WITHDRAWN: Impact of Racial Differences on the Epidemiology and Clinical Outcomes of Atrial Fibrillation

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Spatial concentration and distribution of phase singularities in human atrial fibrillation: Insights for the AF mechanism.

BACKGROUND: Atrial fibrillation (AF) is characterized by the repetitive regeneration of unstable rotational events, the pivot of which are known as phase singularities (PSs). The spatial concentration and distribution of PSs have not been systematically investigated using quantitative statistical approaches. OBJECTIVES: We utilized a geospatial statistical approach to determine the presence of local spatial concentration and global clustering of PSs in biatrial human AF recordings. METHODS: 64-electrode conventional basket (~5 min, n = 18 patients, persistent AF) recordings were studied. Phase maps were produced using a Hilbert-transform based approach. PSs were characterized spatially using the following approaches: (i) local "hotspots" of high phase singularity (PS) concentration using Getis-Ord Gi* (Z ≥ 1.96, P ≤ .05) and (ii) global spatial clustering using Moran's I (inverse distance matrix). RESULTS: Episodes of AF were analyzed from basket catheter recordings (H: 41 epochs, 120 000 s, n = 18 patients). The Getis-Ord Gi* statistic showed local PS hotspots in 12/41 basket recordings. As a metric of spatial clustering, Moran's I showed an overall mean of 0.033 (95% CI: 0.0003-0.065), consistent with the notion of complete spatial randomness. CONCLUSION: Using a systematic, quantitative geospatial statistical approach, evidence for the existence of spatial concentrations ("hotspots") of PSs were detectable in human AF, along with evidence of spatial clustering. Geospatial statistical approaches offer a new approach to map and ablate PS clusters using substrate-based approaches.

Atrial fibrillation burden: an update-the need for a CHA2DS2-VASc-AFBurden score.

Atrial fibrillation (AF) is an established independent risk factor for stroke. Current guidelines regard AF as binary; either present or absent, with the decision for anti-coagulation driven by clinical variables alone. However, there are increasing data to support a biological gradient of AF burden and stroke risk, both in clinical and non-clinical AF phenotypes. As such, this raises the concept of combining AF burden assessment with a clinical risk score to refine and individualize the assessment of stroke risk in AF-the CHA2DS2VASc-AFBurden score. We review the published data supporting a biological gradient to try and construct a putative schema of risk attributable to AF burden.

Prospective cross-sectional study using Poisson renewal theory to study phase singularity formation and destruction rates in atrial fibrillation (RENEWAL-AF): Study design.

BACKGROUND: Unstable functional reentrant circuits known as rotors have been consistently observed in atrial fibrillation and are mechanistically believed critical to the maintenance of the arrhythmia. Recently, using a Poisson renewal theory-based quantitative framework, we have demonstrated that rotor formation (λf) and destruction rates (λd) can be measured using in vivo electrophysiologic data. However, the association of λf and λd with clinical, electrical, and structural markers of atrial fibrillation phenotype is unknown. METHODS: RENEWAL-AF is a multicenter prospective cross-sectional study recruiting adult patients with paroxysmal or persistent atrial fibrillation undergoing clinically indicated catheter ablation. Patients will undergo intraprocedural electrophysiologic atrial fibrillation mapping, with λf and λd to be determined from 2-minute unipolar electrogram recordings acquired before ablation. The primary objective will be to determine the association of λf and λd as markers of fibrillatory dynamics with clinical, electrical, and structural markers of atrial fibrillation clinical phenotype, measured by preablation transthoracic echocardiogram and cardiac magnetic resonance imaging. An exploratory objective is the noninvasive assessment of λf and λd using surface ECG characteristics via a machine learning approach. RESULTS: Not applicable. CONCLUSION: This pilot study will provide insight into the correlation between λf/λd with clinical, electrophysiological, and structural markers of atrial fibrillation phenotype and provide a foundation for the development of noninvasive assessment of λf/λd using surface ECG characteristics will help expand the use of λf/λd in clinical practice.

Multipolar mapping with the high-density grid catheter compared with conventional point-by-point mapping to guide catheter ablation for focal arrhythmias.

BACKGROUND: Multipolar catheters provide high-density mapping which may reduce the procedural duration and improve the success of catheter ablation (CA) for focal arrhythmias. The high-density grid (HDG) catheter is a 16 electrode mapping catheter with bipole recordings at orthogonal splines. The aim of this study is to compare the clinical and procedural features from a cohort who underwent CA for focal arrhythmias using multipolar mapping (MPM) with age and case-matched cohort using point-by-point (PbyP) mapping. METHODS: Consecutive patients undergoing CA for focal arrhythmias between October 2018 and January 2020 guided by MPM were compared with PbyP mapping with the ablation catheter over a similar period. Demographics, procedural features, and outcomes were compared. RESULTS: A total of 54 patients (27 in MPM vs. 27 in PbyP mapping) underwent CA for 68 focal arrhythmias (26 atrial and 42 ventricular). In the MPM group, the electrogram at the successful site was significantly earlier (39 ± 11 ms) than in the PbyP group (33 ± 7 ms; p = .02). In the MPM group, the mapping time (35 ± 24 vs. 53 ± 31 min in PbyP; p = .03) and procedural duration (126 ± 42 vs. 153 ± 39 min in PbyP; p = .02) were significantly shorter. There was no significant difference in radiofrequency and fluoroscopy times, acute procedural success, and arrhythmia recurrence. CONCLUSION: MPM with the HDG catheter for focal tachycardias identified earlier activation times and was associated with shorter mapping and procedure duration with equivalent success to PbyP mapping.

M/M/Infinity Birth-Death Processes - A Quantitative Representational Framework to Summarize and Explain Phase Singularity and Wavelet Dynamics in Atrial Fibrillation.

RATIONALE: A quantitative framework to summarize and explain the quasi-stationary population dynamics of unstable phase singularities (PS) and wavelets in human atrial fibrillation (AF) is at present lacking. Building on recent evidence showing that the formation and destruction of PS and wavelets in AF can be represented as renewal processes, we sought to establish such a quantitative framework, which could also potentially provide insight into the mechanisms of spontaneous AF termination. OBJECTIVES: Here, we hypothesized that the observed number of PS or wavelets in AF could be governed by a common set of renewal rate constants λ f (for PS or wavelet formation) and λ d (PS or wavelet destruction), with steady-state population dynamics modeled as an M/M/∞ birth-death process. We further hypothesized that changes to the M/M/∞ birth-death matrix would explain spontaneous AF termination. METHODS AND RESULTS: AF was studied in in a multimodality, multispecies study in humans, animal experimental models (rats and sheep) and Ramirez-Nattel-Courtemanche model computer simulations. We demonstrated: (i) that λ f and λ d can be combined in a Markov M/M/∞ process to accurately model the observed average number and population distribution of PS and wavelets in all systems at different scales of mapping; and (ii) that slowing of the rate constants λ f and λ d is associated with slower mixing rates of the M/M/∞ birth-death matrix, providing an explanation for spontaneous AF termination. CONCLUSION: M/M/∞ birth-death processes provide an accurate quantitative representational architecture to characterize PS and wavelet population dynamics in AF, by providing governing equations to understand the regeneration of PS and wavelets during sustained AF, as well as providing insight into the mechanism of spontaneous AF termination.

Transcatheter Transseptal Mitral Valve-in-Valve Replacement: An Early Australian Case Series and Literature Review.

BACKGROUND: Transcatheter mitral valve implantation for degenerated bioprostheses has recently emerged as an alternative to redo mitral valve surgery, particularly in patients at high risk for reoperative cardiac surgery. We sought to examine our early experience of transcatheter transseptal mitral valve-in-valve procedures. METHODS: Prospectively collected data was retrospectively reviewed in patients undergoing transcatheter transseptal mitral valve-in-valve implantation using the Edwards Sapien 3 balloon expandable bioprosthesis (Edwards Lifesciences, Irvine, CA, USA). RESULTS: Seven (7) patients underwent the procedure between December 2017 and November 2018. Three (3) patients were young Indigenous Australians (age range 33-41years) who were not suitable for mechanical prostheses; four patients were elderly (age range 82-92 years) and considered high risk for reoperative surgery. The median (maximum, minimum) EuroSCORE II of the group was 7.32 (4.81, 19.89). Procedural success was obtained in six of the seven patients; these six patients had no significant complications and had a median hospital stay of 3 days. In one patient, the device displaced towards the left ventricle on inflation, resulting in left ventricular outflow tract obstruction and haemodynamic instability. Urgent redo mitral valve surgery and explantation of the transcatheter prosthesis was undertaken, however, this patient died postoperatively of multi-organ failure. Of the successfully deployed valves, the median (maximum, minimum) gradient across the new mitral prosthesis was 5.5 mmHg (4, 7) and only one patient had mild mitral regurgitation, all others had no or trivial regurgitation. At 30 days, these six patients are well and all are in New York Heart Association (NYHA) Class I. CONCLUSIONS: Our early experience with transcatheter transseptal mitral valve-in-valve implantation demonstrates this procedure to be feasible in our institution with acceptable early results. Further follow-up is necessary to determine the longevity of valves implanted in this manner, especially in the younger population.

Is Atrial Fibrillation a Stroke Risk Factor or Risk Marker? An Appraisal Using the Bradford Hill Framework for Causality.

Atrial fibrillation (AF) is strongly associated with stroke risk but association on its own does not necessarily imply causality. Is AF a cause (risk factor) of stroke? Would treatment that reduces AF burden also reduce the burden of stroke? Or, perhaps, AF is a risk marker associated with a vascular syndrome in which there is co-existing atrial structural and electrical remodelling that results in the clinical manifestation of AF and the risk of stroke in parallel. A number of recent studies appear to detach AF as a direct cause of stroke. Studies in which cardiac implantable devices have been used to collect AF data preceding stroke appear to show no immediate temporal relationship. The Global Anticoagulant Registry in the Field - Atrial Fibrillation (GARFIELD-AF) a large worldwide registry of non-valvular AF, has shown that the risk of death exceeds the risk of stroke and that mortality, together with stroke and bleeding risk, is predicted by other vascular risk factors, defined by the CHA2DS2VASc score. Sir Bradford Hill proposed criteria to assess whether two associated factors are causal, more than 50 years ago. This method of analysing cause and effect in a complex scenario could be applied to AF and stroke. This paper aims to clinically appraise the evidence for each criterion outlined by Bradford Hill to single out whether the collective data supports one or the other.

Comparative spatial resolution of 12-lead electrocardiography and an automated algorithm.

BACKGROUND: The spatial resolution of pacemapping using 12-lead electrocardiography (ECG) or PaSo software is unknown. OBJECTIVE: The purpose of this study was to determine the spatial resolution of traditional ECG pacemapping and pacemapping using the PaSo coefficients. METHODS: Seventeen patients undergoing ablation of supraventricular tachycardias or atrioventricular node were included. After ablation, chamber (right ventricular outflow tract/rest of the right ventricle/left ventricle) geometry was created with Carto 3. Pacingwas performed from any point in these cardiac regions, the QRS morphology being the template and the point being considered as arrhythmia "origin." Subsequently, pacing was performed from points around the "origin" (1538 points). The QRS of these tagged points were compared by traditional ECG pacemapping and PaSo coefficients. The spatial resolution was calculated using correlations between the distance away from the origin (measured by 3 computational methods) and traditional ECG pacemapping and PaSo coefficients, independently. RESULTS: A 0.01-unit decrease in the PaSo coefficient resulted in 1.1 mm increased Cartesian distance (95% confidence interval [CI] 0.9-1.3 mm; P < .001) and 2.4 mm increased geodesic distance (95% CI 1.9-2.9 mm; P < .001) and 664 mm3 increase in convex hull volume (95% CI 423-906 mm3; P < .0001). For traditional ECG pacemapping, each decrease in lead match resulted in 1.7 mm increased Cartesian distance (95% CI 1.5-2.0 mm; P < .001) and 3.4 mm increased geodesic distance (95% CI 2.8-4.1 mm; P < .001) and 712 mm3 increase in convex hull volume (95% CI 599-830 mm3; P < .0001). Both PaSo coefficients and traditional pacemapping showed a significant inverse linear correlation with distance from the "origin." CONCLUSION: The resolution of mapping using the Paso software is better than that of traditional pacemapping.

Endothelial dysfunction and glycocalyx shedding in heart failure: insights from patients receiving cardiac resynchronisation therapy.

To determine (a) whether chronic heart failure with reduced ejection fraction (HFrEF) is associated with increased glycocalyx shedding; (b) whether glycocalyx shedding in HFrEF with left ventricular dyssynchrony is related to inflammation, endothelial dysfunction and/or redox stress and is ameliorated by cardiac resynchronisation therapy. Glycocalyx shedding has been reported to be increased in heart failure and is a marker of increased mortality. Its role in dyssynchronous systolic heart failure and the effects of cardiac resynchronisation therapy (CRT) are largely unknown. Twenty-six patients with dyssynchronous HFrEF were evaluated before and 6 months after CRT insertion. Echocardiographic septal to posterior wall delay (SPWD) assessed intra-ventricular mechanical dyssynchrony, and quality of life, integrity of nitric oxide (NO) signalling, inflammatory and redox-related biomarkers were measured. Glycocalyx shedding was quantitated via plasma levels of the glycocalyx component, syndecan-1. Syndecan-1 levels pre-CRT were inversely correlated with LVEF (r = - 0.45, p = 0.02) and directly with SPWD (r = 0.44, p = 0.02), QOL (r = 0.39, p = 0.04), plasma NT-proBNP (r = 0.43, p = 0.02), and the inflammatory marker, symmetric dimethylarginine (SDMA) (r = 0.54, p = 0.003). On multivariate analysis, syndecan-1 levels were predicted by SPWD and SDMA (ß = 0.42, p = 0.009 and ß = 0.54, p = 0.001, respectively). No significant correlation was found between syndecan-1 levels and other markers of endothelial dysfunction/inflammatory activation. Following CRT there was no significant change in syndecan-1 levels. In patients with dyssynchronous HFrEF, markers of glycocalyx shedding are associated with the magnitude of mechanical dyssynchrony and elevation of SDMA levels and inversely with LVEF. However, CRT does not reverse this process.

Complications of cardiac implantable electronic device placement in public and private hospitals.

BACKGROUND: Few safety data exist comparing clinical outcomes in Australian public and private hospitals. We hypothesised that differences could exist between public and private hospitals due to differences in acuity and patient-level co-morbidities. AIMS: To report comparative complications of cardiac implantable electronic device (CIED) placement in public and private hospitals. METHODS: We conducted an observational cohort study of outcomes of patients aged >18 years from 2010 to 2015 undergoing a new permanent pacemaker (PPM), implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy pacemaker or defibrillator (CRT-D/P) implant in NSW and Queensland public and private hospitals. The primary endpoint was major CIED-related complications occurring in-hospital or within 90 days of discharge. The independent effect of hospital sector was determined using multiple logistic regression, adjusting for covariates, including age, sex, co-morbidities and procedural acuity. RESULTS: A total of 32 364 new CIED implants (PPM 23 845, ICD 5361 and CRT-D/P 3158) were included (49% in private hospitals). Overall, 8.0% of private hospital procedures and 9.6% public hospital procedures experienced at least one complication. After adjustment, the overall risk of CIED complications was similar in private and public hospitals (OR: 0.92, 95% CI: 0.84-1.00, P = 0.06). In analysis of individual complications, adjusted all-cause in-hospital mortality was higher in private hospitals, (OR: 1.49, 95% CI: 1.03-2.16, P = 0.036) primarily driven by an excess mortality in acute cases. The adjusted risk of in-hospital generator operation (OR: 0.53, 95% CI: 0.30-0.94, P = 0.03) and post-discharge infection (OR: 0.61, 95% CI: 0.46-0.81, P < 0.001) was lower in private hospitals. CONCLUSIONS: These data identify important similarities and differences in safety outcomes of CIED implantation between Australian public and private hospitals.

Renewal Theory as a Universal Quantitative Framework to Characterize Phase Singularity Regeneration in Mammalian Cardiac Fibrillation.

BACKGROUND: Despite a century of research, no clear quantitative framework exists to model the fundamental processes responsible for the continuous formation and destruction of phase singularities (PS) in cardiac fibrillation. We hypothesized PS formation/destruction in fibrillation could be modeled as self-regenerating Poisson renewal processes, producing exponential distributions of interevent times governed by constant rate parameters defined by the prevailing properties of each system. METHODS: PS formation/destruction were studied in 5 systems: (1) human persistent atrial fibrillation (n=20), (2) tachypaced sheep atrial fibrillation (n=5), (3) rat atrial fibrillation (n=4), (5) rat ventricular fibrillation (n=11), and (5) computer-simulated fibrillation. PS time-to-event data were fitted by exponential probability distribution functions computed using maximum entropy theory, and rates of PS formation and destruction (λf/λd) determined. A systematic review was conducted to cross-validate with source data from literature. RESULTS: In all systems, PS lifetime and interformation times were consistent with underlying Poisson renewal processes (human: λf, 4.2%/ms±1.1 [95% CI, 4.0-5.0], λd, 4.6%/ms±1.5 [95% CI, 4.3-4.9]; sheep: λf, 4.4%/ms [95% CI, 4.1-4.7], λd, 4.6%/ms±1.4 [95% CI, 4.3-4.8]; rat atrial fibrillation: λf, 33%/ms±8.8 [95% CI, 11-55], λd, 38%/ms [95% CI, 22-55]; rat ventricular fibrillation: λf, 38%/ms±24 [95% CI, 22-55], λf, 46%/ms±21 [95% CI, 31-60]; simulated fibrillation λd, 6.6-8.97%/ms [95% CI, 4.1-6.7]; R2≥0.90 in all cases). All PS distributions identified through systematic review were also consistent with an underlying Poisson renewal process. CONCLUSIONS: Poisson renewal theory provides an evolutionarily preserved universal framework to quantify formation and destruction of rotational events in cardiac fibrillation.

Clinical safety of the ProMRI implantable cardioverter-defibrillator systems during head and lower lumbar magnetic resonance imaging at 3 T: results of the ProMRI 3T ENHANCED Master study.

AIMS: There have been no published studies on the safety of magnetic resonance imaging (MRI) at 3 Tesla (3 T) in patients with MRI-conditional implantable cardioverter-defibrillators (ICDs). The aim of this study was to assess clinical safety of the Biotronik ProMRI ICD system during non-diagnostic head and lower lumbar scans under 3 T MRI conditions. METHODS AND RESULTS: The study enrolled 129 patients at 12 sites in Australia, Singapore, and Europe. Predefined head and lower lumbar MR scans (total duration ≈30 min) were performed in 112 patients. Three primary endpoints were evaluated from the pre-MRI to the 1-month post-MRI visit: (i) freedom from serious adverse device effects (SADEs) related to MRI (hypothesized to be >90%); (ii) pacing threshold invariance for all leads (geometric mean of the patient-wise ratios for 1 month vs. pre-MRI was hypothesized to be <1.07); and (iii) sensing amplitude invariance (geometric mean of the ratios was hypothesized to be >0.993). No MRI-related SADE occurred (SADE-free rate 100%, 95% confidence interval 95.98-100%). Pacing threshold and sensing amplitudes fulfilled the invariance hypotheses with high statistical significance (P < 0.0013). No threshold increase >0.5 V or sensing amplitude decrease by >50% was observed (secondary endpoints). Lead impedances, battery capacity, and detection and treatment of arrhythmias by ICDs were not affected by MRI scans. CONCLUSION: The head and lower lumbar scans under specific 3 T MRI conditions were safe in the investigated MR-conditional ICD systems. There was no evidence of harm to the patients or any negative influence of the MRI scan on the implanted systems.

Long term prognostic importance of late gadolinium enhancement in first-presentation non-ischaemic dilated cardiomyopathy.

BACKGROUND: Presence of myocardial fibrosis in well-established non-ischaemic dilated cardiomyopathy (NIDCM) is associated with adverse clinical outcomes. However, the impact of myocardial fibrosis at first presentation in NIDCM, and its long-term association with left ventricular (LV) dysfunction, heart failure (HF) and ventricular arrhythmia (VA) remains unclear. We investigated whether the presence of myocardial fibrosis quantified by late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) at presentation, is independently associated with long-term major adverse cardiovascular events (MACE) in patients with first presentation NIDCM. METHODS: Consecutive patients with a first diagnosis of NIDCM were recruited. Patients underwent LGE-CMR at baseline. Replacement myocardial fibrosis by LGE-CMR was quantified by experienced observers blinded to patient outcome. MACE was defined as a composite end-point including cardiac death, HF rehospitalisation and the occurrence of sustained VA. RESULTS: Fifty-one patients with first presentation NIDCM were included, of which 49 (96%) had follow up and outcome data. Median follow up was 8.2 years. Both the LGE positive and LGE negative groups had similar clinical characteristics at follow up. In univariate Cox regression analysis, positive LGE was associated with MACE (HR:3.44; 95% CI:1.89 to 6.24, p-value < 0.001) and HF rehospitalisation (HR:2.89; 95% CI:1.42 to 5.85, p-value = 0.003). In multivariate Cox regression, positive LGE-CMR was independently associated with MACE (HR:3.53; 95% CI:1.51 to 8.27, p-value = 0.004) and HF rehospitalisation (HR:3.07; 95% CI:1.24 to 7.59, p-value = 0.015). CONCLUSIONS: The presence of myocardial fibrosis in first presentation NIDCM is independently associated with an increased risk of HF rehospitalisation, at long term follow-up.

Electrical remodelling post cardiac resynchronization therapy in patients with ischemic and non-ischemic heart failure.

BACKGROUND: The beneficial effects of cardiac resynchronization therapy (CRT) in heart failure are largely considered to be due to improved mechanical contractility. The contributory role of electrical remodelling is less clear. We sought to evaluate the impact of electrical remodelling in these patients. METHODS: 33 patients with conventional indications for CRT and with ischemic (ICM) (n = 17) and non-ischemic (NICM) (n = 16) aetiologies for heart failure were prospectively recruited. Functional parameters of peak exercise oxygen consumption (VO2max) and Minnesota quality of life (QOL) score, echocardiographic measures of LV functions and parameters of electrical remodelling, e.g. intrinsic QRS duration (iQRSD), intracardiac conduction times of LV pacing to RV electrocardiogram (LVp-RVegm), were measured at CRT implant and after 6 months. RESULTS: Only two electrical parameters predicted functional or symptomatic improvement. LVp-RVegm reduction significantly correlated with improvement in VO2max (r = -0.42, p = 0.03 while reduction in iQRSD significantly correlated with improvement in QOL score (r = 0.39, p = 0.04). The extent of changes in LVp-RVegm and iQRSD was significantly greater in NICM than in ICM patients (p = 0.017 and p = 0.042 for heterogeneity). There was also significant differential impact on QOL score in the NICM relative to the ICM group (p = 0.003) but none with VO2max. On multivariate analysis, only non-ischemic aetiology was a significant determinant of reduction in iQRSD. CONCLUSION: CRT induces potentially beneficial reduction in LVp-RVegm and iQRSD, which are seen selectively in NICM rather than ICM patients. The extent of improvement in these markers is associated with some functional and symptomatic measures of CRT efficacy.

Temporal stability and specificity of high bipolar electrogram entropy regions in sustained atrial fibrillation: Implications for mapping.

BACKGROUND: The potential utility of entropy (En) for atrial fibrillation (AF) mapping has been demonstrated in previous studies by multiple groups, where an association between high bipolar electrogram (EGM) entropy and the pivot of rotors has been shown. Though En is potentially attractive new approach to ablation, no studies have examined its temporal stability and specificity, which are critical to the application of entropy to clinical ablation. In the current study, we sought to objectively measure the temporal stability and specificity of bipolar EGM entropy in medium to long term recordings using three studies: i) a human basket catheter AF study, ii) a tachypaced sheep AF study and iii) a computer simulation study. OBJECTIVE: To characterize the temporal dynamics and specificity of Approximate, Sample and Shannon entropy (ApEn/SampEn/ShEn) in human (H), sheep (S), and computer simulated AF. METHODS: 64-electrode basket bi-atria sustained AF recordings (H:15 min; S:40 min) were separated into 5 s segments. ShEn/ApEn/SampEn were computed, and co-registered with NavX 3D maps. Temporal stability was determined in terms of: (i) global pattern stability of En and (ii) the relative stability the top 10% of En regions. To provide mechanistic insights into underlying mechanisms, stability characteristics were compared to models depicting various propagation patterns. To verify these results, cross-validation was performed across multiple En algorithms, across species, and compared with dominant frequency (DF) temporal characteristics. The specificity of En was also determined by looking at the association of En to rotors and areas of wave cross propagation. RESULTS: Episodes of AF were analysed (H:26 epochs, 6040 s; S:15 epochs, 14,160 s). The global pattern of En was temporally unstable (CV- H:13.42% ±â€¯4.58%; S:14.13% ±â€¯8.13%; Friedman- H: p > 0.001; S: p > 0.001). However, within this dynamic flux, the top 10% of ApEn/SampEn/ShEn regions were relatively temporally stable (Kappa >0.6) whilst the top 10% of DF regions were unstable (Kappa <0.06). In simulated AF scenarios, the experimental data were optimally reproduced in the context of an AF pattern with stable rotating waves surrounded by wavelet breakup (Kappa: 0.610; p < 0.0001). CONCLUSION: En shows global temporal instability, however within this dynamic flux, the top 10% regions exhibited relative temporal stability. This suggests that high En regions may be an appealing ablation target. Despite this, high En was associated with not just the pivot of rotors but also with areas of cross propagation, which suggests the need for future work before clinical application is possible.

Information Theory and Atrial Fibrillation (AF): A Review.

Atrial Fibrillation (AF) is the most common cardiac rhythm disorder seen in hospitals and in general practice, accounting for up to a third of arrhythmia related hospitalizations. Unfortunately, AF treatment is in practice complicated by the lack of understanding of the fundamental mechanisms underlying the arrhythmia, which makes detection of effective ablation targets particularly difficult. Various approaches to AF mapping have been explored in the hopes of better pinpointing these effective targets, such as Dominant Frequency (DF) analysis, complex fractionated electrograms (CFAE) and unipolar reconstruction (FIRM), but many of these methods have produced conflicting results or require further investigation. Exploration of AF using information theoretic-based approaches may have the potential to provide new insights into the complex system dynamics of AF, whilst also providing the benefit of being less reliant on empirically derived definitions in comparison to alternate mapping approaches. This work provides an overview of information theory and reviews its applications in AF analysis, with particular focus on AF mapping. The works discussed in this review demonstrate how understanding AF from a signal property perspective can provide new insights into the arrhythmic phenomena, which may have valuable clinical implications for AF mapping and ablation in the future.

Impact of Late Gadolinium Enhancement on mortality, sudden death and major adverse cardiovascular events in ischemic and nonischemic cardiomyopathy: A systematic review and meta-analysis.

BACKGROUND: The central role of left ventricular ejection fraction (LVEF) as the definitive risk marker of adverse outcomes in ischemic and nonischemic cardiomyopathy is increasingly uncertain. The current study aimed to conduct a systematic review and meta-analysis with the objective of evaluating the prognostic importance of Late Gadolinium Enhancement (LGE) in ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) on the key endpoints of all-cause mortality, cardiovascular mortality and sudden death. METHODS: The study was prospectively registered in PROPSERO (CRD 42016039034). Electronic databases and reference lists were searched for studies evaluating the impact of LGE-CMR on all-cause mortality, cardiovascular mortality, ventricular arrhythmia or sudden death, or major adverse cardiovascular events. Data were extracted from 36 studies including n=7882 patients. RESULTS: LGE was strongly associated with all-cause mortality HR 2.96 (95%CI: 2.37, 3.70, P<0.001), cardiovascular mortality HR 3.27 (95% CI: 2.05, 5.22, P<0.001), ventricular arrhythmia and sudden cardiac death HR 3.76 (95% CI: 3.14, 4.52, P<0.001), and major adverse cardiovascular events HR 3.24 (95% CI: 2.32, 4.52, P<0.001). In subgroup analyses, LGE was associated with all-cause mortality and cardiovascular mortality in both LVEF≤35% and LVEF>35% patients (P<0.001 all endpoints), as well as in nonischemic and ischemic cardiomyopathy. CONCLUSION: Late Gadolinium Enhancement (LGE) in CMR predicts all-cause mortality, cardiovascular mortality, ventricular arrhythmia and sudden death, and major adverse cardiovascular events, independent of LVEF. Future trials of investigational therapies in NICM and ICM should consider the utilization of LGE to identify patients at risk of adverse outcomes.