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Atrial fibrosis is a hallmark of atrial cardiomyopathy and plays a pivotal role in the pathogenesis of atrial fibrillation (AF), contributing to its onset and progression. The mechanisms underlying atrial fibrosis are multifaceted, involving stretch-induced fibroblast activation, oxidative stress, inflammation, and coagulation pathways. Variations in fibrosis types—reactive and replacement fibrosis—are influenced by patient-specific factors such as age, sex, and comorbidities, complicating therapeutic approaches. The heterogeneity of fibrosis leads to distinct electrophysiological abnormalities that promote AF via reentrant activity and enhanced automaticity mechanisms. Despite advancements in imaging, such as late gadolinium enhancement CMR and electroanatomical mapping, challenges in accurately quantifying fibrosis persist. Emerging therapeutic strategies include antifibrotic agents targeting the renin–angiotensin–aldosterone system, novel pathways like TGF-β signaling, and cardio-metabolic drugs like SGLT2 inhibitors and GLP-1 receptor agonists. Innovative interventions, including microRNA modulation and lipid nanoparticle-based therapies, show promise but require validation. Knowledge gaps remain in correlating clinical outcomes with fibrosis patterns and optimizing diagnostic tools. Future research should focus on precise phenotyping, integrating advanced imaging with molecular biomarkers, and conducting robust trials to evaluate antifibrotic therapies' efficacy in reducing AF burden and related complications. [ABSTRACT FROM AUTHOR]

This study aimed to explore the impact of a combination of hyperuricemia (HUA) and excessive high-sensitivity C-reactive protein (hs-CRP) levels on the likelihood of developing cardiac conduction block (CCB). Additionally, it sought to assess whether the influence of uric acid (UA) on CCB is mediated by hs-CRP. Methods: A prospective study was executed utilizing data from the Kailuan cohort, including 81,896 individuals initially free from CCB. The participants were categorized into four groups depending on the existence of HUA and low-grade inflammation (hs-CRP> 3 mg/L). Cox regression analysis was employed to ascertain hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CCB. A mediation analysis was performed to determine if hs-CRP functioned as a mediator in the connection between UA levels and the incidence of CCB. Results: During a median observation period of 11.8 years, we identified 3160 cases of newly occurring CCB. Compared with the low UA/low CRP group, the combination of HUA and low-grade inflammation elevated the CCB risks (HR:1.56, 95% CI:1.22– 1.99), atrioventricular block (AVB) (HR:1.88, 95% CI:1.27– 2.77), and right bundle branch block (HR:1.47, 95% CI:1.02– 2.12), respectively. Mediation analysis revealed that in the HUA group, compared with the non-HUA group, the risk of CCB elevated by 14.0%, with 10.3% of the increase mediated through hs-CRP. Conclusion: HUA combined with elevated hs-CRP increased the risk of CCB, especially AVB. The connection between UA and the CCB risk was partly mediated by hs-CRP. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) and atrial flutter (AFL) are associated with adverse outcomes in patients with heart failure and reduced ejection fraction (HFrEF). We investigated the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on the incidence of AF and/or AFL in HFrEF patients. PubMed and ClinicalTrials.gov were systematically searched until March 2022 for randomized controlled trials (RCTs) that enrolled patients with HFrEF. A total of six RCTs with 9467 patients were included (N = 4731 in the SGLT2i arms; N = 4736 in the placebo arms). Compared to placebo, SGLT2i treatment was associated with a significant reduction in the risk of AF [relative risk (RR) 0.62, 95% confidence interval CI 0.44–0.86; P = 0.005] and AF/AFL (RR 0.64, 95% CI 0.47–0.87; P = 0.004). Subgroup analysis showed that empagliflozin use resulted in a significant reduction in the risk of AF (RR 0.55, 95% CI 0.34–0.89; P = 0.01) and AF/AFL (RR 0.50, 95% CI 0.32–0.77; P = 0.002). By contrast, dapagliflozin use was not associated with a significant reduction in the risk of AF (RR 0.69, 95% CI 0.43–1.11; P = 0.12) or AF/AFL (RR 0.82, 95% CI 0.53–1.27; P = 0.38). Additionally, a "shorter" duration (< 1.5 years) of treatment with SGLT2i remained associated with a reduction in the risk of AF (< 1.5 years; RR 0.58, 95% CI 0.36–0.91; P = 0.02) and AF/AFL (< 1.5 years; RR 0.52, 95% CI 0.34–0.80; P = 0.003). In conclusion, SGLT2i therapy was associated with a significant reduction in the risk of AF and AF/AFL in patients with HFrEF. These results reinforce the value of using SGLT2i in this setting. [ABSTRACT FROM AUTHOR]

Despite the strict indications for cardiac resynchronization therapy (CRT) implantation, a significant proportion of patients will fail to adequately respond to the treatment. This systematic review aims to present the existing evidence about the role of cardiac magnetic resonance (CMR) in identifying patients who are likely to respond better to the CRT. A systematic search in the MedLine database and Cochrane Library from their inception to August 2021 was performed, without any limitations, by two independent investigators. We considered eligible observational studies or randomized clinical trials (RCTs) that enrolled patients > 18 years old with heart failure (HF) of ischaemic or non-ischaemic aetiology and provided data about the association of baseline CMR variables with clinical or echocardiographic response to CRT for at least 3 months. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA Statement). Following our search strategy, 47 studies were finally included in our review. CMR appears to have an additive role in identifying the subgroup of patients who will respond better to CRT. Specifically, the presence and the extent of myocardial scar were associated with increased non-response rates, while those with no scar respond better. Furthermore, existing data show that scar location can be associated with CRT response rates. CMR-derived markers of mechanical desynchrony can also be used as predictors of CRT response. CMR data can be used to optimize the position of the left ventricular lead during the CRT implantation procedure. Specifically, positioning the left ventricular lead in a branch of the coronary sinus that feeds an area with transmural scar was associated with poorer response to CRT. CMR can be used as a non-invasive optimization tool to identify patients who are more likely to achieve better clinical and echocardiographic response following CRT implantation. [ABSTRACT FROM AUTHOR]

Background: Electrocardiographic non-invasive risk factors (NIRFs) have an important role in the arrhythmic risk stratification of post-myocardial infarction (post-MI) patients with preserved or mildly reduced left ventricular ejection fraction (LVEF). However, their specific relation to left ventricular systolic function remains unclear. We aimed to evaluate the association between NIRFs and LVEF in the patients included in the PRESERVE-EF trial.Methods: We studied 575 post-MI ischemia-free patients with LVEF≥40% (mean age: 57.0 ± 10.4 years, 86.2% men). The following NIRFs were evaluated: premature ventricular complexes, non-sustained ventricular tachycardia (NSVT), late potentials (LPs), prolonged QTc, increased T-wave alternans, reduced heart rate variability, and abnormal deceleration capacity with abnormal turbulence.Results: There was a statistically significant relationship between LPs (Chi-squared = 4.975; p < .05), nsVT (Chi-squared = 5.749, p < .05), PVCs (r= -.136; p < .01), and the LVEF. The multivariate linear regression analysis showed that LPs (p = .001) and NSVT (p < .001) were significant predictors of the LVEF. The results of the multivariate logistic regression analysis indicated that LPs (OR: 1.76; 95% CI: 1.02-3.05; p = .004) and NSVT (OR: 2.44; 95% CI: 1.18-5.04; p = .001) were independent predictors of the mildly reduced LVEF: 40%-49% versus the preserved LVEF: ≥50%.Conclusion: Late potentials and NSVT are independently related to reduced LVEF while they are independent predictors of mildly reduced LVEF versus the preserved LVEF. These findings may have important implications for the arrhythmic risk stratification of post-MI patients with mildly reduced or preserved LVEF. [ABSTRACT FROM AUTHOR]

Brugada syndrome (BrS) is a complex arrhythmogenic disease displaying electrical and micro-structural abnormalities mainly located at the epicardium of the right ventricular outflow tract (RVOT). It is well-known that fibrosis, fatty infiltration, inflammation and reduced gap junction expression have been demonstrated at the epicardial anterior aspect of the RVOT providing the arrhythmogenic substrate for ventricular arrhythmic events in BrS. A number of models have been proposed for the risk stratification of patients with BrS. Endocardial unipolar electroanatomical mapping is an emerging tool that has been reintroduced to identify and quantify epicardial electrical abnormalities. Interestingly, current findings correlate the presence of large-sized endocardial unipolar electroanatomical abnormalities with either ventricular fibrillation inducibility during programmed ventricular stimulation or symptom status. This review aims to present existing data about the role of endocardial unipolar electroanatomical mapping for the identification of RVOT epicardial abnormalities as well as its potential clinical implications in risk stratification of BrS. [ABSTRACT FROM AUTHOR]

Background: In the PRESERVE‐EF study, a two‐step sudden cardiac death (SCD) risk stratification approach to detect post‐myocardial infarction (MI) patients with left ventricle ejection fraction (LVEF) ≥40% at risk for major arrhythmic events (MAEs) was used. Seven noninvasive risk factors (NIRFs) were extracted from a 24‐h ambulatory electrocardiography (AECG) and a 45‐min resting recording. Patients with at least one NIRF present were referred for invasive programmed ventricular stimulation (PVS) and inducible patients received an Implantable Cardioverter ‐ Defibrillator (ICD). Methods: In the present study, we evaluated the performance of the NIRFs, as they were described in the PRESERVE‐EF study protocol, in predicting a positive PVS. In the PRESERVE‐EF study, 152 out of 575 patients underwent PVS and 41 of them were inducible. For the present analysis, data from these 152 patients were analyzed. Results: Among the NIRFs examined, the presence of signal averaged ECG‐late potentials (SAECG‐LPs) ≥ 2/3 and non‐sustained ventricular tachycardia (NSVT) ≥1 eposode/24 h cutoff points were important predictors of a positive PVS study, demonstrating in the logistic regression analysis odds ratios 2.285 (p =.027) and 2.867 (p =.006), respectively. A simple risk score based on the above cutoff points in combination with LVEF < 50% presented high sensitivity but low specificity for a positive PVS. Conclusion: Cutoff points of NSVT ≥ 1 episode/24 h and SAECG‐LPs ≥ 2/3 in combination with a LVEF < 50% were important predictors of inducibility. However, the final decision for an ICD implantation should be based on a positive PVS, which is irreplaceable in risk stratification. [ABSTRACT FROM AUTHOR]

Aims: Sudden cardiac death (SCD) and ventricular arrhythmias (VAs) are important causes of mortality in patients with type 2 diabetes mellitus (T2DM), heart failure (HF), or chronic kidney disease (CKD). We evaluated the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on SCD and VAs in these patients.Methods and Results: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that enrolled patients with T2DM and/or HF and/or CKD comparing SGLT2i and placebo or active control. PubMed and ClinicalTrials.gov were systematically searched until November 2020. A total of 19 RCTs with 55 ,590 participants were included. Sudden cardiac death events were reported in 9 RCTs (48 patients receiving SGLT2i and 57 placebo subjects). There was no significant association between SGLT2i therapy and SCD [risk ratio (RR) 0.74, 95% confidence interval (CI) 0.50-1.08; P = 0.12]. Ventricular arrhythmias were reported in 17 RCTs (126 patients receiving SGLT2i and 134 controls). SGLT2i therapy was not associated with a lower risk of VAs (RR 0.84, 95% CI 0.66-1.06; P = 0.14). Besides the subgroup of low-dosage SGLT2i therapy that demonstrated decreased VAs compared to control (RR 0.45, 95% CI 0.25-0.82; P = 0.009), or to placebo (RR 0.46, 95% CI 0.25-0.85; P = 0.01), further subgroup analysis did not demonstrate any significant differences.Conclusion: SGLT2i therapy was not associated with an overall lower risk of SCD or VAs in patients with T2DM and/or HF and/or CKD. However, further research is needed since the number of SCD and VA events were relatively few leading to wide confidence intervals, and the point estimates suggested potential benefits. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a leading cause of morbidity and mortality worldwide. Assessment of cardiovascular (CV) and all-cause mortality in CKD patients is of particular importance. CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes, prior stroke, vascular disease, age 65–74 years, and sex) score was originally formulated to predict the annual thromboembolic risk in patients with nonvalvular atrial fibrillation (AF). The calculation of R2CHADS2 and R2CHA2DS2VASc scores awarded an additional 2 points for CrCl < 60 mL/min and GFR < 60 mL/min/1.73 m2. Recent studies have investigated whether CHA2DS2-VASc and R2CHADS ± VASC scores could be used to predict CV or all-cause mortality in patients with CKD. CHA2DS2-VASc score was proven to be a significant predictor of CV and all-cause mortality in CKD patients, and a higher CHA2DS2-VASc score was associated with increased mortality. These findings are quite promising, and they may help physicians to identify high-risk groups in this population. [ABSTRACT FROM AUTHOR]

Dyskalemia (hypo- and hyperkalemia) is a common clinical encounter in patients with heart failure (HF), linked to underlying pathophysiologic alterations, pharmacological treatments, and concomitant comorbidities. Both hypo- and hyperkalemia have been associated with a poor outcome in HF. However, it is not known if this association is causal. In order to investigate this relation, we implemented the Bradford Hill criteria for causation examining the available literature. Of note, hypokalemia and low-normal potassium levels (serum potassium < 4.0 mmol/L) appear to be associated with adverse clinical outcomes in HF in a cause-and-effect manner. Conversely, a cause-and-effect relationship between hyperkalemia (serum potassium > 5.0 mmol/L) and adverse clinical outcomes in HF appears unlikely. We also examined the benefits of renin-angiotensin-aldosterone system inhibitors (RAASi) therapy uptitration in patients with HF and reduced ejection fraction. In fact, hyperkalemia often limits RAASi use, thereby negating or mitigating their clinical benefits. Finally, serum potassium levels in HF should be maintained within the range of 4.0–5.0 mmol/L, and although the correction of hyperkalemia does not appear to improve clinical outcomes per se, it may enable the optimal titration of RAASi, offering indirect clinical benefit. [ABSTRACT FROM AUTHOR]

Prolonged QRS duration, which reflects a higher degree of mechanical dysynchrony, is a predictor of response to CRT. However, the association of QRS narrowing after biventricular pacing with CRT response rates is not clear. Our aim was to conduct a systematic review and meta-analysis on the association between QRS narrowing after cardiac resynchronization therapy (CRT) and clinical and echocardiographic response to CRT in patients with heart failure. Two independent investigators searched MedLine and EMBASE databases through July 2018 without any limitations. Studies providing estimates (continuous data) on the association of QRS shortening with either clinical (defined as New York Heart Association (NYHA) reduction ≥ 1) or echocardiographic (defined as left ventricular end-systolic volume (LVESV) reduction ≥ 15%) response to CRT were finally included in the quantitative synthesis. We included 32 studies (14 studies (1274 patients mean age 64 years old, males 79.3%) using clinical CRT response and 18 studies (1270 patients, mean age 64 years old, males 69.1%) using echocardiographic CRT response). A significant association between QRS narrowing and shorter attained QRS duration with clinical and echocardiographic CRT response was observed. The observed association was independent of the timing of QRS width measurement after CRT implantation. Acute and late improvement of electrical dysynchrony as depicted by QRS narrowing following biventricular pacing is associated with clinical and echocardiographic response to CRT. However, large prospective studies are needed to further examine our findings. [ABSTRACT FROM AUTHOR]

Purpose of Review: Excessive supraventricular ectopic activity (ESVEA), in the form of frequent premature atrial contractions (PACs) and runs of PACs, is commonly observed in clinical practice and is frequently considered to be benign. Yet, recent studies have demonstrated a link between ESVEA and adverse cardiovascular outcomes. The aim of this meta-analysis was to examine the association between ESVEA and the risk of atrial fibrillation (AF), stroke, and mortality. Recent Findings: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library up to December 2017 to identify studies assessing adverse cardiovascular outcomes in patients with ESVEA, recorded on ambulatory electrocardiography. ESVEA was defined as a burden of PACs > 30 PACs/h or any runs of ≥20 PACs. The risk estimates for EVSEA and each clinical endpoint were pooled and analyzed separately. Results: Five studies comprising 7545 participants were included in this meta-analysis. The pooled analysis showed that ESVEA doubled the risk of AF (HR 2.19, 95% CI 1.70–2.82). ESVEA was also associated with a higher incidence of stroke (HR 2.23, 95% CI 1.24–4.02). Finally, ESVEA was associated with higher all-cause mortality (HR 1.61, 95% CI 1.25–2.07). Summary: Our meta-analysis found that ESVEA is closely associated with AF, stroke, and all-cause mortality. Further studies are required to examine the implication of therapeutic strategies in patients with ESVEA, in order to prevent potential subsequent adverse cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is considered a significant challenge in cardiovascular medicine related to significant morbidity and mortality. Obstructive sleep apnea (OSA) is associated with stroke and constitutes an important risk factor for AF. However, it is still ambiguous whether OSA is independently related to stroke or systemic embolism in AF patients, and whether or not OSA should be included in CHA2DS2-VASc score. In a recent study, the presence of OSA in patients with AF was associated with higher rates of adverse events, namely stroke and systemic embolism. Patients with OSA have higher CHA2DS2-VASc scores and mean CHA2DS2-VASc scores that increase with OSA severity. The addition of OSA to CHA2DS2-VASc resulted in improved discrimination, but this improvement was modest and clinically non-significant. However, cardiovascular risk factors that accompany OSA and not OSA per se might be responsible for the increased thromboembolic risk in these patients. It is noteworthy that patients with OSA with CHA2DS2-VASc <2 had a higher incidence of stroke compared to those without. Unfortunately, the event rates for stroke in these patients were too low to reach statistically validated conclusions. Therefore, it seems reasonable to suggest that in borderline stroke risk patients (CHA2DS2-VASc <2), the presence of OSA should be taken into account in the treatment decision. More studies are needed to elucidate whether or not OSA should be incorporated in CHA2DS2-VASc score. [ABSTRACT FROM AUTHOR]

Aims: Risk stratification in Brugada syndrome (BrS) still represents an unsettled issue. In this multicentre study, we aimed to evaluate the clinical characteristics and the long-term clinical course of patients with BrS.Methods and Results: A total of 111 consecutive patients (86 males; aged 45.3 ± 13.3 years) diagnosed with BrS were included and followed-up in a prospective fashion. Thirty-seven patients (33.3%) were symptomatic at enrolment (arrhythmic syncope). An electrophysiological study (EPS) was performed in 59 patients (53.2%), and ventricular arrhythmias were induced in 32 (54.2%). A cardioverter defibrillator was implanted in 34 cases (30.6%). During a mean follow-up period of 4.6 ± 3.5 years, appropriate device therapies occurred in seven patients. Event-free survival analysis (log-rank test) showed that spontaneous type-1 electrocardiogram pattern (P = 0.008), symptoms at presentation (syncope) (P = 0.012), family history of sudden cardiac death (P < 0.001), positive EPS (P = 0.024), fragmented QRS (P = 0.004), and QRS duration in lead V2 > 113 ms (P < 0.001) are predictors of future arrhythmic events. Event rates were 0%, 4%, and 60% among patients with 0-1 risk factor, 2-3 risk factors, and 4-5 risk factors, respectively (P < 0.001). Current multiparametric score models exhibit an excellent negative predictive value and perform well in risk stratification of BrS patients.Conclusions: Multiparametric models including common risk factors appear to provide better risk stratification of BrS patients than single factors alone. [ABSTRACT FROM AUTHOR]

Aims Sudden cardiac death (SCD) annual incidence is 0.6–1% in post-myocardial infarction (MI) patients with left ventricular ejection fraction (LVEF)≥40%. No recommendations for implantable cardioverter-defibrillator (ICD) use exist in this population. Methods and results We introduced a combined non-invasive/invasive risk stratification approach in post-MI ischaemia-free patients, with LVEF ≥ 40%, in a multicentre, prospective, observational cohort study. Patients with at least one positive electrocardiographic non-invasive risk factor (NIRF): premature ventricular complexes, non-sustained ventricular tachycardia, late potentials, prolonged QTc, increased T-wave alternans, reduced heart rate variability, abnormal deceleration capacity with abnormal turbulence, were referred for programmed ventricular stimulation (PVS), with ICDs offered to those inducible. The primary endpoint was the occurrence of a major arrhythmic event (MAE), namely sustained ventricular tachycardia/fibrillation, appropriate ICD activation or SCD. We screened and included 575 consecutive patients (mean age 57 years, LVEF 50.8%). Of them, 204 (35.5%) had at least one positive NIRF. Forty-one of 152 patients undergoing PVS (27–7.1% of total sample) were inducible. Thirty-seven (90.2%) of them received an ICD. Mean follow-up was 32 months and no SCDs were observed, while 9 ICDs (1.57% of total screened population) were appropriately activated. None patient without NIRFs or with NIRFs but negative PVS met the primary endpoint. The algorithm yielded the following: sensitivity 100%, specificity 93.8%, positive predictive value 22%, and negative predictive value 100%. Conclusion The two-step approach of the PRESERVE EF study detects a subpopulation of post-MI patients with preserved LVEF at risk for MAEs that can be effectively addressed with an ICD. Clinicaltrials.gov identifier NCT02124018 Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

The present study reports on a family with two members affected by Danon disease but having different phenotypes. The clinical manifestations of Danon disease include cardiomyopathy, skeletal myopathy and different degrees of intellectual disability that varies greatly among patients. The present case study reports on two siblings, an older sister and a younger brother, with Danon disease from an affected pedigree, presenting with distinctly different phenotypes. The sister was diagnosed with dilated cardiomyopathy at the age of 26 years with an unfavorable outcome, while her younger brother presented with hypertrophic cardiomyopathy in a relatively stable state. The two probands shared the same mutation, c.974delTinsAA in exon 8, in the lysosomal-associated membrane protein-2 gene. Of note, the two patients had a pre-excitation pattern in the electrocardiogram on initial presentation and later developed atrial fibrillation (AF), which markedly aggravated heart failure. To the best of our knowledge, AF has not been widely reported in patients with Danon disease. The development of AF may have a prognostic value under these circumstances. [ABSTRACT FROM AUTHOR]

Aims. Previous studies have demonstrated epidemiological evidence for an association between cancer and the development of new-onset atrial fibrillation (AF). However, these results have been conflicting. This systematic review and meta-analysis was conducted to examine the relationship between cancer and the risk of developing atrial fibrillation. Methods. PubMed and Web of Science were searched for publications examining the association between cancer and atrial fibrillation risk published until June 2017. Adjusted odds ratios (ORs) or hazard ratios (HRs) and 95% CI were extracted and pooled. Results. A total of five studies involving 5,889,234 subjects were included in this meta-analysis. Solid cancer patients are at higher risk developing atrial fibrillation compared to noncancer patients (OR 1.47, 95% CI 1.31 to 1.66, p<0.00001; I2 = 67%, p=0.02). The risk of atrial fibrillation was highest within 90 days of cancer diagnosis (OR 7.62, 95% CI 3.08 to 18.88, p<0.00001) and this risk diminished with time. Conclusions. The risk of AF was highest within 90 days of cancer diagnosis. We should take into account the increased risk of atrial fibrillation development and, after this, study the embolic risk and potential indication of oral anticoagulation. [ABSTRACT FROM AUTHOR]

A 66‐year‐old man, implanted Abbott dual‐chamber pacemaker, was admitted to our hospital due to recurrent palpitation. ECG was recorded on admission, which created a diagnostic confusion: What accounts for the appearance of the VP in the setting of a stable intrinsic atrioventricular (AV) conduction? In this case, we will focus on the logical reasoning in the analysis of Pacing ECG. [ABSTRACT FROM AUTHOR]

Background. Use of amiodarone (AMIO) in atrial fibrillation (AF) has significant side effects over prolonged periods. Wenxin Keli (WXKL), a Chinese herb extract, has been shown to be effective in atrial-selective inhibiting peak INa and hence beneficial in treating atrial arrhythmias, including atrial fibrillation. The aim of this randomized controlled trial was to evaluate potential effects of AMIO plus WXKL on conversion rate and time in patients with recent-onset AF. Methods. A total of 41 patients (71 ± 12 years, 44% male) with recent-onset (<48 h) AF eligible for conversion were randomized to receive either intravenous amiodarone (loading dose 5 mg/kg in 1 hour followed by 50 mg/h; n=21) or amiodarone with same dosage plus oral WXKL 18 g thrice daily (n=20) for 24 hours. Results. Conversion rate at 24 hours was of no difference between the two groups (75.0% vs. 81.0%, P=0.72); however, conversion time was markedly shorter in the AMIO + WXKL group compared to the AMIO group (291 ± 235 minutes vs. 725 ± 475 minutes, P=0.003). There were no serious adverse events during the study. Conclusion. Administration of amiodarone plus WXKL for recent-onset AF conversion was safe and effective, with faster sinus rhythm restoration compared with amiodarone alone. [ABSTRACT FROM AUTHOR]

Atrial remodelling involves electrophysiological and structural abnormalities that promote the development and perpetuation of atrial fibrillation. Experimental and clinical data indicate that oxidative stress is implicated in the pathophysiology of atrial remodelling. The mechanistic links between atrial remodelling and oxidative stress are complex with several underlying diseases and conditions may affect these pathways. Therefore, the development of antioxidant interventions in this setting remains difficult. Besides classical antioxidant compounds, several agents with pleiotropic effects, including anti-inflammatory and antioxidant, have been tested in experimental and clinical settings with variable results. Strategies applying conventional antioxidants in specific situations such as postoperative atrial fibrillation show beneficial effects, especially the two-step regimen of antioxidants combination. Of note, there are limited data on the development of strategies that target specific sources of reactive oxygen species implicated in atrial remodelling. Lifestyle, diet, and risk factors modification is a complementary promising approach. This updated review provides a concise and critical overview of all available data regarding oxidative stress and its modulation in atrial fibrillation. Future directions on this exciting field are also discussed. [ABSTRACT FROM AUTHOR]

Background: The early and correct diagnosis of cardiac implantable electronic device (CIED) infections is critical given that early aggressive treatment with complete removal of the system along with antimicrobial therapy dramatically improves outcomes. Pocket infection manifested by local signs of inflammation is the most common form of CIED infections. Conditions mimicking pocket infection have been described in the literature. These include various types of malignancy and rarely allergic reactions/ contact dermatitis to pacemaker compounds. We aimed to describe skin lesions and disorders over the pocket area that mimic CIED infection.Methods: We present a series of five cases with skin lesions that mimic pocket infection. We document these cases with corresponding photographs. Most of them have not been described in this setting.Results: We report the following cases of conditions that proved not to be CIED infection: One case of superficial cellulitis, one case of herpes zoster over the pocket area, one case of spontaneous bruising over the pocket along time after implantation in a patient taking oral anticoagulation, and two cases of contact dermatitis due to prolonged postoperative application of povidoneiodine. All cases had favorable outcome after conservative treatment and no CIED infection was developed during follow-up.Conclusion: Clinicians should be aware of rare conditions that mimic CIED infection. Incorrect diagnosis of these disorders may falsely lead to CIED extraction. [ABSTRACT FROM AUTHOR]

Aims Epicardial structural abnormalities at the right ventricular outflow tract (RVOT) may provide the arrhythmia substrate in Brugada syndrome (BrS). Electroanatomical endocardial unipolar voltage mapping is an emerging tool that accurately identifies epicardial abnormalities in different clinical settings. This study investigated whether endocardial unipolar voltage mapping of the RVOT detects electroanatomical abnormalities in patients with BrS. Methods and results Ten asymptomatic patients (8 males, 34.5 ± 11.2 years) with spontaneous type 1 ECG pattern of BrS and negative late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-c-MRI) underwent high-density endocardial electroanatomical mapping (>800 points). Using a cut-off of 1 mV and 4 mV for normal bipolar and unipolar voltage, respectively, derived from 20 control patients without structural heart disease established by LGE-c-MRI, the extend of low-voltage areas within the RVOT was estimated using a specific calculation software. The mean RVOT area presenting low-voltage bipolar signals in BrS patients was 3.4 ± 1.7 cm2 (range 1.5–7 cm2). A significantly greater area of abnormal unipolar signals was identified (12.6 ± 4.6 cm2 [range 7–22 cm2], P : 0.001). Both bipolar and unipolar electroanatomical abnormalities were mainly located at the free wall of the RVOT. The mean RVOT activation time was significantly prolonged in BrS patients compared to control population (86.4 ± 16.5 vs. 63.4 ± 9.7 ms, P  < 0.001). Isochronal mapping demonstrated lines of conduction slowing within the RVOT in 8/10 BrS patients. Conclusion Wide areas of endocardial unipolar voltage abnormalities that possibly reflect epicardial structural abnormalities are identified at the RVOT of BrS patients. [ABSTRACT FROM AUTHOR]

Aims: Epicardial structural abnormalities at the right ventricular outflow tract (RVOT) may provide the arrhythmia substrate in Brugada syndrome (BrS). Electroanatomical endocardial unipolar voltage mapping is an emerging tool that accurately identifies epicardial abnormalities in different clinical settings. This study investigated whether endocardial unipolar voltage mapping of the RVOT detects electroanatomical abnormalities in patients with BrS.Methods and results: Ten asymptomatic patients (8 males, 34.5 ± 11.2 years) with spontaneous type 1 ECG pattern of BrS and negative late gadolinium enhancement-cardiac magnetic resonance imaging (LGE-c-MRI) underwent high-density endocardial electroanatomical mapping (>800 points). Using a cut-off of 1 mV and 4 mV for normal bipolar and unipolar voltage, respectively, derived from 20 control patients without structural heart disease established by LGE-c-MRI, the extend of low-voltage areas within the RVOT was estimated using a specific calculation software. The mean RVOT area presenting low-voltage bipolar signals in BrS patients was 3.4 ± 1.7 cm2 (range 1.5-7 cm2). A significantly greater area of abnormal unipolar signals was identified (12.6 ± 4.6 cm2 [range 7-22 cm2], P: 0.001). Both bipolar and unipolar electroanatomical abnormalities were mainly located at the free wall of the RVOT. The mean RVOT activation time was significantly prolonged in BrS patients compared to control population (86.4 ± 16.5 vs. 63.4 ± 9.7 ms, P < 0.001). Isochronal mapping demonstrated lines of conduction slowing within the RVOT in 8/10 BrS patients.Conclusion: Wide areas of endocardial unipolar voltage abnormalities that possibly reflect epicardial structural abnormalities are identified at the RVOT of BrS patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The prevalence of obesity is increasing among the general population. Obesity is associated with increased risk of several cardiovascular conditions, which in turn may increase the risk for atrial fibrillation (AF). We performed a meta‐analysis of cohort studies that examined the effect of obesity on the incidence of AF. In addition, we examined the effect of obesity on the incidence of AF stratified by gender. Methods and results: We searched the MEDLINE and EMBASE databases for studies evaluating the effect of obesity on AF. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model. Sixteen trials involving 587,372 subjects were included in the analysis. Obesity was defined as body mass index >30 kg/m2. AF during follow‐up developed in 5,751 of 91,031 (6.3%) obese subjects and in 15,346 of 496,341 (3.1%) nonobese subjects (RR = 1.51, 95% CI 1.35 to 1.68; P < 0.00001). Based on the pooled estimate across the studies, the effect of obesity on incident AF was similar in men (RR = 1.41, 95% 1.24 to 1.62; P < 0.00001) and women (RR = 1.53, 95% CI 1.19 to 1.97; P < 0.00001). Conclusion: Obesity is associated with an increased risk of new‐onset AF in susceptible individuals. This effect appears to be consistent in both genders. Further studies are warranted to examine the impact of weight loss interventions on the risk of developing AF. [ABSTRACT FROM AUTHOR]

Aims: The early repolarization (ER) pattern has been linked to an increased risk for arrhythmic death in various clinical settings. There are limited and conflicting data regarding the prognostic significance of ER pattern in Brugada syndrome (BS). The aim of this meta-analysis was to provide a detailed analysis of the currently available studies regarding the arrhythmic risk in patients with BS and ER pattern.Methods and results: Current databases were searched until May 2015. A random-effect meta-analysis of the effect of ER pattern on the incidence of arrhythmic events in patients with BS was performed. Five studies were included comprising a total of 1375 patients with BS. An ER pattern was reported in 177 patients (12.8%). During follow-up (44.9-93 months), 143 patients (10.4%) suffered an arrhythmic event. Overall, BS patients with ER pattern displayed an increased risk of arrhythmic events compared to patients without ER (OR 3.29, 95% CI: 2.06 to 5.26, P < 0.00001; Heterogeneity: P = 0.11, I2 = 48%). Three studies provided data regarding ER pattern location. Inferior, lateral, or inferolateral ER pattern location was observed in 20.3%, 32.2%, and 48%, respectively. An inferolateral ER location conferred the higher arrhythmic risk (OR 4.87, 95% CI: 2.64 to 9.01, P< 0.00001; Heterogeneity: P = 0.85, I2 = 0%).Conclusion: This meta-analysis suggests that the ER pattern is associated with a high risk of arrhythmic events in patients with BS. In particular, BS patients with inferolateral ER (global ER pattern) displayed the highest arrhythmic risk. [ABSTRACT FROM AUTHOR]

Brugada syndrome (BrS) is a primary electrical disease associated with increased risk of sudden cardiac death due to polymorphic ventricular arrhythmias. The prognosis, risk stratification, and management of asymptomatic individuals remain the most controversial issues in BrS. Furthermore, the decision to manage asymptomatic patients with an implantable cardioverter-defibrillator should be made after weighing the potential individual risk of future arrhythmic events against the risk of complications associated with the implant and follow-up of patients living with such devices, and the accompanying impairment of the quality of life. Several clinical, electrocardiographic, and electrophysiological markers have been proposed for risk stratification of subjects with BrS phenotype, but the majority have not yet been tested in a prospective manner in asymptomatic individuals. Recent data suggest that current risk factors are insufficient and cannot accurately predict sudden cardiac death events in this setting. This systematic review aims to discuss contemporary data regarding prognosis, risk stratification, and management of asymptomatic individuals with diagnosis of Brugada electrocardiogram pattern and to delineate the therapeutic approach in such cases. [ABSTRACT FROM AUTHOR]

Objectives: Implantable cardioverter defibrillators (ICDs) have a unique role for the primary and secondary prevention of sudden cardiac death (SCD). The aim of our systematic review is to present the existing data about the impact of statins on all-cause mortality and ICD interventions in heart failure (HF) patients who had an ICD implanted either for primary or for secondary prevention of SCD. Methods and results: We searched PubMed database and the reference list of the relevant studies for retrieving studies evaluating the effect of statins on all-cause mortality and ICD interventions in HF patients. We finally included 17 relevant studies in our systematic review. Of them, nine studies included data about the impact of statins on all-cause mortality, eight studies about the impact of statins on appropriate ICD interventions and three studies about the impact of statins on inappropriate ICD interventions in HF patients. These data showed that statins seem to have a beneficial role in the reduction of all-cause mortality and ICD interventions in HF patients. Conclusions: Statins seem to have a beneficial role in the reduction of all-cause mortality and ICD interventions in HF patients. However, further research about pleiotropic effects of statins is needed as well randomized control trials to elucidate the exact role of statin therapy in ICD outcomes. [ABSTRACT FROM AUTHOR]

Background/Aims Recent evidence indicates that peroxisome proliferator-activated receptor ( PPAR)-γ activators exert anti-inflammatory and antioxidant actions. However, the underlying mechanisms by which these agents prevent atrial remodeling in diabetes are not completely elucidated. We sought to investigate the potential effects of pioglitazone, a PPAR-γ activator, on atrial remodeling and atrial fibrillation ( AF) inducibility in diabetic rabbits. Methods Alloxan-induced diabetic rabbits were randomly divided into three groups: diabetes only, diabetes treated with low-dose pioglitazone (4 mg/day/kg), or diabetes treated with high-dose pioglitazone (8 mg/day/kg) (n=24 for each group). A total of 24 healthy rabbits served as controls. Eight weeks later, hemodynamic, echocardiographic, and electrophysiological parameters were recorded. Left atrial whole-cell patch-clamp studies, histological examination, and Western blot analysis were also performed. Results In the DM group (6/8 vs 1/8, P<.05), higher AF inducibility, increased amount of fibrosis, lower INa, and higher ICaL were observed in the DM group compared to controls. Western blot analysis showed that DM increased the expression of extracellular signal-regulated kinase 2 ( ERK2), phosphorylation ERK, transforming growth factor beta-1, Toll-like receptor 4, nuclear factor-κB p50, and heat-shock protein 70. All of these electrophysiological, histological, ion current density, and protein expression changes were all reduced by pioglitazone. Conclusion Pioglitazone attenuates diabetes-induced structural and electrophysiological remodeling in the atria, thereby reducing the vulnerability to AF. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that thiazolidinediones (TZDs) may exert protective effects in atrial fibrillation (AF). The present meta-analysis investigated the association between TZD use and the incidence of AF in diabetic patients.Methods: Electronic databases were searched until December 2016. Of the 346 initially identified records, 3 randomized clinical trials (RCTs) and 4 observational studies with 130,854 diabetic patients were included in the final analysis.Results: Pooled analysis of the included studies demonstrated that patients treated with TZDs had approximately 30% lower risk of developing AF compared to controls [odds ratio (OR): 0.73, 95% confidence interval (CI): 0.62 to 0.87, p = 0.0003]. This association was consistently observed for both new onset AF (OR =0.77, p = 0.002) and recurrent AF (OR =0.41, p = 0.002), pioglitazone use (OR =0.56, p = 0.04) but not rosiglitazone use (OR =0.78, p = 0.12). The association between TZD use and AF incidence was not significant in the pooled analysis of three RCTs (OR =0.77, 95% CI = 0.53-1.12, p = 0.17), but was significantly in the pooled analysis of the four observational studies (OR =0.71, p = 0.0003).Conclusions: This meta-analysis suggests that TZDs may confer protection against AF in the setting of diabetes mellitus (DM). This class of drugs can be used as upstream therapy for DM patients to prevent the development of AF. Further large-scale RCTs are needed to determine whether TZDs use could prevent AF in the setting of DM. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 67‐year old patient with ischemic cardiomyopathy had been implanted a single chamber implantable cardioverter defibrillator (ICD) for primary prevention in another center 1 month before the index event and possibly caused by lead dislocation to the level of the tricuspid annulus.

Background and Aim: Glycated hemoglobin (HbA1c) is a long-term measure of glucose control. Although recent studies demonstrated a potential association between HbA1c levels and the risk of atrial fibrillation (AF), the results have been inconsistent. The aim of this meta-analysis is to evaluate the utility of HbA1c level in predicting AF. Methods: PubMed and the Cochrane Library databases were searched for relevant studies up to March 2016. Prospective cohort studies and retrospective case-control studies were included. Relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) of AF development were determined for different HbA1c levels. The random effect model was conducted according to the test of heterogeneity among studies. Subgroup analyses and meta-regression models were carried out to identify potential sources of heterogeneity. Results: Eight prospective cohort studies with 102,006 participants and 6 retrospective case-control studies with 57,669 patients were finally included in the meta-analysis. In the primary meta-analysis, HbA1c levels were not associated with an increased risk of AF whether as a continuous (RR, 1.06; 95% CI, 0.96–1.18) or categorical variable (RR, 0.99; 95% CI, 0.83–1.18). Nevertheless, prospective studies showed about 10% increased risk of AF with elevated HbA1c levels both as a continuous (RR, 1.11; 95% CI, 1.06–1.16) and as a categorical variable (RR, 1.09; 95% CI, 1.00–1.18). In subgroup analyses, pooled results from studies with longer follow-up durations, published after 2012, aged < 63 years, with exclusion of cardiac surgery patients demonstrated an increased risk of AF for every 1% increase in HbA1c levels, while studies conducted in the United States with longer follow-up (more than 96 months), larger sample size and higher quality score (≥6) showed an increased risk of AF for higher HbA1c level as a categorical variable. Conclusions: Elevated serum HbA1c levels may be associated with an increased risk of AF, but further data are needed. Serum HbA1c levels might be considered as a potential biomarker for prediction of AF. [ABSTRACT FROM AUTHOR]

A significant increase in the implantation of cardiac implantable electronic devices (CIEDs) is evident over the past years, while there is evidence for a disproportionate increase in CIED-related infections. The cumulative probability of device infection seems to be higher in implantable cardioverter defibrillator and in cardiac resynchronization therapy patients compared with permanent pacemaker patients. Given that more than a half of CIED infections are possibly related to the operative procedure, there is a need for effective periprocedural infection control. However, many of the current recommendations are empirical and not evidence-based, while questions, unresolved issues, and conflicting evidence arise. The perioperative systemic use of antibiotics confers significant benefit in prevention of CIED infections. However, there are no conclusive data regarding the specific value of each agent in different clinical settings, the value of post-operative antibiotic treatment as well as the optimal duration of therapy. The merit of local pocket irrigation with antibiotic and/or antiseptic agents remains unproved. Of note, recent evidence indicates that the application of antibacterial envelopes into the device pocket markedly decreases the infection risk. In addition, limited reports on strict integrated infection control protocols show a dramatic reduction in infection rates in this setting and therefore deserve further attention. Finally, the relative impact of particular factors on the infection risk, including the type of the CIED, patients' individual characteristics and comorbidities, should be further examined since it may facilitate the development of tailored prophylactic interventions for each patient. [ABSTRACT FROM AUTHOR]