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Low estradiol status is associated with increased cardiovascular risk. We sought to determine the association between heart rate variability (HRV), a marker of cardiovascular risk, at baseline and in response to stressor as a function of menopausal status, menstrual cycle phase and estradiol level. Forty‐one healthy women (13 postmenopausal, 28 premenopausal) were studied. Eleven premenopausal women were additionally studied in the high and low estradiol phases of the menstrual cycle. HRV was calculated by spectral power analysis (low Frequency (LF), high frequency (HF) and LF:HF) at baseline and in response to graded Angiotensin II (AngII) infusion. The primary outcomes were differences in HRV at baseline and in response to AngII. Compared to premenopausal women in the low estradiol phase, postmenopausal women demonstrated lower baseline LF (p = 0.01) and HF (p < 0.001) measures, which were not significant after adjustment for age and BMI. In response to AngII, a decrease in cardioprotective HRV (ΔHF = −0.43 ± 0.46 ln ms2, p = 0.005 vs. baseline) was observed in postmenopausal women versus premenopausal women. Baseline HRV parameters did not differ by menstrual phase in premenopausal women. During the low estradiol phase, no differences were observed in the HRV response to AngII challenge. In contrast, women in the high estradiol phase were unable to maintain HRV (ΔLF = −0.07 ± 0.46 ln ms2, p = 0.048 response vs. baseline, ΔHF = −0.33 ± 0.74 ln ms2, p = 0.048 response vs. baseline). No association was observed between any measure of HRV and estradiol level. Menopausal status and the high estradiol phase in premenopausal women were associated with reduced HRV, a marker of cardiovascular risk. Understanding the role of estradiol in the modulation of cardiac autonomic tone may help guide risk reduction strategies in women. [ABSTRACT FROM AUTHOR]

Background: Characterization of left atrial (LA) hemodynamics in paroxysmal atrial fibrillation (PAF) may provide valuable insights for thromboembolic risk.Purpose: To evaluate LA vortex formation and velocity distributions by 4D flow MRI and identify associations with age, LA/LV (left ventricle) function, and established risk scores.Study Type: Prospective clinical.Population: Patients with PAF (n = 45, 46 ± 14 years) and healthy controls (n = 15, 54 ± 9 years) were enrolled.Mri Sequences: 3T standardized cardiac MRI protocol inclusive of 4D flow MRI.Assessment: Flow analysis planes were prescribed at each pulmonary vein. Velocity distribution analysis and vortex size quantification by the Lambda2 (λ2 ) method were performed in the LA.Statistics: Pearson or Spearman's correlation coefficients, r, were calculated to identify relationships between 4D flow-derived LA parameters and age, LA/LV function, and CHA2 DS2 -VASc stroke risk score. Univariate and multivariate determinants of stroke risk were assessed using linear regressions. To compare parameters within multiple groups, one-way analysis of variance or Kruskal-Wallis was used.Results: LA vortice sizes were observed in all subjects using λ2 showing inverse correlations with peak pulmonary vein inflow velocities (P < 0.05), and positive correlations with LA volume (P < 0.05). Vortex size was elevated in PAF at all phases of the cardiac cycle, being most prominent at end early diastole (3.98 ± 1.84 cm3 vs. 6.93 ± 3.11 cm3 , P = 0.001). Velocity distribution analysis showed a greater incidence of flow stasis among patients with PAF (P < 0.05). In univariate regression, vortex size was associated with the CHA2 DS2 -VASc risk score at peak systole (0.457 ± 0.038, P ≤ 0.001). However, in multivariate regression age was the dominant determinant of stroke risk (0.348 ± 0.012, P = 0.006).Data Conclusion: This study demonstrated that LA vortex size is increased among low-risk patients with PAF and is associated with the CHA2 DS2 -VASc risk score. Age remained the dominant determinant of stroke risk.Level Of Evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:871-884. [ABSTRACT FROM AUTHOR]

Importance of Line and Length for Mitral Isthmus Introduction Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. Methods and Results A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). Conclusions Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF. [ABSTRACT FROM AUTHOR]

Additional Criterion for Entrainment Introduction Entrainment criteria for the diagnosis of reentrant atrial tachycardia can be difficult to apply and cannot detect double-loop reentry. We sought to develop and clinically test a new criterion for the diagnosis of single- and double-loop reentry. Methods and Results (1) Proposed criterion: after sequential overdrive pacing at 2 different locations and assessing the first ensuing beats of tachycardia, the difference in activation time recorded between 2 appropriate stationary positions changes by 1 or 2 tachycardia cycle lengths; a change of 2 tachycardia cycle lengths usually indicates double-loop reentry rather than only a single-loop. (2) Clinical testing: multiple overdrive pacing maneuvers were undertaken and analyzed in 5 patients with common flutter (single-loop reentry). In total, 23 pairs of overdrive pacing maneuvers were performed using electrodes in the coronary sinus and a distribution of positions in the right atrium. In 22/23 pairs of maneuvers, the change in Activation Difference was within 2.6 ± 12.4 milliseconds of the tachycardia cycle length, confirming single loop reentry. For double-loop reentry, the literature was reviewed and 3 cases of double-loop reentry were identified with sufficient data. In all of these cases, double-loop reentry was detected and also the zone containing the common isthmus was identified. Conclusion The proposed criterion can diagnose single- and double-loop reentry atrial tachycardia using intracardiac recordings from any pair of well separated positions. The criterion does not require precise electrode placement or extensive activation mapping. [ABSTRACT FROM AUTHOR]

Partial Coronary Sinus Disconnection During Atrial Tachycardia. Introduction: Persistent atrial fibrillation (AF) ablation may lead to partial disconnection of the coronary sinus (CS). As a result, disparate activation sequences of the local CS versus contiguous left atrium (LA) may be observed during atrial tachycardia (AT). We aimed to evaluate the prevalence of this phenomenon and its impact on activation mapping. Methods: AT occurring after persistent AF ablation were investigated in 74 consecutive patients. Partial CS disconnection during AT was suspected when double potentials with disparate activation sequences were observed on the CS catheter. Endocardial mapping facing CS bipoles was performed to differentiate LA far-field from local CS potentials. Results: A total of 149 ATs were observed. Disparate LA-CS activations were apparent in 20 ATs after magnifying the recording scale (13%). The most common pattern (90%) was distal to proximal endocardial LA activation against proximal to distal CS activation, the latter involving the whole CS or its distal part. Perimitral macroreentry was more common when disparate LA-CS activations were observed (67% vs 29%; P = 0.002). Partial CS disconnection also resulted in 'pseudo' mitral isthmus (MI) block during LA appendage pacing in 20% of patients as local CS activation was proximal to distal despite distal to proximal activation of the contiguous LA. Conclusion: Careful analysis of CS recordings during AT following persistent AF ablation often reveals disparate patterns of activation. Recognizing when endocardial LA activation occurs in the opposite direction to the more obvious local CS signals is critical to avoid misleading interpretations during mapping of AT and evaluation of MI block. (J Cardiovasc Electrophysiol, Vol. 23, pp. 697-707, July 2012) [ABSTRACT FROM AUTHOR]

The approach to supraventricular tachycardia (SVT) diagnosis can be complex because it involves synthesizing baseline electrophysiologic features, features of the SVT, and the response(s) to pacing maneuvers. In this two-part review, we will mainly explore the latter while recognizing that neither of the former can be ignored, for they provide the context in which diagnostic pacing maneuvers must be correctly chosen and interpreted. Part 1 involved a detailed consideration of ventricular overdrive pacing, since this pacing maneuver provides the diagnosis in the majority of cases. In Part 2, other diagnostic pacing maneuvers that might be helpful when ventricular overdrive pacing is not diagnostic or appropriate, including attempts to reset SVT with single atrial or ventricular beats, para-Hisian pacing, apex versus base pacing, and atrial overdrive pacing, are discussed, as are some specific diagnostic SVT challenges encountered in the electrophysiology lab. There is considerable literature on this topic, and this review is by no means meant to be all-encompassing. Rather, we hope to clearly explain and illustrate the physiology, strengths, and weaknesses of what we consider to be the most important and commonly employed diagnostic pacing maneuvers, that is, those that trainees in cardiac electrophysiology should be well familiar with at a minimum.(PACE 2012; 35:757-769) [ABSTRACT FROM AUTHOR]

Role of CS Occlusion for Mitral Isthmus Ablation. Objective: To evaluate the safety and outcomes of mitral isthmus (MI) linear ablation with temporary spot occlusion of the coronary sinus (CS). Background: CS blood flow cools local tissue precluding transmurality and bidirectional block across MI lesion. Methods: In a randomized, controlled trial (CS-occlusion = 20, Control = 22), MI ablation was performed during continuous CS pacing to monitor the moment of block. CS was occluded at the ablation site using 1 cm spherical balloon, Swan-Ganz catheter with angiographic confirmation. Ablation was started at posterior mitral annulus and continued up to left inferior pulmonary vein (LIPV) ostium using an irrigated-tip catheter. If block was achieved, balloon was deflated and linear block confirmed. If not, additional ablation was performed epicardially (power ≤25 W). Ablation was abandoned after ∼30 minutes, if block was not achieved. Results: CS occlusion (mean duration −27 ± 9 minutes) was achieved in all cases. Complete MI block was achieved in 13/20 (65%) and 15/22 (68%) patients in the CS-occlusion and control arms, respectively, P = 0.76. Block was achieved with significantly small number (0.5 ± 0.8 vs 1.9 ± 1.1, P = 0.0008) and duration (1.2 ± 1.7 vs 4.2 ± 3.5 minutes, P = 0.009) of epicardial radiofrequency (RF) applications and significantly lower amount of epicardial energy (1.3 ± 2.4 vs 6.3 ± 5.7 kJ, P = 0.006) in the CS-occlusion versus control arm, respectively. There was no difference in total RF (22 ± 9 vs 23 ± 11 minutes, P = 0.76), procedural (36 ± 16 vs 39 ± 20 minutes, P = 0.57), and fluoroscopic (13 ± 7 vs 15 ± 10 minutes, P = 0.46) durations for MI ablation between the 2 arms. Clinically uneventful CS dissection occurred in 1 patient Conclusions: Temporary spot occlusion of CS is safe and significantly reduces the requirement of epicardial ablation to achieve MI block. It does not improve overall procedural success rate and procedural duration. Tissue cooling by CS blood flow is just one of the several challenges in MI ablation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 489-496, May 2012) [ABSTRACT FROM AUTHOR]

Electrophysiological Change and Mitral Line Block. Background: Achievement of complete conduction block across left mitral isthmus (MI) is a challenging endpoint of linear lesion, and recognizing the precise moment of block is important during ongoing ablation. The objective of this study is to evaluate the changes in P wave morphology and local MI potential at the moment of block during ongoing radiofrequency (RF) application. Methods and Results: We evaluated 69 patients (procedures) in whom successful MI linear conduction block was achieved during coronary sinus (CS) pacing. P wave morphology and/or local MI potential could be evaluated in 64 (93%) and 69 (100%) procedures, respectively. The achievement of MI block was associated with substantial instantaneous changes in 57/69 (82.6%) procedures. P wave morphology changed in 44 (64%) procedures with the change restricted to lateral leads in 39 (57%). Abrupt prolongation of local conduction delay from 106 ± 24 ms to 167 ± 39 ms (P < 0.0001) was observed on proximal bipole of ablation catheter in 34/69 (49.3%) procedures during ongoing RF application. In addition, prolongation of conduction delay was associated with significant change in the electrogram amplitude and polarity in 11 and 19 procedures, respectively. The substantial change in P wave morphology was not observed in any patients without achievement of complete block. Conclusions: The achievement of conduction block across MI line is associated with recognizable changes in the local MI electrograms and the P wave morphology especially in the lateral leads. These instantaneous critical changes may assist catheter ablation and indicate the requirement for prolonged RF application, if necessary. (J Cardiovasc Electrophysiol, Vol. pp. 1-7) [ABSTRACT FROM AUTHOR]

This two-part manuscript reviews diagnostic pacing maneuvers for supraventricular tachycardia (SVT). Part one will involve a detailed consideration of ventricular overdrive pacing (VOP), since this pacing maneuver provides the diagnosis in the majority of cases. This will include a review of the post-VOP response, fusion during entrainment, the importance of the VOP site, quantitative results of entrainment such as the postpacing interval, differential entrainment, and new criteria derived from features found at the beginning of the VOP train. There is a considerable literature on this topic, and this review is by no means meant to be all-encompassing. Rather, we hope to clearly explain and illustrate the physiology, strengths, and weaknesses of what we consider to be the most important and commonly employed diagnostic pacing maneuvers, that is, those that trainees in cardiac electrophysiology should be well familiar with at a minimum. (PACE 2011; 1-16) [ABSTRACT FROM AUTHOR]

Background Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle wasting disorder characterised by the absence of the protein dystrophin. Antisense oligonucleotides have been used to re-direct dystrophin pre-mRNA processing by blocking sequences crucial to pre-mRNA splicing, thereby inducing skipping of specific exons. We wished to determine which splicing motifs are most amenable as targets for antisense oligonucleotide induction of efficient and specific skipping of selected exons. Methods Antisense oligonucleotides were directed at regions of dystrophin exon 19 involved in pre-mRNA splicing, including the donor and acceptor splice sites and the exon splicing enhancer (ESE). Cultured myotubes were transfected with antisense oligonucleotides at various concentrations and studies undertaken to determine both specificity and efficiency of induced exon 19 skipping. Results Antisense oligonucleotides as small as 12 nucleotides targeting the ESE induced consistent and specific skipping of only exon 19 in both human and normal and mdx mouse myotubes. Antisense oligonucleotides directed at the donor and acceptor splice sites also induced specific exon 19 skipping while mismatched antisense oligonucleotides could only induce skipping when delivered at higher concentrations. No other dystrophin exons were removed from the mature mRNA as a consequence of these antisense oligonucleotides treatments. Conclusions Antisense oligonucleotides directed at the ESE tended to be marginally more efficient than those which targeted the donor or acceptor splice sites, based on their ability to induce specific skipping at lower concentrations. The specificity of exon removal does not appear to be a function of target selection, but may reflect the combination of the splicing motifs and position of that exon in the pre-mRNA. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents an evaluates the case of a 59 year old man with three previous ablations for symptomatic, drug-refractory persistent atrial fibrillation who presented to physicians for the ablation of incessant atrial tachycardia. A discussion of diagnostic testing and medical treatment which were performed on the patient is presented.

A case study of a 49 year old man with no known structural heart disease who presented to physicians with palpitations is presented. A discussion of diagnostic testing which was conducted on the patient, and resulted in him receiving a diagnosis of irregularly irregular supraventricular tachycardia, is presented.

Background Administrative data have limited sensitivity for case finding of atrial fibrillation/atrial flutter (AF/AFL). Linkage with clinical repositories of interpreted ECGs may enhance diagnostic yield of AF/AFL. Methods and Results We retrieved 369 ECGs from the institutional Marquette Universal System for Electrocardiography (MUSE) repository as validation samples, with rhythm coded as AF (n=49), AFL (n=50), or other competing rhythm diagnoses (n=270). With blinded, duplicate review of ECGs as the reference comparison, we compared multiple MUSE coding definitions for identifying AF/AFL. We tested the agreement between MUSE diagnosis and reference comparison, and calculated the sensitivity and specificity. Using a data set linking clinical registries, administrative data, and the MUSE repository (n=11 662), we assessed the incremental diagnostic yield of AF/AFL by incorporating ECG data to administrative data-based algorithms. The agreement between MUSE diagnosis and reference comparison depended on the coding definitions applied, with the Cohen κ ranging from 0.57 to 0.75. Sensitivity ranged from 60.6% to 79.1%, and specificity ranged from 93.2% to 98.0%. A coding definition with AF/AFL appearing in the first 3 ECG statements had the highest sensitivity (79.1%), with little loss of specificity (94.5%). Compared with the algorithms with only administrative data, incorporating ECG data increased the diagnostic yield of preexisting AF/AFL by 14.5% and incident AF/AFL by 7.5% to 16.1%. Conclusions Routine ECG interpretation using MUSE coding is highly specific and moderately sensitive for AF/AFL detection. Inclusion of MUSE ECG data in AF/AFL case identification algorithms can identify cases missed using administrative data-based algorithms alone.