopathy predisposing to ventricular arrhythmias and sudden cardiac death. Originally believed to be predominantly associated with mutations in SCN5A encoding for the cardiac sodium channel, mutations of 18 genes other than SCN5A have been implicated in the pathogenesis of BrS to date. Diagnosis is based on the presence of a spontaneous or drug-induced coved-type ST segment elevation. The predominant electrophysiological mechanism underlying BrS remains disputed, commonly revolving around the three main hypotheses based on abnormal repolarization, depolarization or current-load match. Evidence from computational modelling, pre-clinical and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening ventricular arrhythmic events. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers. Current treatment options include pharmacological therapy to reduce the occurrence of arrhythmic events or to abort these episodes, and interventions such as implantable cardioverter-defibrillator insertion or radiofrequency ablation of abnormal arrhythmic substrate.