[Show abstract][Hide abstract] ABSTRACT: Burden of atrial fibrillation (AF) can be reduced by ablation of sources of electrical impulses driving AF but driver identification is still challenging. This study presents a new methodology based on causality analysis that allows identifying the hierarchically dominant areas driving AF. Identification of dominant propagation patterns was achieved by computing causal relations between intracardiac multi-electrode catheter recordings of four paroxysmal AF patients during sinus rhythm, pacing and AF. In addition, realistic mathematical models of the atria during AF were used to validate the methodology both in the presence and absence of dominant frequency (DF) gradients. During electrical pacing, sources of propagation patterns detected by causality analysis were consistent with the location of the stimulating catheter. During AF, propagation patterns presented temporal variability, but a dominant direction accounted for significantly more propagations than other directions (49 ± 15% vs. 14 ± 13% or less, p < 0.01). Both in patients with a DF gradient and in mathematical models, causal maps allowed the identification of sites responsible for maintenance of AF. Causal maps allowed the identification of atrial dominant sites. In particular, causality analysis resulted in stable dominant cause-effect propagation directions during AF and could serve as a guide for performing ablation procedures in AF patients.
Full-text · Article · Feb 2016 · Annals of Biomedical Engineering
[Show abstract][Hide abstract] ABSTRACT: Rotor-guided ablation has opened new perspectives into the therapy of atrial fibrillation (AF). However, the dynamics and role of rotors in human AF are still controversial. In this review the current knowledge gained through research models and patient data that support the notion that rotors are key players in AF maintenance is summarized. We report and discuss the discrepancies regarding rotor prevalence and stability in the various studies, which can be attributed in part to methodological differences among mapping systems. Validation and improvement of current clinical electrophysiology mapping technologies will be crucial for developing mechanistic based selection and application of the best therapeutic strategy for individual AF patient, being it, pharmaceutical, ablative or other approach.
Full-text · Article · Jan 2016 · Cardiovascular Research
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Ablation of high dominant frequency (DF) sources in patients with atrial fibrillation (AF) is an effective treatment option for paroxysmal AF. The aim of this study was to evaluate the accuracy of noninvasive estimation of DF and electrical patterns determination by solving the inverse problem of the electrocardiography.
Four representative AF patients with left-to-right and right-to-left atrial DF patterns were included in the study. For each patient, intracardiac electrograms from both atria were recorded simultaneously together with 67-lead body surface recordings. In addition to clinical recordings, realistic mathematical models of atria and torso anatomy with different DF patterns of AF were used. For both mathematical models and clinical recordings, inverse-computed electrograms were compared to intracardiac electrograms in terms of voltage, phase and frequency spectrum relative errors.
Comparison between intracardiac and inverse computed electrograms for AF patients showed 8.8 ± 4.4% errors for DF, 32 ± 4% for voltage and 65 ± 4% for phase determination. These results were corroborated by mathematical simulations showing that the inverse problem solution was able to reconstruct the frequency spectrum and the DF maps with relative errors of 5.5 ± 4.1%, whereas the reconstruction of the electrograms or the instantaneous phase presented larger relative errors (i.e. 38 ±15% and 48 ± 14 % respectively, p<0.01).
Noninvasive reconstruction of atrial frequency maps can be achieved by solving the inverse problem of electrocardiography with a higher accuracy than temporal distribution patterns. This article is protected by copyright. All rights reserved.
Full-text · Article · Jan 2016 · Journal of Cardiovascular Electrophysiology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Many centers perform catheter ablation for atrial fibrillation (AF) with periprocedural interruption of oral vitamin K antagonists. In this scenario, the optimal post-procedural anticoagulation strategy is still under debate. We sought to compare the incidence of major complications associated with post-procedural use of low molecular weight heparin (LMWH) versus unfractioned heparin (UFH) as a bridge to reinitiation of oral anticoagulation after an AF ablation procedure.
We retrospectively reviewed medical history data of all patients undergoing catheter ablation for AF at three Spanish referral centers between January 2009 and January 2014. A total of 702 patients were included in the analysis. We compared the incidence of major complications (a combination of major bleeding and thromboembolic events) between patients receiving UFH (291) and those receiving LMWH (411) after the procedure.
The overall incidence of major complications was 4.1 %, including five thromboembolic events (0.7 %) and 24 major bleeding events (3.4 %), with no significant differences in patients treated with LMWH vs. UFH (2.9 vs. 4.1 %; P = NS). The presence of peripheral vascular disease emerged as the only independent predictor of major complications (adjusted odds ratio (OR) 9.1; confidence interval (CI) 95 % 1.7-49.3; P < 0.01).
Immediate post-procedural bridging with UFH or with LMWH are equally safe strategies in patients undergoing catheter ablation for AF in whom oral anticoagulation is interrupted for the procedure. Due to its greater simplicity of use, LMWH may be the preferred option. The presence of peripheral vascular disease is a potent predictor of major post-procedural complications.
No preview · Article · Jan 2016 · Journal of Interventional Cardiac Electrophysiology
[Show abstract][Hide abstract] ABSTRACT: The objective of this article is to present an in-vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1±1.3 and 9.7±0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e. relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in non-fibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in-vitro fibrillation (e.g. density of phase singularities (PS/cm2), dominant frequency and rotor meandering) analyzed by means of optical mapping were compared with the degree of electrophysiologic remodeling. Fibrillating cell cultures showed a differential ion channels gene expression associated with atrial tissue remodeling (i.e. decreased SCN5A, CACN1C, KCND3 and GJA1 and increased KCNJ2) not present in non-fibrillating cell cultures. Also, fibrillatory complexity was increased in late vs. early stage cultures (1.12±0.14 vs. 0.43±0.19 PS/cm(2), p<0.01) which was associated with changes in the electrical reentrant patterns (i.e. decrease in rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF.
[Show abstract][Hide abstract] ABSTRACT: -Differential diagnosis between tachycardia mediated by septal accessory pathways (AP) and atypical atrioventricular nodal reentry (AVNRT) can be challenging. We hypothesized that an immediate versus delayed pace-related advancement of the atrial electrogram, once the local septal parahisian ventricular electrogram (SVE) has been advanced, may help in this diagnosis.
-We focused on differential timing between the SVE and atrial signals at the initiation of continuous right ventricular apical (RVA) pacing during tachycardia. SVE advancement preceding atrial reset was defined as SVE advanced by the paced wave fronts while atrial signal continued at the tachycardia cycle. We analyzed 51 atypical AVNRT (45% posterior type) and 80 AP tachycardias (anteroseptal , parahisian , midseptal  and posteroseptal ). SVE advancement preceding atrial reset was observed in 98% of AVNRTs during 4±1.1 cycles; this phenomena was observed in 6 (8%) of the atrioventricular reentrant tachycardia (AVRT) mediated by septal AP (p<0.001; sensitivity 98%; specificity 93%; positive predictive value [PPV] 90%; negative predictive value [NPV] 99%), and lasted 1 single cycle (p<0.001). Right posteroseptal AP tachycardias were distinctly characterized by atrial reset preceding SVE advancement (with ventricular fusion; specificity 100%; PPV 100%). In 11 cases it was impossible to achieve sustain entrainment. In all of them, the differential responses at the entrainment attempt allowed for appropriate diagnosis.
-The differential response of the SVE and the atrial electrogram at the initiation of continuous RVA pacing during tachycardia effectively distinguishes between atypical AVNRT and AVRT mediated by septal APs.
[Show abstract][Hide abstract] ABSTRACT: -Ventricular fibrillation (VF) has been proposed to be maintained by localized high-frequency sources. We tested whether spectral-phase analysis of the precordial ECG enabled identification of periodic activation patterns generated by such sources.
-Precordial ECGs were recorded from 15 Ischemic Cardiomyopathy (IC) and 15 Brugada Syndrome (BrS type-1 ECG) patients during induced VF, and analyzed in the frequency-phase domain. Despite temporal variability, induced VF episodes lasting 19.6±7.9 sec displayed distinctly high power at a common frequency (Shared Frequency; SF=5.7±1.1 Hz) in all leads about half of the time. In BrS patients, phase analysis of SF showed a V1-to-V6 sequence as would be expected from patients displaying a type-1 ECG pattern (p<0.001). Hilbert-based phases confirmed that the most stable sequence over the whole VF duration was V1 to V6. Analysis of SF in IC patients with anteroseptal (n=4), apical (n=3) and inferolateral (n=4) myocardial infarction displayed a sequence starting at V1-V2, V3-V4 and V5-V6, respectively, consistent with an activation origin at the scar location (p=0.005). Sequences correlated with the Hilbert-based phase analysis (p<0.001). Posterior infarction (n=4) displayed no specific sequence. On paired comparison phase sequences during monomorphic ventricular tachycardia (VT) correlated moderately with VF (p<0.001). Moreover, there was a dominant frequency gradient from precordial leads facing the scar region to the contralateral leads (5.8±0.8 vs. 5.4±1.1 Hz; p=0.004).
-Non-invasive analysis of VT and early VF in BrS and IC patients shows a predictable sequence in the frequency-phase domain, consistent with anatomical location of the arrhythmogenic substrate.
Full-text · Article · Aug 2015 · Circulation Arrhythmia and Electrophysiology
[Show abstract][Hide abstract] ABSTRACT: AbstractObjectives To determine if non-invasive measurement of scar by contrast-enhanced magnetic resonance imaging (ceMRI)-based signal intensity (SI) mapping predicts VT recurrences after endocardial ablation. Background Scar extension on voltage mapping predicts ventricular tachycardia (VT) recurrences after ablation procedures. Methods We included 46 consecutive patients with previous myocardial infarction (87% male, age 68±9 years, LVEF 36±10%), who underwent VT substrate ablation before implanting a cardioverter-defibrillator. Prior to ablation, a ceMRI was obtained and the areas of endocardial and epicardial scars and heterogeneous tissue (HT) were measured: the averaged subendocardial and subepicardial SI were projected onto 3D endocardial and epicardial shells in which dense scar, HT and normal tissue were differentiated. Results During a mean follow-up of 32±24 months 17 patients (37%) presented VT recurrences. Patients with recurrences had larger scar and HT areas in SI maps both in endocardium (81±27 vs 48±21 cm2, p=0.001 and 53±21 vs 30±15 cm2, p=0.001 respectively) and epicardium (76±28 vs 51±29 cm2, p=0.032 and 59±25 vs 37±19 cm2, p=0.008). In the multivariate analysis MRI endocardial scar extension was the only independent predictor of VT recurrence (hazard ratio 1.310 [per 10 cm2], 95% confidence interval 1.051-1.632, p=0.034). Freedom from VT recurrence was higher in patients with small MRI endocardial scars (<65 cm2) as compared to those with larger scars (≥65 cm2) (85% vs 20%, log-rank p=0.018). Conclusions Pre-procedure endocardial scar extension assessment by ceMRI predicts VT recurrence after endocardial substrate ablation. This information may be useful to select patients for ablation procedures.
Full-text · Article · Aug 2015 · JACC Clinical Electrophysiology
[Show abstract][Hide abstract] ABSTRACT: Current indications for implantable cardioverter defibrillators (ICDs) in patients with channelopathies and cardiomyopathies of non-ischemic origin are mainly based on non-randomized evidence. In patients with nonischemic dilated cardiomyopathy (NIDCM) there is a tendency towards a beneficial effect on total mortality of ICD therapy in patients with significant left ventricular (LV) dysfunction. Although an important reduction in sudden cardiac death (SCD) seems to be clearly demonstrated in these patients, a net beneficial effect on total mortality is unclear mostly in cases with good functional status. Risk stratification has been changing over the last two decades in patients with hypertrophic cardiomyopathy (HCM). Its risk profile has been delineated in parallel with the beneficial effect of ICD in high risk patients. Observational results based on "appropriate" ICD interventions does support its usefulness both in primary and secondary SCD prevention in these patients. Novel risk models quantify the rate of sudden cardiac death in these patients on individual basis. Less clear risk stratification is available for cases of arrhythmogenic right ventricular cardiomyopathy (ARVC) and in other uncommon familiar cardiomyopathies. Main features of risk stratification vary among the different channelopathies (long QT syndrome -LQTS-, Brugada syndrome, etc) with great debate on the management of asymptomatic patients. For most familiar cardiomyopathies ICD therapy is the only accepted strategy in the prevention of SCD. So far, genetic testing has a limited role in risk assessment and management of the individual patient. This review aims to summarize these criticisms and to refine the current indications of ICD implantation in patients with cardiomyopathies and major channelopathies.
No preview · Article · Apr 2015 · Reviews on Recent Clinical Trials
[Show abstract][Hide abstract] ABSTRACT: Rivaroxaban is a once-daily oral anticoagulant currently marketed for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. This indication is largely based on the results of the ROCKET-AF trial. Although these results are robust, studies performed in clinical practice are necessary to confirm these data in real-life patients. These studies have shown rates of stroke and bleeding similar to that found in ROCKET-AF. As an anticoagulant, attention should be paid to making a correct prescription of rivaroxaban, particularly in fragile patients, to reduce the risk of bleeding. In addition, a number of studies have shown that rivaroxaban is cost-effective in clinical practice. Moreover, rivaroxaban is a good alternative to warfarin in patients undergoing elective cardioversion or atrial fibrillation ablation.
[Show abstract][Hide abstract] ABSTRACT: Experimental and clinical data demonstrate that atrial fibrillation (AF) maintenance in animals and groups of patients depends on localized reentrant sources localized primarily to the pulmonary veins (PVs) and the left atrium(LA) posterior wall in paroxysmal AF but elsewhere, including the right atrium (RA), in persistent AF. Moreover, AF can be eliminated by directly ablating AF-driving sources or "rotors," that exhibit high-frequency, periodic activity. The RADAR-AF randomized trial demonstrated that an ablation procedure based on a more target-specific strategy aimed at eliminating high frequency sites responsible for AF maintenance is as efficacious as and safer than empirically isolating all the PVs. In contrast to the standard ECG, global atrial noninvasive frequency analysis allows non-invasive identification of high-frequency sources before the arrival at the electrophysiology laboratory for ablation. Body surface potential map (BSPM) replicates the endocardial distribution of DFs with localization of the highest DF (HDF) and can identify small areas containing the high-frequency sources. Overall, BSPM had a sensitivity of 75% and specificity of 100% for capturing intracardiac EGMs as having LARA DF gradient. However, raw BSPM data analysis of AF patterns of activity showed incomplete and instable reentrant patterns of activation. Thus, we developed an analysis approach whereby a narrow band-pass filtering allowed selecting the electrical activity projected on the torso at the HDF, which stabilized the projection of rotors that potentially drive AF on the surface. Consequently, driving reentrant patterns ("rotors") with spatiotemporal stability during >70% of the AF time could be observed noninvasibly after HDF-filtering. Moreover, computer simulations found that the combination of BSPM phase mapping with DF analysis enabled the discrimination of true rotational patterns even during the most complex AF. Altogether, these studies show that the combination of DF analysis with phase maps of HDF-filtered surface ECG recordings allows noninvasive localization of atrial reentries during AF and further a physiologically-based rationale for personalized diagnosis and treatment of patients with AF.
No preview · Article · Mar 2015 · Cardiac electrophysiology clinics
[Show abstract][Hide abstract] ABSTRACT: Introduction: Myocardial fibrosis plays an important role in the pathogenesis of atrial fibrillation (AF). However, catheter ablation may eliminate AF sources but also increases fibrosis. We aimed to assess the predictive value of circulating biomarkers of collagen metabolism following AF catheter ablation.Methods: Serum levels (ELISA) of biomarkers of collagen metabolism were analyzed in patients undergoing AF ablation (62 paroxysmal, 67 persistent) at baseline and 12 months after ablation. Biomarkers levels in 20 patients in sinus rhythm were also evaluated to establish the normal values.Results: Before ablation, there was a direct linear correlation between PICP (carboxy-terminal propeptide of procollagen type I) levels and left atrial diameter for the overall sample (p=0.006). PICP levels at baseline were lower in paroxysmal AF patients with vs. without AF recurrences following ablation (68.30 ± 9.66μg/l vs 90.72 ± 3.78μg/l; p=0.017). At 12 months following ablation of paroxysmal patients, PICP le
[Show abstract][Hide abstract] ABSTRACT: Atrial fibrillation (AF) results in a remodeling of the electrical and structural characteristics of the cardiac tissue which dramatically reduces the efficacy of pharmacological and catheter-based ablation therapies. Recent experimental and clinical results have demonstrated that the complexity of the fibrillatory process significantly differs in paroxysmal versus persistent AF; however, the lack of appropriate research models of remodeled atrial tissue precludes the elucidation of the underlying AF mechanisms and the identification of appropriated therapeutic targets. Here, we summarize the different research models used to date, highlighting the lessons learned from them and pointing to the new doors that should be open for the development of innovative treatments for AF.
Full-text · Article · Nov 2014 · Expert Review of Cardiovascular Therapy
[Show abstract][Hide abstract] ABSTRACT: Background: Ventricular fibrillation is routinely induced during implantable cardioverter- -defibrillator insertion to assess defibrillator performance, but this strategy is experiencing a progressive decline. We aimed to assess the efficacy of defibrillator therapies and long-term outcome in a cohort of patients that underwent defibrillator implantation with and without defibrillation testing. Methods: Retrospective observational series of consecutive patients undergoing initial defibrillator insertion or generator replacement. We registered spontaneous ventricular arrhythmias incidence and therapy efficacy, and mortality. Results: A total of 545 patients underwent defibrillator implantation (111 with and 434 without defibrillation testing). After 19 (range 9–31) months of follow-up, the death rate per observation year (4% vs. 4%; p = 0.91) and the rate of patients with defibrillator-treated ventricular arrhythmic events per observation year (with test: 10% vs. without test: 12%; p = 0.46) were similar. The generalized estimating equations-adjusted first shock probability of success in patients with test (95%; CI 88–100%) vs. without test (98%; CI 96–100%; p = 0.42) and the proportion of successful antitachycardia therapies (with test: 87% vs. without test: 80%; p = 0.35) were similar between groups. There was no difference in the annualized rate of failed first shock per patient and per shocked patient between groups (5% vs. 4%; p = 0.94). Conclusions: In this observational study, that included an unselected population of patients with a defibrillator, no difference was found in overall mortality, first shock efficacy and rate of failed shocks regardless of whether defibrillation testing was performed or not.
[Show abstract][Hide abstract] ABSTRACT: Introduction: The role of tissue remodeling in the reentrant activity during atrial fibrillation (AF) is not well understood. The aim of this study is to evaluate in an in-vitro model of AF the role of tissue remodeling in the mechanisms of perpetuation of this arrhythmia.
Methods: HL-1 cultures were obtained for early stage (6.1 ± 1.3 days in culture, N=10) and late stage (11.7 ± 0.5 days in culture, N=8) AF. Bright field images together with optical calcium mapping (Rhod-2AM staining) were obtained for evaluating remodeling and electrophysiological characteristics of cell cultures.
Results: The number of singularity points per square centimeter at baseline was significantly higher in the late stage group (i.e. 0.43±0.19 vs. 1.12±0.14 PS/cm2, p <0.01) and showed an inverse correlation with the degree of homogeneity in the corresponding bright field microscopy images (R2=0.78, p <0.01) (Fig.1). These results demonstrate that the electrical complexity in the dish increased with the culture time. Rotor dynamics (i.e. curvature and rotor movement) were significantly correlated with the amount of PSs in the cultures (R2=0.86 and R2=0.79 respectively, Fig. 1).
Conclusion: Early and late stage HL-1 cell cultures present different degrees of electrophysiological complexity. Dynamics of functional reentries may be the main responsible for the increased complexity of remodeled cell cultures.
Full-text · Article · Jul 2014 · Cardiovascular Research