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ImportancePatients with heart failure with preserved ejection fraction (HFpEF) with a pacemaker may benefit from a higher, more physiologic backup heart rate than the nominal 60 beats per minute (bpm) setting.ObjectiveTo assess the effects of a moderately accelerated personalized backup heart rate compared with 60 bpm (usual care) in patients with preexisting pacemaker systems that limit pacemaker-mediated dyssynchrony.Design, Setting, and ParticipantsThis blinded randomized clinical trial enrolled patients with stage B and C HFpEF from the University of Vermont Medical Center pacemaker clinic between June 2019 and November 2020. Analysis was modified intention to treat.InterventionsParticipants were randomly assigned to personalized accelerated pacing or usual care and were followed up for 1 year. The personalized accelerated pacing heart rate was calculated using a resting heart rate algorithm based on height and modified by ejection fraction.Main Outcomes and MeasuresThe primary outcome was the serial change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score. Secondary end points were changes in N-terminal pro–brain natriuretic peptide (NT-proBNP) levels, pacemaker-detected physical activity, atrial fibrillation from baseline, and adverse clinical events.ResultsOverall, 107 participants were randomly assigned to the personalized accelerated pacing (n = 50) or usual care (n = 57) groups. The median (IQR) age was 75 (69-81) years, and 48 (48%) were female. Over 1-year follow-up, the median (IQR) pacemaker-detected heart rate was 75 (75-80) bpm in the personalized accelerated pacing arm and 65 (63-68) bpm in usual care. MLHFQ scores improved in the personalized accelerated pacing group (median [IQR] baseline MLHFQ score, 26 [8-45]; at 1 month, 15 [2-25]; at 1 year, 9 [4-21]; P P = .03). In addition, personalized accelerated pacing led to improved changes in NT-proBNP levels (mean [SD] decrease of 109 [498] pg/dL vs increase of 128 [537] pg/dL with usual care; P = .02), activity levels (mean [SD], +47 [67] minutes per day vs −22 [35] minutes per day with usual care; P P = .04) over 1-year of follow-up. Adverse clinical events occurred in 4 patients in the personalized accelerated pacing group and 11 patients in usual care.Conclusions and RelevanceIn this study, among patients with HFpEF and pacemakers, treatment with a moderately accelerated, personalized pacing rate was safe and improved quality of life, NT-proBNP levels, physical activity, and atrial fibrillation compared with the usual 60 bpm setting.Trial RegistrationClinicalTrials.gov Identifier: NCT04721314

Aims Evaluate whether Bachmann’s bundle pacing (BBp) defined by electrocardiographic (ECG) criteria is associated with less atrial fibrillation/tachycardia (AF/AT) compared with anatomically defined right atrial septal pacing (RASp) and right atrial appendage pacing (RAAp). Methods and results This is a retrospective study comparing BBp with non-specific RASp and RAAp on new incidence, burden, and recurrence of AF/AT. We included patients who underwent atrial lead placement between 2006 and 2019 and received > 20% atrial pacing. BBp was defined by paced P-wave morphology and fluoroscopic lead position. Compared with RASp (n = 107) and RAAp (n = 108), AF/AT burden was lower in the BBp (n = 134) group by repeated measures ANOVA (P < 0.001). Over 2-year follow-up, AF/AT burden increased in the RASp (P < 0.01) and RAAp (P < 0.01) groups but did not significantly change in the BBp group (P = 0.91). Atrial arrhythmia burden was lower in the BBp group than the RASp and RAAp groups at 12–15, 18–21, and 24–27 months (P < 0.05) after pacemaker placement. Risk of AF/AT recurrence was lower in BBp than RASp (HR 0.43; P < 0.01) and RAAp patients (HR 0.29, P < 0.01). Risk of de novo AF/AT was also lower in BBp than in RASp (OR 0.12; P < 0.01) and RAAp patients (OR 0.20, P < 0.01). Conclusion Bachmann’s bundle pacing defined using P-wave criteria was associated with decreased atrial arrhythmia burden, recurrence, and de novo incidence compared with right atrial septal pacing and right atrial appendage pacing.

Background Lower heart rates (HRs) prolong diastole, thereby raising filling pressures and wall stress (1,2), slowing myocardial relaxation (3), and increasing central blood pressure via superposition of reflected peripheral pressure waves onto systole (2,4). As a result, lower HRs may be associated with higher brain natriuretic peptide (BNP) levels and incident atrial fibrillation (AF). Beta-blockers (BBs) may thereby increase the risk for AF. Purpose Examine the relationships of HR, BNP, BB use and new-onset AF in the REVEAL-AF and SPRINT cohort of subjects at risk for developing AF. Methods In REVEAL-AF, 383 subjects (52% male, mean age 71.5±9.8 years) without a history of AF and a mean CHA2DS2VASC score of 4.4±1.3 received an insertable cardiac monitor and were followed up to 30 months. Baseline HRs were averaged between 8AM and 8PM for the first week post-implantation. Adjudicated AF lasting ≥6 minutes was defined as new-onset AF. In SPRINT, 7595 patients (64% male, mean age 67.5±9.2 years) without prior history of AF and a mean CHA2DS2VASC score of 2.3±1.2 were followed for up to 60 months. Baseline average HR was derived from three seated measurements taken at the initial clinical visit. 12-lead ECG at baseline, 2 years, 4 years and close-out visit were used to determine presence of AF. Based on longitudinal medication inventories BB use was categorized into “on BB” vs “never on BB” for the duration of the trial. Results The median daytime HR in the REVEAL-AF cohort was 75bpm [interquartile range, IQR 68–83]. Subjects with below median HRs had 2.4-fold higher BNP levels when compared to subjects with above median HRs (median BNP [IQR]: 62pg/dl [37–112] vs. 26pg/dl [13–53], p Conclusion Lower HRs and BB use are associated with higher BNP levels and incident AF, supporting the hypothesis that lower HRs mimic and/or exacerbate the hemodynamic effects of diastolic dysfunction and promote atrial myopathy. The effects of BBs on clinical outcomes in patient populations outside the context of heart failure with reduced ejection fraction will need to be reassessed. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health

Author(s): Infeld, Margaret; Avram, Robert; Wahlberg, Kramer; Silverman, Daniel N; Habel, Nicole; Lustgarten, Daniel L; Pletcher, Mark J; Olgin, Jeffrey E; Marcus, Gregory M; Meyer, Markus

His bundle pacing has the advantage of restoring physiologic ventricular activation, rather than mimicking it as is the case with biventricular pacing. Engaging intact His-Purkinje fibers distal to conduction disease reestablishes multisite simultaneous endo-to-epicardial activation, resulting in normal torsional contraction and optimal cardiac output.

His bundle pacing has the advantage of restoring physiologic ventricular activation, rather than mimicking it as is the case with biventricular pacing. Engaging intact His-Purkinje fibers distal to conduction disease reestablishes multisite simultaneous endo-to-epicardial activation, resulting in normal torsional contraction and optimal cardiac output.

His bundle pacing has the advantage of restoring physiologic ventricular activation, rather than mimicking it as is the case with biventricular pacing. Engaging intact His-Purkinje fibers distal to conduction disease reestablishes multisite simultaneous endo-to-epicardial activation, resulting in normal torsional contraction and optimal cardiac output.

Cardiac resynchronization therapy (CRT) by the way of biventricular (BiV) pacing is an established component of heart failure treatment in selected patients and aims at reestablishing synchrony between right ventricular and left ventricular activation [1]. However, this form of cardiac excitation fails to emulate the multisite simultaneous endo- to epicardial activation resulting in torsional contraction, which is critical to achieve optimal cardiac output.

Dynamic left ventricular outflow tract obstruction (LVOTO) due to systolic anterior motion (SAM) of the mitral valve (MV) has been described in a small subset of patients with stress cardiomyopathy (SCM). However, encountering LVOTO, severe MV regurgitation and cardiogenic shock in SCM is

Aims A key mechanism responsible for atrial fibrillation is multi-wavelet reentry (MWR). We have previously demonstrated that ablation in regions of increased circuit density reduces the duration of, and decreases the inducibility of MWR. In this study, we demonstrate a method for identifying local circuit density using electrogram frequency and validated its effectiveness for map-guided ablation in a computer model of MWR. Methods and results We simulated MWR in tissues with variation of action potential duration and intercellular resistance. Electrograms were calculated using various electrode sizes and configurations. We measured and compared the number of circuits to the tissue activation frequency and electrogram frequency using three recording configurations [unipolar, contact bipolar, orthogonal closed unipolar (OCU)] and two frequency measurements (dominant frequency, centroid frequency). We then used the highest resolution electrogram frequency map (OCU centroid frequency) to guide the placement of lesions to high frequency regions. Map-guided ablation was compared with no ablation and random/blind ablation lesions of equal length. Electrogram frequency correlated with tissue frequency and circuit density as a function of electrode spatial resolution. Map-guided ablation resulted in a significant reduction in MWR duration (142 ± 174 vs. 41 ± 63 s). Conclusion Electrogram frequency correlates with circuit density in MWR provided electrodes have high spatial resolution. Map-guided ablation is superior to no ablation and to blind/random ablation.

In this article we will review differential diagnostic pacing maneuvers. It is not meant to be an exhaustive review of all such maneuvers. Rather, we offer some general analytic principles as they apply to electrophysiology (EP) and illustrate their use through several examples. Our hope is to provide a framework for thinking about electrogram data that acts more like a compass and map than like a specific set of directions. Amongst the most helpful pieces of advice that we can offer the EP trainee is to actively try to picture the waves of electricity spreading through the heart, passing beneath the recording electrodes and generating the electrograms you seek to interpret. Digest the fact that more than one propagation pattern can result in the same electrogram pattern and that differential diagnostic pacing is aimed at distinguishing between these possibilities. A fundamental tenet of differential diagnostic maneuvers of any kind (not simply pacing) is to choose a test that maximizes the difference between possible explanations. This perspective and a careful and meticulous cataloguing of what you can unambiguously conclude from the electrograms versus what remains to be determined via pacing offers the best approach to succeeding at EP. We will discuss pacing maneuvers in three contexts: differential diagnosis of narrow complex tachycardia, mapping of accessory pathways, and Para-Hisian pacing.

Aims Catheter ablation strategies for treatment of cardiac arrhythmias are quite successful when targeting spatially constrained substrates. Complex, dynamic, and spatially varying substrates, however, pose a significant challenge for ablation, which delivers spatially fixed lesions. We describe tissue excitation using concepts of surface topology which provides a framework for addressing this challenge. The aim of this study was to test the efficacy of mechanism-based ablation strategies in the setting of complex dynamic substrates. Methods and results We used a computational model of propagation through electrically excitable tissue to test the effects of ablation on excitation patterns of progressively greater complexity, from fixed rotors to multi-wavelet re-entry. Our results indicate that (i) focal ablation at a spiral-wave core does not result in termination; (ii) termination requires linear lesions from the tissue edge to the spiral-wave core; (iii) meandering spiral-waves terminate upon collision with a boundary (linear lesion or tissue edge); (iv) the probability of terminating multi-wavelet re-entry is proportional to the ratio of total boundary length to tissue area; (v) the efficacy of linear lesions varies directly with the regional density of spiral-waves. Conclusion We establish a theoretical framework for re-entrant arrhythmias that explains the requirements for their successful treatment. We demonstrate the inadequacy of focal ablation for spatially fixed spiral-waves. Mechanistically guided principles for ablating multi-wavelet re-entry are provided. The potential to capitalize upon regional heterogeneity of spiral-wave density for improved ablation efficacy is described.

The goal of this study was to determine quantitative relationships between electrophysiologic parameters and the propensity of cardiac tissue to undergo atrial fibrillation. We used a computational model to simulate episodes of fibrillation, which we then characterized in terms of both their duration and the population dynamics of the electrical waves which drove them. Monte Carlo sampling revealed that episode durations followed an exponential decay distribution and wave population sizes followed a normal distribution. Half-lives of reentrant episodes increased exponentially with either increasing tissue area to boundary length ratio (A/BL) or decreasing action potential duration (APD), resistance (R) or capacitance (C). We found that the qualitative form of fibrillatory activity (e.g., multi-wavelet reentry (MWR) vs. rotors) was dependent on the ratio of resistance and capacitance to APD; MWR was reliably produced below a ratio of 0.18. We found that a composite of these electrophysiologic parameters, which we term the fibrillogenicity index (Fb = A/(BL*APD*R*C)), reliably predicted the duration of MWR episodes (r2 = 0.93). Given that some of the quantities comprising Fb are amenable to manipulation (via either pharmacologic treatment or catheter ablation), these findings provide a theoretical basis for the development of titrated therapies of atrial fibrillation.

In this article we will review differential diagnostic pacing maneuvers. It is not meant to be an exhaustive review of all such maneuvers. Rather, we offer some general analytic principles as they apply to electrophysiology (EP) and illustrate their use through several examples. Our hope is to provide a framework for thinking about electrogram data that acts more like a compass and map than like a specific set of directions. Amongst the most helpful pieces of advice that we can offer the EP trainee is to actively try to picture the waves of electricity spreading through the heart, passing beneath the recording electrodes and generating the electrograms you seek to interpret. Digest the fact that more than one propagation pattern can result in the same electrogram pattern and that differential diagnostic pacing is aimed at distinguishing between these possibilities. A fundamental tenet of differential diagnostic maneuvers of any kind (not simply pacing) is to choose a test that maximizes the difference between possible explanations. This perspective and a careful and meticulous cataloguing of what you can unambiguously conclude from the electrograms versus what remains to be determined via pacing offers the best approach to succeeding at EP. We will discuss pacing maneuvers in three contexts: differential diagnosis of narrow complex tachycardia, mapping of accessory pathways, and Para-Hisian pacing.

Background— A key mechanism responsible for atrial fibrillation is multiwavelet re-entry (MWR). We have previously demonstrated improved efficiency of ablation when lesions were placed in regions of high circuit-density. In this study, we undertook a quantitative assessment of the relative effect of ablation on the probability of MWR termination and the inducibility of MWR, as a function of lesion length and circuit-density overlap. Methods and Results— We used a computational model to simulate MWR in tissues with (and without) localized regions of decreased action potential duration and increased intercellular resistance. We measured baseline circuit-density and distribution. We then assessed the effect of various ablation lesion sets on the inducibility and duration of MWR as a function of ablation lesion length and overlap with circuit-density. Higher circuit-density reproducibly localized to regions of shorter wavelength. Ablation lines with high circuit-density overlap showed maximum decreases in duration of MWR at lengths equal to the distance from the tissue boundary to the far side of the high circuit-density region (high-overlap, −43.5% [confidence interval, −22.0% to −65.1%] versus low-overlap, −4.4% [confidence interval, 7.3% to −16.0%]). Further ablation (beyond the length required to cross the high circuit-density region) provided minimal further reductions in duration and increased inducibility. Conclusions— Ablation at sites of high circuit-density most efficiently decreased re-entrant duration while minimally increasing inducibility. Ablation lines delivered at sites of low circuit-density minimally decreased duration yet increased inducibility of MWR.

To improve spatial resolution in recordings of intra-cardiac electrograms we characterized the utility of a novel configuration of two recording electrodes arranged perpendicularly to the endocardial surface. We hypothesized that this configuration denoted as orthogonal close unipolar (OCU) would combine advantages of conventional unipolar and contact bipolar (CBP) configurations. Electrical excitation was simulated in a computational model as arising from dipole current or from multi-wavelet reentry sources. Recordings were calculated for electrode tips 1 mm above the plane of the heart. Analogous recordings were obtained from swine hearts. Electrograms recorded with CBP showed strong dependence on orientation of the electrode pair with respect to the direction of spread of tissue excitation. By contrast, OCU recordings exhibited no directional dependence. OCU was significantly superior to CBP with respect to avoidance of far-field confounding of local tissue activity; the average far-field/near-field ratios for CBP and OCU were 0.09 and 0.05, respectively, for the simulated dipole current sources. In the swine hearts the ratios of ventricular to atrial signals for CBP and OCU were 0.15 ± 0.07 and 0.08 ± 0.09, respectively (p < 0.001). The difference between the actual dominant frequency in the tissue and that recorded by the electrodes was 0.44 ± 0.33 Hz for OCU, 0.58 ± 0.40 Hz for unipolar, and 0.62 ± 0.46 Hz for CBP. OCU confers improved spatial resolution compared with both unipolar and CBP electrode configurations. Unlike the case with CBP, OCU recordings are independent of excitation wave-front direction.

We will lookat 4 specific insights—new, emerging, and largely unpub-lished—from4teamsoftheAorticInstituteatYale:clinical,surgical pathology, engineering, and molecular genetics.CLINICAL: CAN THE AORTIC WALLCOMMUNICATE WITH US?It is well known that most patients with thoracic aorticaneurysms (as many as 95%

Background Electrogram fractionation can result when multiple groups of cardiac cells are excited asynchronously within the recording region of a mapping electrode. The spatial resolution of an electrode thus plays an important role in mapping complex rhythms. Methods We used a computational model, validated against experimental measurements in vitro, to determine how spatial resolution is affected by electrode diameter, electrode length, interelectrode distance (in the case of bipolar recordings), and height of the electrode above a dipole current source. Results We found that increases in all these quantities caused progressive degradation in two independent measures of spatial resolution, with the strongest effect being due to changes in height above the tissue. Conclusion Our calculations suggest that if electrodes could be constructed to have negligible dimensions compared with those in use today, we would increase resolution by about one order of magnitude at most.

Ablation of atrial autonomic inputs exerts antifibrillatory effects. However, because ablation destroys both myocardium and nerve cells, the effect of autonomic withdrawal alone remains unclear. We therefore examined the effects of pharmacologic autonomic blockade (PAB) on frequency and fractionation in patients with atrial fibrillation (AF).Esmolol and atropine were administered and electrograms were recorded simultaneously from both atria and the coronary sinus. In 17 patients, AF was recorded for 5 minutes and dominant frequency (DF) and continuous activity (CA) were compared before and during PAB.Examination of the pooled data (537 sites, 17 patients) revealed a statistically significant decrease in mean DF (5.61–5.43Hz, P0.001) during PAB. Site-by-site analysis showed that 67% of sites slowed (0.45 ± 0.59 Hz), whereas 32% accelerated (0.49 ± 0.59Hz). Fractionation was reduced: median CA decreased from 31% to 26% (P0.001). In patient-by-patient analysis, mean DF/median CA decreased in 13 of 17 patients and increased in four. The spatial heterogeneity of DF decreased in nine of 17 patients (spatial coefficient of variation of DF at "nondriver sites" decreased by a mean of 2%).PAB decreases DF and CA in the majority of sites. Given the complexity of interactions between atrial cells during AF, the effects of PAB on DF and fractionation are more heterogeneous than the effects of PAB on isolated cells.

We have developed a straightforward, physiologically based mathematical in silico model of cardiac electric activity to facilitate understanding of the fundamental principles that determine how excitation propagates through the heart. Despite its simplicity, the model provides a very powerful teaching tool. In fact, its simplicity is integral to the model's utility. The contrast between the minimal set of rules that govern the model's function and the widely varied complex behaviors it can manifest offers insight into the nature of emergent behavior in wave propagation. Emergence in this context refers to the richness of the tissue activation patterns that arise from the aggregate behavior of the simple cells that comprise the tissue. Each cell can be active, inactive, or refractory and interacts only with its immediate neighbors. From these simple building blocks, very elaborate global behaviors emerge. From the perspective of the electrophysiology student, the notion of emergent properties can act as a Rosetta stone for deciphering electrophysiological behavior. The spread of electric excitation through the intricate 3D structure of the heart can take widely varied forms, ranging from the orderly propagation seen during sinus rhythm to the marked disorganization seen during ventricular fibrillation. Observation of the diverse and sometimes complex patterns of conduction (eg, unidirectional block, reentry, spiral waves) as well as the responses to pacing maneuvers (eg, entrainment) suggests to the electrophysiology student a nearly infinite array of possibilities, the mastery of which can be daunting. However, with study, it becomes apparent that one need not memorize every possible cardiac behavior. Instead, there are overarching principles of cardiac excitation and propagation1 from which these varied phenomena emerge and through which one can understand and predict rather than memorize electrophysiological behavior. Understanding these fundamental principles is integral to mastering electrophysiology. A framework for interpreting clinical observations predicated on these …

BACKGROUND It has been proposed that sequential mapping of dominant frequency (DF) and complex fractionated atrial electrograms (CFAE) can identify target sites for ablation of atrial fibrillation (AF). These mapping strategies are valid only if DF and CFAE are temporally stable on the timescale of the mapping procedure. We postulate that DF and CFAE are temporally variable; consequently, sequential mapping can be misleading. OBJECTIVE To make prolonged spatially stable multielectrode recordings to assess the temporal stability of DF and CFAE. METHODS We recorded electrical activity for 5 minutes with the use of a 64-electrode basket catheter placed in the left atrium of 18 patients presenting for AF ablation. DF and CFAE were determined off-line, and their temporal variability was quantified. Maps created from simultaneous versus sequentially acquired data were compared. RESULTS DF was temporally variable: the average temporal coefficient of variation was 22.7% 5.4%. DF sites were transient, meeting criteria for only 22.1 seconds out of 5 minutes. Similarly, CFAEs were transient (average duration of CFAE 8.8 11.3 seconds). DF and CFAE sequential maps failed to identify 93.0% 12.4% and 35.9% 14.9% of DF and CFAE sites, respectively. CONCLUSION Because of temporal variability, sequential DF and CFAE maps do not accurately reflect the spatial distribution of excitation frequency during any given sampling interval. The spatial distribution of DF and CFAE sites on maps created with sequential point acquisition depends upon the time at which each site is sampled.