Felipe Atienza

Mechanisms of Wave Fractionation at Boundaries of High-Frequency Excitation in the Posterior Left Atrium of the Isolated Sheep Heart During Atrial Fibrillation

Background— High-frequency fractionated electrograms recorded during atrial fibrillation (AF) in the posterior left atrium (PLA) and elsewhere are being used as target sites for catheter ablation. We tested the hypothesis that highly periodic electric waves emerging from AF sources at or near the PLA give rise to the most fractionated activity in adjacent locations. Methods and Results— Sustained AF was induced in 8 isolated sheep hearts (0.5 &mgr;mol/L acetylcholine). Endocardial videoimaging (DI-4-ANEPPS) and electric mapping of the PLA enabled spatial characterization of dominant frequencies (DFs) and a regularity index (ratio of DF to total power). Regularity index showed that fractionation was lowest within the area with the maximal DF (DFmax domain; 0.19±0.02) and highest within a band of ≈3 mm (0.16±0.02; P=0.047) at boundaries with lower-frequency domains. The numbers of spatiotemporal periodic episodes (25.9±2.3) and rotors per experiment (1.9±0.7) were also highest within the DFmax domain. Most commonly, breakthrough waves at the PLA traveled toward the rest of the atria (76.8±8.1% outward versus 23.2±8.1% inward; P<0.01). In both experiments and simulations with an atrial ionic model, fractionation at DFmax boundaries was associated with increased beat-to-beat variability of conduction velocity and directionality with wavebreak formation. Conclusions— During stable AF, the PLA harbors regular, fast, and highly organized activity; the outer limit of the DFmax domain is the area where the most propagation pattern variability and fractionated activity occur. These new concepts introduce a new perspective in the clinical use of high-frequency fractionated electrograms to localize sources of AF precisely at the PLA and elsewhere.

Real-time dominant frequency mapping and ablation of dominant frequency sites in atrial fibrillation with left-to-right frequency gradients predicts long-term maintenance of sinus rhythm

BACKGROUND Spectral analysis identifies localized sites of high-frequency activity during atrial fibrillation (AF). OBJECTIVE This study sought to determine the effectiveness of using real-time dominant frequency (DF) mapping for radiofrequency ablation of maximal DF (DFmax) sites and elimination of left-to-right frequency gradients in the long-term maintenance of sinus rhythm (SR) in AF patients. METHODS DF mapping was performed in 50 patients during ongoing AF (32 paroxysmal, 18 persistent), acquiring a mean of 117 +/- 38 points. Ablation was performed targeting DFmax sites, followed by circumferential pulmonary vein isolation. RESULTS Ablation significantly reduced DFs (Hz) in the LA (7.9 +/- 1.4 vs. 5.7 +/- 1.3, P <.001), coronary sinus (CS) (5.7 +/- 1.1 vs. 5.3 +/- 1.2, P = .006), and RA (6.3 +/- 1.4 vs. 5.4 +/- 1.3, P <.001) abolishing baseline left-to-right atrial DF gradient (1.7 +/- 1.7 vs. 0.2 +/- 0.9; P <.001). Only a significant reduction in DFs in all chambers with a loss of the left-to-right atrial gradient after ablation was associated with a higher probability of long-term SR maintenance in both paroxysmal and persistent AF patients. After a mean follow-up of 9.3 +/- 5.4 months, 88% of paroxysmal and 56% of persistent AF patients were free of AF (P = .02). Ablation of DFmax sites was associated with a higher probability of remaining both free of arrhythmias (78% vs. 20%; P = .001) and free of AF (88% vs. 30%; P <.001). CONCLUSION Radiofrequency ablation leading to elimination of LA-to-RA frequency gradients predicts long-term SR maintenance in AF patients.

Tachycardia-Related Channel in the Scar Tissue in Patients With Sustained Monomorphic Ventricular Tachycardias Influence of the Voltage Scar Definition

Background—Endocardial mapping before sustained monomorphic ventricular tachycardia (SMVT) induction may reduce mapping time during tachycardia and facilitate the ablation of unmappable VT. Methods and Results—Left ventricular electroanatomic voltage maps obtained during right ventricular apex pacing in 26 patients with chronic myocardial infarction referred for VT ablation were analyzed to identify conducting channels (CCs) inside the scar tissue. A CC was defined by the presence of a corridor of consecutive electrograms differentiated by higher voltage amplitude than the surrounding area. The effect of different levels of voltage scar definition, from 0.5 to 0.1 mV, was analyzed. Twenty-three channels were identified in 20 patients. The majority of CCs were identified when the voltage scar definition was ≤0.2 mV. Electrograms with ≥2 components were recorded more frequently at the inner than at the entrance of CCs (100% versus 75%, P≤0.01). The activation time of the latest component was longer at the inner than at the entrance of CCs (200±40 versus 164±53 ms, P≤0.001). Pacing from these CCs gave rise to a long-stimulus QRS interval (110±49 ms). Radiofrequency lesion applied to CCs suppressed the inducibility in 88% of CC-related tachycardias. During a follow-up of 17±11 months, 23% of the patients experienced a VT recurrence. Conclusions—CCs represent areas of slow conduction that can be identified in 75% of patients with SMVT. A tiered decreasing-voltage definition of the scar is critical for CC identification.

Multicenter randomized trial of a comprehensive hospital discharge and outpatient heart failure management program.

Disease management programs can reduce hospitalizations in high‐risk heart failure (HF) patients, but generalizability to the population hospitalized for HF remains to be proven. We aimed to assess the effectiveness of a discharge and outpatient management program in a non‐selected cohort of patients hospitalized for HF.

Noninvasive Identification of Ventricular Tachycardia-Related Conducting Channels Using Contrast-Enhanced Magnetic Resonance Imaging in Patients With Chronic Myocardial Infarction Comparison of Signal Intensity Scar Mapping and Endocardial Voltage Mapping

OBJECTIVES We performed noninvasive identification of post-infarction sustained monomorphic ventricular tachycardia (SMVT)-related slow conduction channels (CC) by contrast-enhanced magnetic resonance imaging (ceMRI). BACKGROUND Conduction channels identified by voltage mapping are the critical isthmuses of most SMVT. We hypothesized that CC are formed by heterogeneous tissue (HT) within the scar that can be detected by ceMRI. METHODS We studied 18 consecutive VT patients (SMVT group) and 18 patients matched for age, sex, infarct location, and left ventricular ejection fraction (control group). We used ceMRI to quantify the infarct size and differentiate it into scar core and HT based on signal-intensity (SI) thresholds (>3 SD and 2 to 3 SD greater than remote normal myocardium, respectively). Consecutive left ventricle slices were analyzed to determine the presence of continuous corridors of HT (channels) in the scar. In the SMVT group, color-coded shells displaying ceMRI subendocardial SI were generated (3-dimensional SI mapping) and compared with endocardial voltage maps. RESULTS No differences were observed between the 2 groups in myocardial, necrotic, or heterogeneous mass. The HT channels were more frequently observed in the SMVT group (88%) than in the control group (33%, p < 0.001). In the SMVT group, voltage mapping identified 26 CC in 17 of 18 patients. All CC corresponded, in location and orientation, to a similar channel detected by 3-dimensional SI mapping; 15 CC were related to 15 VT critical isthmuses. CONCLUSIONS SMVT substrate can be identified by ceMRI scar heterogeneity analysis. This information could help identify patients at risk of VT and facilitate VT ablation.

Comparison of radiofrequency catheter ablation of drivers and circumferential pulmonary vein isolation in atrial fibrillation: a noninferiority randomized multicenter RADAR-AF trial.

BACKGROUND Empiric circumferential pulmonary vein isolation (CPVI) has become the therapy of choice for drug-refractory atrial fibrillation (AF). Although results are suboptimal, it is unknown whether mechanistically-based strategies targeting AF drivers are superior. OBJECTIVES This study sought to determine the efficacy and safety of localized high-frequency source ablation (HFSA) compared with CPVI in patients with drug-refractory AF. METHODS This prospective, multicenter, single-blinded study of 232 patients (age 53 ± 10 years, 186 males) randomized those with paroxysmal AF (n = 115) to CPVI or HFSA-only (noninferiority design) and those with persistent AF (n = 117) to CPVI or a combined ablation approach (CPVI + HFSA, superiority design). The primary endpoint was freedom from AF at 6 months post-first ablation procedure. Secondary endpoints included freedom from atrial tachyarrhythmias (AT) at 6 and 12 months, periprocedural complications, overall adverse events, and quality of life. RESULTS In paroxysmal AF, HFSA failed to achieve noninferiority at 6 months after a single procedure but, after redo procedures, was noninferior to CPVI at 12 months for freedom from AF and AF/AT. Serious adverse events were significantly reduced in the HFSA group versus CPVI patients (p = 0.02). In persistent AF, there were no significant differences between treatment groups for primary and secondary endpoints, but CPVI + HFSA trended toward more serious adverse events. CONCLUSIONS In paroxysmal AF, HFSA failed to achieve noninferiority at 6 months but was noninferior to CPVI at 1 year in achieving freedom of AF/AT and a lower incidence of severe adverse events. In persistent AF, CPVI + HFSA offered no incremental value. (Radiofrequency Ablation of Drivers of Atrial Fibrillation [RADAR-AF]; NCT00674401).

Mechanisms of Fractionated Electrograms Formation in the Posterior Left Atrium During Paroxysmal Atrial Fibrillation in Humans

OBJECTIVES The aim of this paper was to study mechanisms of formation of fractionated electrograms on the posterior left atrial wall (PLAW) in human paroxysmal atrial fibrillation (AF). BACKGROUND The mechanisms responsible for complex fractionated atrial electrogram formation during AF are poorly understood. METHODS In 24 patients, we induced sustained AF by pacing from a pulmonary vein. We analyzed transitions between organized patterns and changes in electrogram morphology leading to fractionation in relation to interbeat interval duration (systolic interval [SI]) and dominant frequency. Computer simulations of rotors helped in the interpretation of the results. RESULTS Organized patterns were recorded 31 ± 18% of the time. In 47% of organized patterns, the electrograms and PLAW activation sequence were similar to those of incoming waves during pulmonary vein stimulation that induced AF. Transitions to fractionation were preceded by significant increases in electrogram duration, spike number, and SI shortening (R(2) = 0.94). Similarly, adenosine infusion during organized patterns caused significant SI shortening leading to fractionated electrograms formation. Activation maps during organization showed incoming wave patterns, with earliest activation located closest to the highest dominant frequency site. Activation maps during transitions to fragmentation showed areas of slowed conduction and unidirectional block. Simulations predicted that SI abbreviation that heralds fractionated electrograms formation might result from a Doppler effect on wave fronts preceding an approaching rotor or by acceleration of a stationary or meandering, remotely located source. CONCLUSIONS During induced AF, SI shortening after either drift or acceleration of a source results in intermittent fibrillatory conduction and formation of fractionated electrograms at the PLAW.

Short- and long-term results of a programme for the prevention of readmissions and mortality in patients with heart failure : Are effects maintained after stopping the programme?

The objective of the study was to evaluate whether improvements obtained during an intervention programme were maintained after the programme was stopped. 153 patients discharged with a diagnosis of heart failure (HF) were randomized to either usual care or an intervention programme, which included patient education, consultation with the cardiologist and monitoring in the Heart Failure Unit. After an average period of 16±8 months, the intervention programme was stopped. One year later, all the patients were re‐examined to assess HF readmissions, all‐cause mortality, quality of life, and prescribed medical treatment. During the 16±8‐month treatment period, patients in the intervention group had a lower rate of HF readmissions (17% vs. 51%, p<0.01), less all‐cause mortality (13% vs. 27%, p=0.03), improvement in quality of life (1.5±0.8 vs. 1.9±1, p=0.03) and optimisation of medical treatment was achieved. One year after stopping the intervention, there was no difference in HF readmissions (28% vs. 25%, p=0.72), all‐cause mortality (14% vs. 17%, p=0.64) and quality of life (1.7±0.9 vs. 1.8±1, p=0.24) between the groups. Survival and the probability of not being readmitted due to HF were similar in both groups. There was also a reduction in the use of beta‐blockers and spironolactone in the intervention group.

Noninvasive Localization of Maximal Frequency Sites of Atrial Fibrillation by Body Surface Potential Mapping

Background—Ablation of high-frequency sources in patients with atrial fibrillation (AF) is an effective therapy to restore sinus rhythm. However, this strategy may be ineffective in patients without a significant dominant frequency (DF) gradient. The aim of this study was to investigate whether sites with high-frequency activity in human AF can be identified noninvasively, which should help intervention planning and therapy. Methods and Results—In 14 patients with a history of AF, 67-lead body surface recordings were simultaneously registered with 15 endocardial electrograms from both atria including the highest DF site, which was predetermined by atrial-wide real-time frequency electroanatomical mapping. Power spectra of surface leads and the body surface location of the highest DF site were compared with intracardiac information. Highest DFs found on specific sites of the torso showed a significant correlation with DFs found in the nearest atrium (&rgr;=0.96 for right atrium and &rgr;=0.92 for left atrium) and the DF gradient between them (&rgr;=0.93). The spatial distribution of power on the surface showed an inverse relationship between the frequencies versus the power spread area, consistent with localized fast sources as the AF mechanism with fibrillatory conduction elsewhere. Conclusions—Spectral analysis of body surface recordings during AF allows a noninvasive characterization of the global distribution of the atrial DFs and the identification of the atrium with the highest frequency, opening the possibility for improved noninvasive personalized diagnosis and treatment.

Body surface localization of left and right atrial high-frequency rotors in atrial fibrillation patients: A clinical-computational study

BACKGROUND Ablation is an effective therapy in patients with atrial fibrillation (AF) in which an electrical driver can be identified. OBJECTIVE The aim of this study was to present and discuss a novel and strictly noninvasive approach to map and identify atrial regions responsible for AF perpetuation. METHODS Surface potential recordings of 14 patients with AF were recorded using a 67-lead recording system. Singularity points (SPs) were identified in surface phase maps after band-pass filtering at the highest dominant frequency (HDF). Mathematical models of combined atria and torso were constructed and used to investigate the ability of surface phase maps to estimate rotor activity in the atrial wall. RESULTS The simulations show that surface SPs originate at atrial SPs, but not all atrial SPs are reflected at the surface. Stable SPs were found in AF signals during 8.3% ± 5.7% vs. 73.1% ± 16.8% of the time in unfiltered vs. HDF-filtered patient data, respectively (P < .01). The average duration of each rotational pattern was also lower in unfiltered than in HDF-filtered AF signals (160 ± 43 ms vs. 342 ± 138 ms; P < .01), resulting in 2.8 ± 0.7 rotations per rotor. Band-pass filtering reduced the apparent meandering of surface HDF rotors by reducing the effect of the atrial electrical activity occurring at different frequencies. Torso surface SPs representing HDF rotors during AF were reflected at specific areas corresponding to the fastest atrial location. CONCLUSION Phase analysis of surface potential signals after HDF filtering during AF shows reentrant drivers localized to either the left atrium or the right atrium, helping in localizing ablation targets.