Cardiac contractility modulation in patients with heart failure - A review of the literature.

Experimental in vivo and in vitro studies showed that electric currents applied during the absolute refractory period can modulate cardiac contractility. In preclinical studies, cardiac contractility modulation (CCM) was found to improve calcium handling, reverse the foetal myocyte gene programming associated with heart failure (HF), and facilitate reverse remodeling. Randomized control trials and observational studies have provided evidence about the safety and efficacy of CCM in patients with HF. Clinically, CCM therapy is indicated to improve the 6-min hall walk, quality of life, and functional status of HF patients who remain symptomatic despite guideline-directed medical treatment without an indication for cardiac resynchronization therapy (CRT) and have a left ventricular ejection fraction (LVEF) ranging from 25 to 45%. Although there are promising results about the role of CCM in HF patients with preserved LVEF (HFpEF), further studies are needed to elucidate the role of CCM therapy in this population. Late gadolinium enhancement (LGE) assessment before CCM implantation has been proposed for guiding the lead placement. Furthermore, the optimal duration of CCM application needs further investigation. This review aims to present the existing evidence regarding the role of CCM therapy in HF patients and identify gaps and challenges that require further studies.

Application of artificial intelligence in the diagnosis and treatment of cardiac arrhythmia.

The rapid growth in computational power, sensor technology, and wearable devices has provided a solid foundation for all aspects of cardiac arrhythmia care. Artificial intelligence (AI) has been instrumental in bringing about significant changes in the prevention, risk assessment, diagnosis, and treatment of arrhythmia. This review examines the current state of AI in the diagnosis and treatment of atrial fibrillation, supraventricular arrhythmia, ventricular arrhythmia, hereditary channelopathies, and cardiac pacing. Furthermore, ChatGPT, which has gained attention recently, is addressed in this paper along with its potential applications in the field of arrhythmia. Additionally, the accuracy of arrhythmia diagnosis can be improved by identifying electrode misplacement or erroneous swapping of electrode position using AI. Remote monitoring has expanded greatly due to the emergence of contactless monitoring technology as wearable devices continue to develop and flourish. Parallel advances in AI computing power, ChatGPT, availability of large data sets, and more have greatly expanded applications in arrhythmia diagnosis, risk assessment, and treatment. More precise algorithms based on big data, personalized risk assessment, telemedicine and mobile health, smart hardware and wearables, and the exploration of rare or complex types of arrhythmia are the future direction.

Radiofrequency versus cryoballoon catheter ablation in patients with persistent atrial fibrillation: A randomized trial.

INTRODUCTION: Patients with persistent atrial fibrillation (AF) represent a challenging population for rhythm control therapies. Catheter ablation (CA) with pulmonary vein isolation (PVI) is an effective treatment option for the reduction of the arrhythmic burden. Data regarding the comparability between radiofrequency (RF) and cryoballoon ablation (CRYO) in persistent AF are limited. METHODS: This is a prospective, randomized, single-center study designed to compare the efficacy in terms of rhythm control between RF and CRYO in persistent AF. Eligible participants were randomized 2:1 in two arms: RF and CRYO. The primary endpoint of the study was arrhythmia relapse in the early postprocedural period (first 3 months) and in the middle term follow-up (3 months to 12 months). Secondary endpoints included procedure duration, fluoroscopy time, and complications. RESULTS: A total of 199 patients participated in the study (133 patients in the RF arm, 66 in the CRYO arm). No statistically significant difference occurred between the two groups regarding the primary endpoint (recurrences ≤3 months: 35.5% RF vs. 37.9% CRYO, p .755, recurrences >3 months: 26.3% RF vs. 27.3% CRYO, p .999). From the secondary endpoints, CRYO was a procedure of significantly shorter duration (75.15 ± 17.21 in CRYO vs. 136.6 ± 43.33 in RF group, p < .05). CONCLUSION: CRYO and RF ablation appear to be equally effective for rhythm control in patients with persistent AF. CRYO ablation is advantageous in terms of procedure duration.

Association between sodium-glucose cotransporter-2 inhibitors and incident atrial fibrillation/atrial flutter in heart failure patients with reduced ejection fraction: a meta-analysis of randomized controlled trials.

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.

Phosphorus Magnetic Resonance Spectroscopy (31P MRS) and Cardiovascular Disease: The Importance of Energy.

Background and Objectives: The heart is the organ with the highest metabolic demand in the body, and it relies on high ATP turnover and efficient energy substrate utilisation in order to function normally. The derangement of myocardial energetics may lead to abnormalities in cardiac metabolism, which herald the symptoms of heart failure (HF). In addition, phosphorus magnetic resonance spectroscopy (31P MRS) is the only available non-invasive method that allows clinicians and researchers to evaluate the myocardial metabolic state in vivo. This review summarises the importance of myocardial energetics and provides a systematic review of all the available research studies utilising 31P MRS to evaluate patients with a range of cardiac pathologies. Materials and Methods: We have performed a systematic review of all available studies that used 31P MRS for the investigation of myocardial energetics in cardiovascular disease. Results: A systematic search of the Medline database, the Cochrane library, and Web of Science yielded 1092 results, out of which 62 studies were included in the systematic review. The 31P MRS has been used in numerous studies and has demonstrated that impaired myocardial energetics is often the beginning of pathological processes in several cardiac pathologies. Conclusions: The 31P MRS has become a valuable tool in the understanding of myocardial metabolic changes and their impact on the diagnosis, risk stratification, and prognosis of patients with cardiovascular diseases.

Global longitudinal strain predicts responders after cardiac resynchronization therapy-a systematic review and meta-analysis.

To evaluate the association between baseline global longitudinal strain (GLS) and ΔGLS (difference of baseline GLS and follow-up) and cardiac resynchronization therapy (CRT) response defined either with clinical or with echocardiographic characteristics. This meta-analysis was performed in accordance to both the Meta-Analysis of Observational Studies in Epidemiology and Strengthening the Reporting of Observational Studies in Epidemiology guidelines. Two independent investigators performed a comprehensive systematic search in MedLine, EMBASE and Cochrane databases through September 2019 without limitations. Data analysis was performed by using the Review Manager software (RevMan), version 5.3, and Stata 13 software. A p value of less than 0.05 (two-tailed) was considered statistically significant. Twelve studies (1004 patients, mean age 63.8 years old, males 69.4%) provided data on the association of baseline GLS with the response to CRT therapy. We found that CRT responders had significantly better resting GLS values compared with non-responders [GLS mean difference -2.13 (-3.03, -1.23), p < 0.001, I2 78%]. Furthermore, CRT responders had significantly greater improvement of GLS at follow-up compared with non-responders [ΔGLS mean difference -3.20 (-4.95, -1.45), p < 0.001, I2 66%]. These associations remained significant in a subgroup analysis including only studies with similar CRT response definition. In this meta-analysis, we found that CRT responders had a baseline and ΔGLS significantly higher than the non-responders strengthening the central role of GLS as a tool for selecting candidates for CRT. Furthermore, improved GLS values after CRT may be used to better define CRT responders.

Predictors of fatal arrhythmic events in patients with non-compaction cardiomyopathy: a systematic review.

Left ventricular non-compaction cardiomyopathy (LVNC) is a congenital heart disease with autosomal dominant inheritance. This review aims to summarize the existing data about the predictors of fatal arrhythmias in patients with LVNC. Medline and Cochrane library databases were searched from inception to November 2021 for articles on LVNC. The reference lists of the relevant research studies as well as the relevant review studies and meta-analyses were also searched. Clinical symptoms and electrocardiogram findings such as left bundle branch block are significantly associated with ventricular arrhythmias. Other non-invasive tools such as Holter monitoring, echocardiography, and cardiac magnetic resonance (CMR) can provide additional value for risk stratification. CMR-derived left and right ventricular ejection fraction, left ventricular end-diastolic diameter, late gadolinium enhancement, and non-compacted to compacted myocardium ratio are predictive of ventricular arrhythmias. An electrophysiological study can provide additional prognostic data in patients with LVNC who are at moderate risk of ventricular arrhythmias. Risk stratification of LVNC patients with no prior history of a fatal arrhythmic event remains challenging. Symptoms assessment, electrocardiogram, Holter monitoring, and cardiac imaging should be performed on every patient, while an electrophysiological study should be performed for moderate-risk patients. Large cohort studies are needed for the construction of score models for arrhythmic risk stratification purposes.

The role of cardiac magnetic resonance in identifying appropriate candidates for cardiac resynchronization therapy - a systematic review of the literature.

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.

Right ventricular outflow tract endocardial unipolar substrate mapping: implications in risk stratification of Brugada syndrome.

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.

Predictive risk models for forecasting arrhythmic outcomes in Brugada syndrome: A focused review.

Brugada syndrome (BrS) is a rare disorder characterized by coved or saddle-shaped ST-segment elevation in the right precordial leads on the electrocardiogram. Risk stratification in BrS remains challenging. A number of clinical, electrocardiographic, programmed ventricular stimulation and genetic risk factors have been identified as important predictors of future major arrhythmic events. There is a positive association between the number of risk factors and arrhythmic events. Hence, a multi-parametric approach would provide comprehensive risk assessment and more accurate risk stratification, assisting in therapeutic decisions making, including implantable cardioverter-defibrillator placement or identification of low-risk individuals. However, the extent to which each variable influences the risk and non-linear interactions between the different risk variables make risk stratification challenging. This paper aims to provide a focused review of the multi-parametric risk models for BrS risk stratification published in the literature.

Right ventricular outflow tract electroanatomical abnormalities in asymptomatic and high-risk symptomatic patients with Brugada syndrome: Evidence for a new risk stratification tool?

INTRODUCTION: Microstructural abnormalities at the epicardium of the right ventricular outflow tract (RVOT) may provide the arrhythmia substrate in Brugada syndrome (BrS). Endocardial unipolar electroanatomical mapping allows the identification of epicardial abnormalities. We evaluated the clinical implications of an abnormal endocardial substrate as perceived by high-density electroanatomical mapping (HDEAM) in patients with BrS. METHODS: Fourteen high-risk BrS patients with aborted sudden cardiac death (SCD) (12 males, mean age: 41.9 ± 11.8 years) underwent combined endocardial-epicardial HDEAM of the right ventricle/RVOT, while 40 asymptomatic patients (33 males, mean age: 42 ± 10.7 years) underwent endocardial HDEAM. Based on combined endocardial-epicardial procedures, endocardial HDEAM was considered abnormal in the presence of low voltage areas (LVAs) more than 1 cm2 with bipolar signals less than 1 mV and unipolar signals less than 5.3 mV. Programmed ventricular stimulation (PVS) was performed in all patients. RESULTS: The endocardial unipolar LVAs were colocalized with epicardial bipolar LVAs (p = .0027). Patients with aborted SCD exhibited significantly wider endocardial unipolar (p < .01) and bipolar LVAs (p < .01) compared with asymptomatic individuals. A substrate size of unipolar LVAs more than 14.5 cm2 (area under the curve [AUC]: 0.92, p < .001] and bipolar LVAs more than 3.68 cm2 (AUC: 0.82, p = .001) distinguished symptomatic from asymptomatic patients. Patients with ventricular fibrillation inducibility (23/54) demonstrated broader endocardial unipolar (p < .001) and bipolar LVAs (p < .001) than noninducible patients. The presence of unipolar LVAs more than 13.5 cm2 (AUC: 0.95, p < .001) and bipolar LVAs more than 2.97 cm2 (AUC: 0.78, p < .001) predicted a positive PVS. CONCLUSION: Extensive endocardial electroanatomical abnormalities identify high-risk patients with BrS. Endocardial HDEAM may allow risk stratification of asymptomatic patients referred for PVS.

Machine learning versus conventional clinical methods in guiding management of heart failure patients-a systematic review.

Machine learning (ML) algorithms "learn" information directly from data, and their performance improves proportionally with the number of high-quality samples. The aim of our systematic review is to present the state of the art regarding the implementation of ML techniques in the management of heart failure (HF) patients. We manually searched MEDLINE and Cochrane databases as well the reference lists of the relevant review studies and included studies. Our search retrieved 122 relevant studies. These studies mainly refer to (a) the role of ML in the classification of HF patients into distinct categories which may require a different treatment strategy, (b) discrimination of HF patients from the healthy population or other diseases, (c) prediction of HF outcomes, (d) identification of HF patients from electronic records and identification of HF patients with similar characteristics who may benefit form a similar treatment strategy, (e) supporting the extraction of important data from clinical notes, and (f) prediction of outcomes in HF populations with implantable devices (left ventricular assist device, cardiac resynchronization therapy). We concluded that ML techniques may play an important role for the efficient construction of methodologies for diagnosis, management, and prediction of outcomes in HF patients.

Use of high-density activation and voltage mapping in combination with entrainment to delineate gap-related atrial tachycardias post atrial fibrillation ablation.

AIMS: An incomplete understanding of the mechanism of atrial tachycardia (AT) is a major determinant of ablation failure. We systematically evaluated the mechanisms of AT using ultra-high-resolution mapping in a large cohort of patients. METHODS AND RESULTS: We included 107 consecutive patients (mean age: 65.7 ± 9.2 years, males: 81 patients) with documented endocardial gap-related AT after left atrial ablation for persistent atrial fibrillation (AF). We analysed the mechanism of 134 AT (94 macro-re-entries and 40 localized re-entries) using high-resolution activation mapping in combination with high-density voltage and entrainment mapping. Voltage in the conducting channels may be extremely low, even <0.1 mV (0.14 ± 0.095 mV, 51 of 134 AT, 41%), and almost always <0.5 mV (0.03-0.5 mV, 133 of 134 AT, 99.3%). The use of multipolar Orion, HDGrid, and Pentaray catheters improved our accuracy in delineating ultra-low-voltage areas critical for maintenance of the circuit of endocardial gap-related AT. Conventional ablation catheters often do not detect any signal (noise level) even using adequate contact force, and only multipolar catheters of small electrodes and shorter interelectrode space can detect clear fractionated low-amplitude and high frequency signals, critical for re-entry maintenance. We performed a diagnosis in 112 out of 134 AT (83.6%) using only activation mapping and in 134 out of 134 AT (100%) using the combination of activation and entrainment mapping. CONCLUSION: High-resolution activation mapping in combination with high-density voltage and entrainment mapping is the ideal strategy to delineate the critical part of the circuit in endocardial gap-related re-entrant AT after AF ablation.

Arrhythmias and electrocardiographic findings in Coronavirus disease 2019: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) primarily causes lung infection, but recent studies have shown that cardiac involvement is associated with a worse prognosis. OBJECTIVES: We conducted a systematic review and meta-analysis to examine the prevalence of cardiac arrhythmias detected by the electrocardiogram and their relationships with adverse outcomes in patients with COVID-19. METHODS: PubMed and Google were searched for studies that reported on cardiac arrhythmias and/or examined the relationship between arrhythmias and adverse outcomes. RESULTS: Thirty studies with 12,713 participants were included in the systematic review, and 28 studies (n = 12,499) in the meta-analysis. The mean age was 61.3 ± 16.8 years; 39.3% were female. In 25 studies with 7578 patients, the overall prevalence of cardiac arrhythmias was 10.3% (95% confidence interval [CI]: 8.4%-12.3%). The most common arrhythmias documented during hospitalization were supraventricular arrhythmias (6.2%, 95% CI: 4.4%-8.1%) followed by ventricular arrhythmias (2.5%, 95% CI: 1.8%-3.1%). The incidence of cardiac arrhythmias was higher among critically ill patients (relative risk [RR]: 12.1, 95% CI: 8.5-17.3) and among non-survivors (RR: 3.8, 95%, CI: 1.7-8.7). Eight studies reported changes in the QT interval. The prevalence of QTc > 500 ms was 12.3% (95% CI: 6.9%-17.8%). ST-segment deviation was reported in eight studies, with a pooled estimate of 8.7% (95% CI: 7.3% to 10.0%). CONCLUSION: Our meta-analysis showed that QTc prolongation, ST-segment deviation, and various other cardiac arrhythmias were observed in patients hospitalized with COVID-19. The presence of cardiac arrhythmias was associated with a worse prognosis.

Ligament of Marshall ablation for persistent atrial fibrillation.

Beyond pulmonary vein isolation, the two main additional strategies: Cox-Maze procedure or targeting of electrical signatures (focal bursts, rotational activities, meandering wavelets), remain controversial. High-density mapping of these arrhythmias has demonstrated firstly that a patchy lesion set is highly proarrhythmogenic, favoring macro-re-entry through conduction slowing and providing pivots for localized re-entry. Secondly, discrete anatomical structures such as the Vein or Ligament of Marshall (VOM/LOM) and the coronary sinus (CS) have epicardial muscular bundles that are more frequently involved in re-entry than previously thought. The Marshall Bundle can be ablated at any point along its course from the mid-to-distal coronary sinus to the left atrial appendage. If necessary, the VOM may be directly ablated using ethanol infusion to eliminate PV contributions and produce conduction block across the mistral isthmus. Ethanol ablation of the VOM, supplemented with RF ablation, may be more effective in producing conduction block at the mitral isthmus than repeat RF ablation alone.

KCNE2 gene mutation and Brugada syndrome.

KCNE2 gene mutations have been associated with atrial fibrillation, long QT syndrome, Brugada syndrome and unexplained sudden cardiac death. Herein, we describe a case of Brugada syndrome carrying an heterozygous variant in the KCNE2 gene [NM_172201.2:c.161 T > C, p.(Met54Thr, M54T)]. Gain of function of the Ito current possibly explains the Brugada ECG phenotype in this case.

Atrial substrate characterization in patients with atrial fibrillation and hypertrophic cardiomyopathy: Evidence for an extensive fibrotic disease.

INTRODUCTION: Data regarding the left atrial (LA) electroanatomical substrate in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) are missing. In this electroanatomical mapping (EAM) study, we evaluated the extent of LA fibrosis and its impact on catheter ablation outcomes in patients with HCM and AF. MATERIALS AND METHODS: High-density LA EAM was performed during AF in 28 consecutive patients with obstructive HCM and AF (42.9% displayed paroxysmal AF and 57.1% persistent AF). Propensity score (PS) matching analysis was performed to reduce the impact of potential confounding factors. PS were derived to match patients at a 1:1 ratio. Patients were matched according to age, sex and LA diameter. After PS, 28 non-HCM patients with AF were selected, and served as controls. Two different cut-off values of bipolar signal amplitude were investigated for fibrosis characterization (≤0.25 mV and ≤ 0.4 mV). HCM patients underwent pulmonary vein antral isolation (PVAI) and roof line, while non-HCM patients PVAI only. RESULTS: After the 3-month blanking period, 10 HCM patients (35.7%) displayed atrial arrhythmia recurrence. HCM patients with arrhythmia recurrence showed significantly greater low voltage areas defined as either bipolar voltage ≤0.25 mV (22.5 ± 10% vs. 5.5 ± 6.4%, p = 0.001) or ≤ 0.4 mV (32 ± 13.9% vs. 5.9 ± 5.1%, p < 0.001). The presence of low voltage areas ≤0.4 mV greater than 14.1% of the total LA area also predicted arrhythmia recurrence with excellent sensitivity (100%) and specificity (100%). Univariate analysis revealed that the extent of LA fibrosis was the only predictor of AF recurrence. After PS matching with non-HCM patients, patients with HCM exhibited wider fibrotic regions ≤0.25 mV compared to non-HCM patients (p = 0.016). CONCLUSIONS: High-density EAM reveals extensive LA fibrotic disease in patients with HCM, an event with certain implications in catheter ablation outcomes.

Contemporary Role of Cardiac Magnetic Resonance in the Management of Patients with Suspected or Known Coronary Artery Disease.

Cardiac magnetic resonance imaging (CMR) is a useful non-invasive radiation-free imaging modality for the management of patients with coronary artery disease (CAD). CMR cine imaging provides the "gold standard" assessment of ventricular function, late gadolinium enhancement (LGE) provides useful data for the diagnosis and extent of myocardial scar and viability, while stress imaging is an established technique for the detection of myocardial perfusion defects indicating ischemia. Beyond its role in the diagnosis of CAD, CMR allows accurate risk stratification of patients with established CAD. This review aims to summarize the data regarding the role of CMR in the contemporary management of patients with suspected or known coronary artery disease.

Atrial fibrillation in Brugada syndrome: Current perspectives.

The incidence of atrial fibrillation (AF) in Brugada syndrome (BrS) has been reported at between 9% and 53% by different series, but the true prevalence is unknown. However, AF may be the presenting feature in some patients. The underlying mechanisms for AF may be a combination of multiple factors, genetic or acquired, that may impact upon autonomic function, atrial structure, and conduction velocities or other unknown factors. The presence of AF has been associated with a more malignant course, with a greater incidence of syncope and ventricular arrhythmias, thus acting as marker of more advanced disease. Regarding the management of patients with AF, antiarrhythmic drugs effective in preventing malignant arrhythmias in BrS such as quinidine or invasive treatment with pulmonary vein isolation (PVI) may be useful in AF treatment. In this review, we aim to present the current perspectives regarding the genetics, pathophysiology, management, and prognosis of AF in patients with BrS.

Association of QRS narrowing with response to cardiac resynchronization therapy-a systematic review and meta-analysis of observational studies.

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.