Decrement Evoked Potential (DEEP) Mapping of the Atria: Unmasking Atrial Fibrillation Substrate.

BACKGROUND: Atrial myopathy may underlie the progression of atrial fibrillation (AF) from a treatable disease to an irreversible condition with poor ablation outcomes. Electrophysiological methods to unmask areas prone to re-entry initiation could be key to defining latent atrial myopathy. METHODS: Consecutive patients referred for AF ablation were prospectively included at four institutions. Decrement evoked potential mapping (DEEP) was performed in eight left atrial sites and five right atrial sites, from two different pacing locations (endocardially from the left atrial appendage, epicardially from the proximal coronary sinus). The electrograms (EGMs) during S1 600 ms drive and after an extra stimulus (S2 at +30 ms above atrial refractoriness) were studied at each location and assessed for decremental properties. Follow-up was 12 months. RESULTS: Seventy-four patients were included and 85% had persistent AF. A total of 17,614 EGMs were individually analysed and measured. Nine percent of the EGMs showed DEEP properties (local delay of >10 ms after S2) with a mean decrement of 33±26 ms. DEEPs were more frequent in the left atrium than the right atrium (9.4% vs 8.0%; p<0.001) and more prevalent in persistent AF patients than paroxysmal AF patients (9.8% vs 4.6% p=0.001). Atrial DEEPs were more frequently unmasked in normal bipolar voltage areas and by epicardial pacing than endocardial pacing (9.6% vs 8.4%, respectively; p=0.004). Within the left atrium, the roof had the highest prevalence of DEEP EGMs. CONCLUSIONS: DEEP mapping of both atria is useful for highlighting areas with a tendency for unidirectional block and re-entry initiation. Those areas are more easily unmasked by epicardial pacing from the coronary sinus and more prevalent in persistent AF patients than in paroxysmal AF patients.

Panoramic Endocardial Optical Mapping Demonstrates Serial Rotors Acceleration and Increasing Complexity of Activity During Onset of Cholinergic Atrial Fibrillation.

Background Activation during onset of atrial fibrillation is poorly understood. We aimed at developing a panoramic optical mapping system for the atria and test the hypothesis that sequential rotors underlie acceleration of atrial fibrillation during onset. Methods and Results Five sheep hearts were Langendorff perfused in the presence of 0.25 µmol/L carbachol. Novel optical system recorded activations simultaneously from the entire left and right atrial endocardial surfaces. Twenty sustained (>40 s) atrial fibrillation episodes were induced by a train and premature stimuli protocol. Movies obtained immediately (Initiation stage) and 30 s (Early Stabilization stage) after premature stimulus were analyzed. Serial rotor formation was observed in all sustained inductions and none in nonsustained inductions. In sustained episodes maximal dominant frequency increased from (mean±SD) 11.5±1.74 Hz during Initiation to 14.79±1.30 Hz at Early Stabilization (P<0.0001) and stabilized thereafter. At rotor sites, mean cycle length (CL) during 10 prerotor activations increased every cycle by 0.53% (P=0.0303) during Initiation and 0.34% (P=0.0003) during Early Stabilization. In contrast, CLs at rotor sites showed abrupt decreases after the rotors appearances by a mean of 9.65% (P<0.0001) during both stages. At Initiation, atria-wide accelerations and decelerations during rotors showed a net acceleration result whereby post-rotors atria-wide minimal CL (CLmin) were 95.5±6.8% of the prerotor CLmin (P=0.0042). In contrast, during Early Stabilization, there was no net acceleration in CLmin during accelerating rotors (prerotor=84.9±11.0% versus postrotor=85.8±10.8% of Initiation, P=0.4029). Levels of rotor drift distance and velocity correlated with atria-wide acceleration. Nonrotor phase singularity points did not accelerate atria-wide activation but multiplied during Initiation until Early Stabilization. Increasing number of singularity points, indicating increased complexity, correlated with atria-wide CLmin reduction (P<0.0001). Conclusions Novel panoramic optical mapping of the atria demonstrates shortening CL at rotor sites during cholinergic atrial fibrillation onset. Atrial fibrillation acceleration toward Early Stabilization correlates with the net result of atria-wide accelerations during drifting rotors activity.

Cardiac magnetic resonance in recovering COVID-19 patients. Feature tracking and mapping analysis to detect persistent myocardial involvement.

BACKGROUND: Post-COVID-19 patients may incur myocardial involvement secondary to systemic inflammation. Our aim was to detect possible oedema/diffuse fibrosis using cardiac magnetic resonance imaging (CMR) mapping and to study myocardial deformation of the left ventricle (LV) using feature tracking (FT). METHODS: Prospective analysis of consecutively recruited post-COVID-19 patients undergoing CMR. T1 and T2 mapping sequences were acquired and FT analysis was performed using 2D steady-state free precession cine sequences. Statistical significance was set to p < 0.05. RESULTS: Included were 57 post-COVID-19 patients and 20 healthy controls, mean age 59 ± 15 years, men 80.7%. The most frequent risk factors were hypertension (33.3%) and dyslipidaemia (36.8%). The contact-to-CMR interval was 81 ± 27 days. LV ejection fraction (LVEF) was 61 ± 10%. Late gadolinium enhancement (LGE) was evident in 26.3% of patients (19.3%, non-ischaemic). T2 mapping values (suggestive of oedema) were higher in the study patients than in the controls (50.9 ± 4.3 ms vs 48 ± 1.9 ms, p < 0.01). No between-group differences were observed for native T1 nor for circumferential strain (CS) or radial strain (RS) values (18.6 ± 3.3% vs 19.2 ± 2.1% (p = 0.52) and 32.3 ± 8.1% vs 33.6 ± 7.1% (p = 0.9), respectively). A sub-group analysis for the contact-to-CMR interval (<8 weeks vs ≥ 8 weeks) showed that FT-CS (15.6 ± 2.2% vs 18.9 ± 2.6%, p < 0.01) and FT-RS (24.9 ± 5.8 vs 33.5 ± 7.2%, p < 0.01) values were lower for the shorter interval. CONCLUSIONS: Post-COVID-19 patients compared to heathy controls had raised T2 values (related to oedema), but similar native T1, FT-CS and FT-RS values. FT-CS and FT-RS values were lower in post-COVID-19 patients undergoing CMR after < 8 weeks compared to ≥ 8 weeks.

A scoring algorithm for the accurate differential diagnosis of regular wide QRS complex tachycardia.

BACKGROUND: The differential diagnosis of regular wide QRS complex tachycardia (RWQRST) remains the subject of numerous publications, all of which aim at diagnosis during the acute phase. Although an accurate diagnosis is necessary to make long-term decisions, it often leads to invasive testing. METHODS: Criteria with high positive predictive values (PPVs) for diagnosis can be obtained by analyzing the electrocardiogram (ECG) data during RWQRST and comparing them with these data at baseline. By assigning points to these criteria, a scoring algorithm to accurately diagnose numerous patients can be obtained. A total of 352 consecutive patients with RWQRST were included. Two electrophysiologists blind to patient condition analyzed the 16 criteria considered as having high PPVs. RESULTS: A total of 149 (42.3%) cases were supraventricular tachycardia (SVT), and 203 (57.7%) cases were ventricular tachycardia (VT). A higher percentage of patients with VT had structural heart disease (86.7% vs 16.1%). Seven of the 16 criteria analyzed had PPVs > 95%, and each criterion was assigned a score. A final score of -1 was indicative of SVT (PPV 98%); a score of 1 was indicative of VT (PPV 98%); and a score of ≥2 was indicative of VT (PPV 100%). A score of ≠0 was obtained for 51.7% of all cases of tachycardia, making it possible to reach a highly accurate diagnosis in approximately half of all cases. No cases of VT scored -1, and no cases of SVT scored ≥2. CONCLUSIONS: The current scoring system stands out for its high PPV (98%) and specificity (98%), enabling an accurate diagnosis for more than half of the patients.

Structural basis for the antiarrhythmic blockade of a potassium channel with a small molecule.

The acetylcholine-activated inward rectifier potassium current ( IKACh) is constitutively active in persistent atrial fibrillation (AF). We tested the hypothesis that the blocking of IKACh with the small molecule chloroquine terminates persistent AF. We used a sheep model of tachypacing-induced, persistent AF, molecular modeling, electrophysiology, and structural biology approaches. The 50% inhibition/inhibitory concentration of IKACh block with chloroquine, measured by patch clamp, was 1 µM. In optical mapping of sheep hearts with persistent AF, 1 µM chloroquine restored sinus rhythm. Molecular modeling suggested that chloroquine blocked the passage of a hydrated potassium ion through the intracellular domain of Kir3.1 (a molecular correlate of IKACh) by interacting with residues D260 and F255, in proximity to I228, Q227, and L299. 1H 15N heteronuclear single-quantum correlation of purified Kir3.1 intracellular domain confirmed the modeling results. F255, I228, Q227, and L299 underwent significant chemical-shift perturbations upon drug binding. We then crystallized and solved a 2.5 Å X-ray structure of Kir3.1 with F255A mutation. Modeling of chloroquine binding to the mutant channel suggested that the drug's binding to the pore becomes off centered, reducing its ability to block a hydrated potassium ion. Patch clamp validated the structural and modeling data, where the F255A and D260A mutations significantly reduced IKACh block by chloroquine. With the use of numerical and structural biology approaches, we elucidated the details of how a small molecule could block an ion channel and exert antiarrhythmic effects. Chloroquine binds the IKACh channel at a site formed by specific amino acids in the ion-permeation pathway, leading to decreased IKACh and the subsequent termination of AF.-Takemoto, Y., Slough, D. P., Meinke, G., Katnik, C., Graziano, Z. A., Chidipi, B., Reiser, M., Alhadidy, M. M., Ramirez, R., Salvador-Montañés, O., Ennis, S., Guerrero-Serna, G., Haburcak, M., Diehl, C., Cuevas, J., Jalife, J., Bohm, A., Lin,Y.-S., Noujaim, S. F. Structural basis for the antiarrhythmic blockade of a potassium channel with a small molecule.

Eplerenone Reduces Atrial Fibrillation Burden Without Preventing Atrial Electrical Remodeling.

BACKGROUND: The aldosterone inhibitor eplerenone (EPL) has been shown to reduce the incidence of atrial fibrillation (AF) in patients with systolic heart failure, but the mechanism is unknown. OBJECTIVES: This study hypothesized that by reducing atrial dilation and fibrosis in the absence of heart failure, EPL also reduces AF burden and prevents AF perpetuation. METHODS: The authors conducted a randomized controlled study in 34 sheep that were atrially tachypaced (13 ± 1 week). They compared daily oral EPL (n = 19) versus sugar pill (SP) treatment (n = 15) from the start of tachypacing. The endpoint was a continuous 7-day stretch of persistent AF (n = 29) or completion of 23 weeks tachypacing (n = 5). RESULTS: EPL significantly reduced the rate of left atrial dilation increase during AF progression. Atria from EPL-treated sheep had less smooth muscle actin protein, collagen-III expression, interstitial atrial fibrosis, and cell hypertrophy than SP-treated sheep atria did. However, EPL did not modify the AF-induced increase in the rate of dominant frequency and ion channel densities seen under SP treatment, but rather prolonged the time to persistent AF in 26% of animals. It also reduced the degree of fibrillatory conduction, AF inducibility, and AF burden. CONCLUSIONS: In the sheep model, EPL mitigates fibrosis and atrial dilation, modifies AF inducibility and AF complexity, and prolongs the transition to persistent AF in 26% of animals, but it does not prevent AF-induced electrical remodeling or AF persistence. The results highlight structural remodeling as a central upstream target to reduce AF burden, and the need to prevent electrical remodeling to avert AF perpetuation.

Safety threshold of R-wave amplitudes in patients with implantable cardioverter defibrillator.

OBJECTIVE: A safety threshold for baseline rhythm R-wave amplitudes during follow-up of implantable cardioverter defibrillators (ICD) has not been established. We aimed to analyse the amplitude distribution and undersensing rate during spontaneous episodes of ventricular fibrillation (VF), and define a safety amplitude threshold for baseline R-waves. METHODS: Data were obtained from an observational multicentre registry conducted at 48 centres in Spain. Baseline R-wave amplitudes and VF events were prospectively registered by remote monitoring. Signal processing algorithms were used to compare amplitudes of baseline R-waves with VF R-waves. All undersensed R-waves after the blanking period (120 ms) were manually marked. RESULTS: We studied 2507 patients from August 2011 to September 2014, which yielded 229 VF episodes (cycle length 189.6±29.1 ms) from 83 patients that were suitable for R-wave comparisons (follow-up 2.7±2.6 years). The majority (77.6%) of VF R-waves (n=13953) showed lower amplitudes than the reference baseline R-wave. The decrease in VF amplitude was progressively attenuated among subgroups of baseline R-wave amplitude (≥17; ≥12 to <17; ≥7 to <12; ≥2.2 to <7 mV) from the highest to the lowest: median deviations -51.2% to +22.4%, respectively (p=0.027). There were no significant differences in undersensing rates of VF R-waves among subgroups. Both the normalised histogram distribution and the undersensing risk function obtained from the ≥2.2 to <7 mV subgroup enabled the prediction that baseline R-wave amplitudes ≤2.5 mV (interquartile range: 2.3-2.8 mV) may lead to ≥25% of undersensed VF R-waves. CONCLUSIONS: Baseline R-wave amplitudes ≤2.5 mV during follow-up of patients with ICDs may lead to high risk of delayed detection of VF. TRIAL REGISTRATION NUMBER: NCT01561144; results.

Number of Beats in the Transition Zone With Fixed SA Interval during Right Ventricular Overdrive Pacing Determines Accessory Pathway Location in Orthodromic Reentrant Tachycardia.

BACKGROUND: Ventricular overdrive pacing (VOP) produces reset during the transition zone (TZ) of QRS fusion in orthodromic reentrant tachycardia (ORT) and after the TZ in atrioventricular nodal reentrant tachycardia (AVNRT), and this represents a simple diagnostic maneuver to differentiate the two tachycardia mechanisms. OBJECTIVE: The purpose of this study was to determine whether the number of beats with reset in the TZ predicts accessory pathway (AP) location in ORT. METHODS: We retrospectively reviewed 57 patients with ORT (21 left-sided AP, 20 septal AP, and 16 right-sided AP) and 20 patients with AVNRT (19 typical AVNRT and one atypical AVNRT) who underwent VOP from the right ventricular apex. We analyzed the number of beats with reset during or after the TZ, demonstrated by fixed ventricular stimulus-atrial (SA) interval during VOP. RESULTS: The overall mean tachycardia cycle length [CL] minus VOP CL was 22.6 ± 7.5 ms with no statistical difference between the groups (P = 0.480). The mean number of beats in the TZ with fixed SA interval was 2.5 ± 1.4 for the whole ORT group, 1.1 ± 0.4 for left-sided AP (range 1-2), 2.8  ±  0.9 for septal AP (range 1-5), and 4.0 ± 0.9 for right-sided AP (range 3-6) (P < 0.001). Using a cutoff >2 beats distinguished right- versus left-sided AP in all cases. CONCLUSION: Assessing the number of beats in the TZ with fixed SA interval during VOP helps to determine AP location in ORT and adds valuable information to an established simple diagnostic pacing maneuver, especially when a two-catheter simplified approach is employed.

[Electrical storm in patients with prophylactic defibrillator implantation]. / Evolución de los pacientes portadores de desfibrilador como prevención primaria tras un episodio de tormenta arrítmica.

INTRODUCTION: Little is known about the prevalence of electrical storm, baseline characteristics and mortality implications of patients with implantable cardioverter defibrillator in primary prevention versus those patients without electrical storm. We sought to assess the prevalence, baseline risk profile and survival significance of electrical storm in patients with implantable defibrillator for primary prevention. METHODS: Retrospective multicenter study performed in 15 Spanish hospitals. Consecutives patients referred for desfibrillator implantation, with or without left ventricular lead (at least those performed in 2010 and 2011), were included. RESULTS: Over all 1,174 patients, 34 (2,9%) presented an electrical storm, mainly due to ventricular tachycardia (82.4%). There were no significant baseline differences between groups, with similar punctuation in the mortality risk scores (SHOCKED, MADIT and FADES). A clear trigger was identified in 47% of the events. During the study period (38±21 months), long-term total mortality (58.8% versus 14.4%, p<0.001) and cardiac mortality (52.9% versus 8.6%, p<0.001) were both increased among electrical storm patients. Rate of inappropriate desfibrillator intervention was also higher (14.7 versus 8.6%, p<0.001). CONCLUSIONS: In the present study of patients with desfibrillator implantation for primary prevention, prevalence of electrical storm was 2.9%. There were no baseline differences in the cardiovascular risk profile versus those without electrical storm. However, all cause mortality and cardiovascular mortality was increased in these patients versus control desfibrillator patients without electrical storm, as was the rate of inappropriate desfibrillator intervention.

Spectral analysis-based risk score enables early prediction of mortality and cerebral performance in patients undergoing therapeutic hypothermia for ventricular fibrillation and comatose status.

BACKGROUND: Early prognosis in comatose survivors after cardiac arrest due to ventricular fibrillation (VF) is unreliable, especially in patients undergoing mild hypothermia. We aimed at developing a reliable risk-score to enable early prediction of cerebral performance and survival. METHODS: Sixty-one out of 239 consecutive patients undergoing mild hypothermia after cardiac arrest, with eventual return of spontaneous circulation (ROSC), and comatose status on admission fulfilled the inclusion criteria. Background clinical variables, VF time and frequency domain fundamental variables were considered. The primary and secondary outcomes were a favorable neurological performance (FNP) during hospitalization and survival to hospital discharge, respectively. The predictive model was developed in a retrospective cohort (n = 32; September 2006-September 2011, 48.5 ± 10.5 months of follow-up) and further validated in a prospective cohort (n = 29; October 2011-July 2013, 5 ± 1.8 months of follow-up). RESULTS: FNP was present in 16 (50.0%) and 21 patients (72.4%) in the retrospective and prospective cohorts, respectively. Seventeen (53.1%) and 21 patients (72.4%), respectively, survived to hospital discharge. Both outcomes were significantly associated (p < 0.001). Retrospective multivariate analysis provided a prediction model (sensitivity = 0.94, specificity = 1) that included spectral dominant frequency, derived power density and peak ratios between high and low frequency bands, and the number of shocks delivered before ROSC. Validation on the prospective cohort showed sensitivity = 0.88 and specificity = 0.91. A model-derived risk-score properly predicted 93% of FNP. Testing the model on follow-up showed a c-statistic ≥ 0.89. CONCLUSIONS: A spectral analysis-based model reliably correlates time-dependent VF spectral changes with acute cerebral injury in comatose survivors undergoing mild hypothermia after cardiac arrest.

Utility of intracardiac echocardiography for catheter ablation of complex cardiac arrhythmias in a medium-volume training center.

AIMS AND OBJECTIVES: New electrophysiology tools like intracardiac echocardiography (ICE) might help to minimize and early detect complications during cardiac ablation procedures. The aim of the study was to assess the utility and vascular safety of ICE during catheter ablation of complex cardiac arrhythmias in a medium-volume training center. METHODS: Prospective, observational study consisted of consecutive patients who underwent catheter-based ablation of complex cardiac arrhythmias. All procedures were performed using three-dimensional electro-anatomical mapping and routine cannulation of right and left femoral veins. The ICE probe was initially positioned at the mid-level of the right atrium and properly moved to monitor different steps of the procedure and identify complications. All procedure-related vascular complications were registered. RESULTS: One hundred two patients (age 61.4 ± 13.1 years, 69 male) underwent 110 ablation procedures. Pulmonary vein isolation was the most common ablation substrate (55.4%). Ventricular tachycardia (17.2%) and left atrial flutter procedures (16.4%) were also common. The use of ICE enabled us to early initiate anticoagulation and to optimize the transseptal puncture. It also provided the capability to early detect life-threatening complications such as tamponade (3.6%), along with important information during the procedure such as exact catheter location, lesion formation, and stability during radiofrequency delivery. Such benefits were not associated with a higher number of vascular complications. CONCLUSION: The use of ICE during catheter-based ablation of complex cardiac substrates provides technical features that may decrease complications and increase accuracy while applying radiofrequency, especially in training centers where fellows start to perform complex procedures.

Polyunsaturated Fatty acids in atrial fibrillation: looking for the proper candidates.

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice with growing prevalence in developed countries. Several medical and interventional therapies, such as atrial specific drugs and pulmonary vein isolation, have demonstrated prevention of recurrences. However, their suboptimal long-term success and significant rate of secondary effects have led to intensive research in the last decade focused on novel alternative and supplemental therapies. One such candidate is polyunsaturated fatty acids (PUFAs). Because of their biological properties, safety, simplicity, and relatively cheap cost, there is a special clinical interest in omega-3 PUFAs as a possible antiarrhythmic agent. Obtained from diets rich in fish, they represent one of the current supplemental therapies. At the cellular level, an increasing body of evidence has shown that n-3 PUFAs exert a variety of effects on cardiac ion channels, membrane dynamic properties, inflammatory cascade, and other targets related to AF prevention. In this article, we review the current basic and clinical evidence pertinent to n-3 PUFAs in AF treatment and prevention. We also discuss controversial outcomes among clinical studies and propose specific subsets of AF patients who will benefit most from n-3 PUFAs.