Comprehensive Conduction System Pacing as Antiarrhythmic Strategy in Atrial Fibrillation

Abstract

Background

Elevated intracardiac filling pressures create a proarrhythmic environment that facilitates the development or progression of atrial fibrillation (AF). Accelerated lower rate pacing results in atrial decongestion by lowering intracardiac filling pressure and therefore may have an antiarrhythmic effect.

Case Summary

A 70-year-old woman with paroxysmal AF on flecainide progressed to symptomatic rate-controlled persistent AF 5 months ago. She underwent a dual-chamber pacemaker placement with an atrial lead to the Bachmann bundle area and a ventricular lead to the His bundle, and individualized accelerated resting heart rate pacing at 80 beats/min was implemented. She converted to sinus rhythm 18 days post-implant and has maintained sinus rhythm for 8 months, eliminating the need for atrioventricular node ablation.

Discussion

The “pace-and-wait” approach offers a primary antiarrhythmic treatment strategy for patients with paroxysmal or persistent AF by correcting interatrial conduction delay via Bachmann bundle pacing, correcting interventricular dyssynchrony via conduction system pacing, and optimizing cardiac hemodynamics by individualizing the lower rate limit. As such, the pace-and-wait approach can provide a treatment strategy that allows for sustained rhythm control and treatment of symptoms related to elevated intracardiac filling pressures, as well as offsets the side effects of pharmacologic rate control.

Take-Home Messages

The current era of pacemaker technology allows for the treatment of cardiac conditions beyond electrical impulse formation or conduction alone. In this report we highlight that comprehensive atrial and ventricular conduction system pacing along with accelerated pacing can provide atrial decongestion and atrial resynchronization for a patient with persistent AF.

Graphical Abstract

Current atrial fibrillation (AF) treatment strategies focus on rate or rhythm control alongside the management of associated risk factors such as hypertension, obesity, and sleep apnea. Rate control strategies are often limited by drug side effects (fatigue, hypotension, bradycardia), and symptoms can persist at times despite adequate rate control, likely owing to the irregular ventricular activation resulting in compromised cardiac efficiency.

Take-Home Messages

• •Combining Bachmann Bundle and ventricular conduction system pacing with accelerated lower rate pacing optimizes electrical and hemodynamic cardiac performance.
• •Atrial decongestion via accelerated lower rate pacing and atrial resynchronization via Bachmann Bundle pacing can provide rhythm control for a patient with persistent atrial fibrillation.

Rhythm control strategies via antiarrhythmic drugs or catheter ablation can be successful in alleviating symptoms, but have limited long-term effectiveness. The single-procedure success rates for paroxysmal AF are about 70% but closer to 50% for persistent AF and are further limited when severe left atrial enlargement is present.¹

Pacemaker implantation and atrioventricular (AV) node ablation is often reserved as a last resort when standard strategies fail, as patients will be rendered pacemaker dependent with a risk for pacemaker-induced ventricular dyssynchrony. The advantage of the pace-and-ablate strategy is that it provides definitive rate control and regularization of ventricular activation, eliminating the need for and side effects of pharmacologic therapy. Recently published data using increasingly physiologic approaches to ventricular pacing have led to a reappraisal, suggesting that earlier consideration of the pace-and-ablate strategy may be warranted. For example, the Ablate and Pace for Atrial Fibrillation–Cardiac Resynchronization Therapy (APAF-CRT) trial demonstrated that a pace-and-ablate strategy using biventricular pacing was superior to pharmacologic rate control in patients with permanent AF and heart failure.² Further support may hinge on the outcomes of currently ongoing trials evaluating the impact of conduction system pacing within the pace-and-ablate strategy, namely, the RAFT-P&A (Resynchronization in Patients With HF in AF Undergoing Pace & AVNA Strategy With LBBAP Compared With BiV Pacing; NCT05428787) and the PACE-FIB (Heart Rate Regularization in Atrial Fibrillation and Heart Failure; NCT05029570).

In contrast to the pace-and-ablate strategy, we describe a novel approach that combines accelerated lower rate pacing with atrial and ventricular conduction system pacing to exert a primary antiarrhythmic effect to obviate the need for AV node ablation—a strategy we call “pace-and-wait.” The conceptual basis for this supposition is twofold: 1) accelerated physiologic pacing benefits patients with normal left ventricular ejection fraction (LVEF) by lowering intracardiac filling pressure (ie, atrial decongestion) along with normalization of intracellular calcium cycling by lower rate regularization, and 2) implementing atrial pacing via the Bachmann bundle can correct interatrial conduction delay, improve AV conduction time, and improve AV synchrony. The electrical and hemodynamic benefits combine to reduce AF burden and, in some patients, restore sinus rhythm.

Clinical Vignette

A 70-year-old woman with polycythemia vera and symptomatic AF was referred for further management after antiarrhythmic therapy with flecainide (100 mg twice daily) and diltiazem (180 mg once daily) instituted 5 years earlier became ineffective. The progression from paroxysmal to persistent AF despite adequate rate control resulted in palpitations and debilitating shortness of breath, greatly limiting her previously active lifestyle, which included swimming, kayaking, walking, and caring for her disabled son. A 30-day cardiac monitor in November 2023 revealed a 100% AF burden with a controlled ventricular response at an average heart rate of 71 beats/min (range 50-148 beats/min). The last electrocardiogram in sinus rhythm, from September 2022, showed sinus bradycardia with a heart rate of 55 beats/min, a low P-wave amplitude, a PR interval of 188 ms, and a narrow QRS (Figure 1A).

Figure 1.

Baseline and Paced Electrical Characteristics and Baseline Echocardiogram

A 12-lead electrocardiogram at 25 mm/s sweep speed and 20 mm/mV gain during (A) sinus rhythm (P-wave duration 147 ms) and (B) atrial paced, ventricular sensed rhythm (P-wave duration 137 ms). (C) Fluoroscopic images of the permanent atrial and ventricular lead location in the right anterior oblique projection (top left) and the left anterior oblique projection (bottom left), as well as the sensed electrogram for the ventricular lead during implant with a local HV interval of 54 ms, QRS duration of 160 ms, with transient right bundle branch block and paced electrogram with Stimulus-to-V time of 36 ms, QRS duration of 110 ms with correction of transient right bundle branch block consistent with nonselective His bundle capture. (D) Apical 4-chamber view (transthoracic echocardiogram) illustrating significant left atrial enlargement and mitral valve inflow velocity with a calculated E/eʹ suggestive of diastolic dysfunction.

Transthoracic echocardiography performed in October 2023 demonstrated normal left ventricular systolic function (estimated ejection fraction 55%-60%), mild left ventricular hypertrophy with an elevated E/eʹ ratio, severe left atrial enlargement (left atrial volume index 57 mL/m²), and mild mitral regurgitation (Figure 1D).

Two treatment options were discussed with the patient: 1) AF catheter ablation, with a quoted single-procedure success rate of 50%, considering AF progression despite flecainide treatment and now 5 months of persistent AF as well as severe left atrial enlargement; 2) dual-chamber pacemaker placement with comprehensive conduction system pacing, combining atrial lead placement to the Bachmann bundle area and ventricular lead placement to the His-Purkinje system with accelerated resting heart rate programming, followed by interval cardioversion and, if necessary, subsequent AV node ablation. Considering the different wait times for the procedure and success rates, including the potential need for multiple ablation procedures, the patient opted for pacemaker implantation and, if needed, subsequent AV node ablation.

In February 2024, she underwent a dual-chamber pacemaker placement (Azure XT DR; Medtronic) with a lead to the His bundle (3830-69 delivered via a preshaped C315-His sheath; Medtronic) and a lead to the Bachmann bundle area (3830-59 delivered via a preshaped C315-S4 sheath; Medtronic). Because the patient was in AF, the Bachmann bundle lead placement was guided by fluoroscopy only. Right anterior oblique and left anterior oblique fluoroscopy views of the permanent lead placement, along with the 12-lead electrocardiogram with sensed His bundle electrogram and pacing from the permanent His bundle lead, are illustrated in Figure 1C.

The device was programmed AAIR (with automated mode switch to DDDR) and a lower rate limit of 80 beats/min; this rate limit was determined using a height-based and LVEF-modified algorithm (height 161 cm, LVEF 55%-60%).The paced and sensed AV delay was programmed to 150 ms with the goal to optimize AV hemodynamics. Additional device features, such as atrial preference pacing or atrial antitachycardia pacing, remained disabled to limit confounding of multiple therapeutic approaches. A daily dose of diltiazem 180 mg was continued for rate control of AF.

Subsequent remote follow-up demonstrated spontaneous termination of AF 18 days post-implant (Figures 2A and 2B). With atrial pacing, the paced P-wave (Figure 1B) was noted to be larger in amplitude and narrower than the native P-wave (Figure 1A) with a similar P-wave axis that is upright in limb leads II, III, and avF and biphasic in V1, consistent with our previously published criteria for successful Bachmann bundle pacing.³

Figure 2.

Pacemaker Follow-Up Data

(A) Device follow-up data for 8 months, from February 2024 to September 2024, and (B) a more detailed report of the first 3 weeks following device implantation. Note spontaneous conversion to sinus rhythm on day 18 post-implant and a gradual increase in device-detected physical activity to an average of 6 hours per day. AT/AF = atrial tachycardia/atrial fibrillation.

Over the subsequent 8 months of follow-up, AF burden remained low, at approximately 1.1%, and the patient exhibited a high level of device-detected daily activity, averaging 6 hours per day. In clinical follow-up, the patient described symptomatic improvement within 1 month of pacemaker placement. She reported improved energy levels with minimal shortness of breath, and, as such, she resumed walking her dog, working outdoors in her garden, and swimming. In this patient with persistent AF, severe left atrial enlargement, and preserved LVEF, these results underscore that a “Pace-and-Wait” strategy implementing accelerated comprehensive conduction system pacing can serve as a primary antiarrhythmic strategy.

Discussion

The pace-and-wait approach highlights a novel role for pacing as a primary antiarrhythmic treatment approach for patients with paroxysmal and persistent AF. Combining the electrophysiologic and hemodynamic benefits of accelerated pacing from atrial and ventricular conduction system leads provides symptom relief and increased physical activity levels. This AV node–sparing approach preserves the normal cardiac activation sequence while reserving the option of AV node ablation should AF eventually progress.

Pacemakers and AF: Contemporary Approach

The current paradigm for pacemakers in managing AF per se is that of a last resort when AV node ablation is considered. Traditional lead implantation in the right ventricular apex can lead to pacemaker-induced cardiomyopathy from interventricular and intraventricular dyssynchrony. The latter offsets the benefits of ventricular rate regularization following AV node ablation. On the atrial side, right atrial appendage pacing increases interatrial conduction time and is associated with an increased risk of AF. The advent of comprehensive atrial and ventricular conduction system pacing provides novel opportunities that have the potential to fundamentally change the pacing approach in patients with AF for 3 distinct but mutually reinforcing reasons (not all 3 will necessarily be present in every patient).

Correction of atrial conduction delay by Bachmann bundle pacing

Interatrial conduction delay, characterized by a prolonged P-wave duration, is associated with an increased AF risk that is proportional to the degree of conduction delay. Electrically guided Bachmann bundle pacing can correct atrial dyssynchrony, reducing the risk of new-onset AF and AF burden in patients with preexisting paroxysmal AF.⁴ In a computational model, Bachmann bundle pacing has been shown to lower left atrial filling pressures by optimizing the timing between left atrial and left ventricular mechanical function compared with right atrial septal pacing or right atrial appendage pacing.⁵

Correction of interventricular conduction delay by conduction system pacing

Dyssynchronous ventricular activation, whether due to His-Purkinje disease or dyssynchronous ventricular pacing, increases left ventricular and left atrial filling pressures, which is proarrhythmic.⁶ Overcoming interventricular conduction delay with ventricular conduction system pacing has been shown to reduce AF burden.⁷ Furthermore, the extent to which dromotropic abnormalities contribute to inefficient ventricular filling, especially as heart rate accelerates with activity, can now be corrected with optimized AV interval programming without the cost of dyssynchronous ventricular activation from right ventricular apical pacing.

Filling pressure reduction by accelerated lower rate pacing

In patients with preserved LVEF, heart rate suppression raises intracardiac filling pressures, which in turn increases the risk for AF and heart failure.^8,9 In patients with an underlying sinus rhythm, atrial pacing rates of up to 125 beats/min have been consistently shown to decrease left atrial and left ventricular filling pressures in patients with an LVEF of ≥50%.^10,11 Additionally, accelerated resting heart rate pacing has been shown to improve quality of life, physical activity, and natriuretic peptide levels in patients with heart failure with preserved ejection fraction, a common comorbidity of AF.^12,13 Conceptually, ventricular conduction system pacing in patients with persistent AF and controlled ventricular response rate should achieve lower intracardiac filling pressures by accelerating, regularizing, and possibly resynchronizing ventricular activity. Lowering left ventricular filling pressures will also reduce left atrial filling pressures and provide antiarrhythmic effects, as evident in this patient.

Clinical Perspective

Cardiac pacing as a treatment for AF and heart failure with preserved ejection fraction is an emerging area of investigation. Here, we provide the first evidence to our knowledge that a mechanistically guided and physiologically implemented pacing strategy has the potential to shift the use of pacing in AF toward optimizing hemodynamics and cardiac conduction, with the goal of restoring sinus rhythm. The impact of accelerated comprehensive conduction system pacing on AF will require a thorough evaluation in clinical trials.

Funding Support and Author Disclosures

Drs Habel, Lustgarten, and Meyer have received research funding from Medtronic. Dr Meyer has reported grants from the Engdahl Family Foundation. Dr Meyer and the University of Vermont have licensed patents for the use of pacemakers for the prevention and treatment of atrial fibrillation and heart failure with preserved ejection fraction. Mr Kabir has reported that he has no relationships relevant to the contents of this paper to disclose.