Exertional Intolerance After a Leadless Pacemaker Implant: What Is the Mechanism?

An 81-year-old man with a history of hypertension, coronary artery disease, lung cancer status post lobectomy, paroxysmal atrial fibrillation status post ablation, severe aortic stenosis status post transaortic valve replacement (TAVR) complicated by complete heart block who had a Medtronic Micra AV (model MC1AVR1) leadless pacemaker (LP) implanted. About a year prior to TAVR, he had been feeling dyspnea, fatigue, and lightheadedness. His symptoms did not improve after TAVR, and his exercise tolerance became limited despite being physically active. He had an ECG exercise stress test during which he developed a wide-complex rhythm that correlated with his symptoms (Figure 1, top panel); so, he was referred for further evaluation. His pacemaker interrogation showed that he was ventricularly paced only 3.8% of the time (Figure 1, bottom panel) while set at VDD 50. What is the cause of this patient's symptoms? The ECG tracing during exercise in the top panel clearly shows a transition from a sinus rhythm with preserved atrioventricular (AV) nodal conduction with right bundle branch block at ∼75 bpm to ventricular pacing. This patient has intact AV conduction (shown in the beginning of the tracing) that apparently recovered after his TAVR procedure. However, initiation of asynchronous ventricular pacing initially leads to some fusion complexes followed by ventricular paced beats. The inferior axis of the paced complexes reflects the superior position of the Micra LP that had been implanted at the basal right ventricular septum. The observed ventricular pacing is not from tracking in VDD mode and this becomes more apparent at the end of the tracing where there appears to be no clear relationship between the P waves and the paced ventricular complexes. Review of this patient's device diagnostics (bottom panel) reveals a leftward shift of his heart rate histograms with heart rates predominantly <80 bpm and 3.8% ventricular pacing (1.8% AM–VP and 2.0% VP only). This patient's intact AV conduction is reflected by the high proportion of “AV Conduction Mode Switch” (91.4%) and VS only (92.8%). This AV Conduction Mode Switch feature, which is nominally programmed ON in the Micra AV LP, periodically switches VDD to VVI+ mode at the programmed AV Conduction Mode Switch Lower Rate (40 bpm with Micra AV; programmable with Micra AV2, ranging 40–70, nominally 50 bpm) to limit the amount of RV pacing and maximize device longevity by disabling atrial sensing during mode switch. If the intrinsic rate is above the programmable AV Conduction Mode Switch Lower Rate, the device remains in VVI+ mode; if the intrinsic rate drops below the AV Conduction Mode Switch Lower rate (2 of 4 beats are ventricular pacing), the device switches back to VDD mode [1]. However, in the setting of intact AV conduction and a ventricular rate above the AV Conduction Mode Switch Lower rate, what is the reason for the ventricular pacing, that was causing significant symptoms in this patient? The Micra “Activity Mode Switch” feature switches the device to a rate-responsive mode (VDIR) when it detects high activity and a low ventricular rate [1]. This feature was designed to provide better AV synchrony during activity when the atrial activity is more difficult to track due to patient movement as well as fusion of accelerometer signals related to atrial contraction (A4) and the early period of ventricular filling (A3). If the accelerometer-based sensor rate is at the patient's activities of daily living (ADL) rate or higher and the target pacing rate is significantly higher than the current ventricular rate, the device will switch to VDIR and provide pacing at the rate response rate. When activity ceases, and the sensor rate decreases to below the programmed ADL rate, the Micra AV LP switches back to VDD mode. This patient's symptoms were reproduced when he started to ventricularly pace during minimal activity in the office, and this was confirmed with simultaneous device interrogation. His Micra AV LP was reprogrammed from VDD to VVI, and during repeat exercise, his symptoms of light-headedness from pacemaker syndrome abated when he no longer ventricularly paced. Pacemaker syndrome is caused by ventricular pacing and loss of AV synchrony or retrograde VA conduction that results in hemodynamic, neurohumoral, and baroreceptor changes [2]. Symptoms are variable in quality and severity, and they include fatigue, palpitations, chest discomfort, dyspnea, pre-syncope, and syncope. The exact incidence is unknown but is estimated that moderate to severe symptoms from pacemaker syndrome occur in approximately 5% to 7% of patients in whom the ventricle is mostly paced, and mild symptoms occur in up to 10% of patients undergoing VVI pacing. In the Mode Selection Trial in Sinus-Node Dysfunction (MOST) trial, 2010 patients with sinus node dysfunction were randomized to DDDR pacing (n = 1014) or VVIR pacing (n = 996). During a median follow-up duration of 33.1 months, 18.3% of patients receiving VVIR pacing crossed over to DDDR pacing because of severe pacemaker syndrome (representing 48.9% of all crossovers in the study), with a median time to crossover of 58 days [3]. Interestingly, the rate of system revision for pacemaker syndrome was only 0.3% at 12 months in the Micra AV post-approval registry [4]. However, based on the leftward shift of this patient's heart rate histograms with heart rates predominantly <80 bpm that would not increase to >80 bpm during activity, he was also diagnosed with symptomatic sinus node dysfunction and chronotropic incompetence. Because his Micra AV LP only provided ventricular pacing, he was offered an upgrade to a dual chamber LP system (Abbott Aveir DR) to provide rate responsive atrial pacing. After having this done successfully, his symptoms significantly improved, and he had enhanced exercise capacity. During his most recent follow-up, 1 year after his dual chamber LP upgrade, he has been 46% atrially paced (0% ventricularly paced). While being programmed to AAIR 60 with VVI backup at 40 (to optimize battery longevity by turning off implant-to-implant communication of the dual chamber leadless system), his estimated atrial LP battery longevity is 13.2 years and ventricular longevity is 15.4 years. Pacemaker syndrome can occur with single chamber ventricular LPs, especially when ventricular LPs do not provide completely reliable AV synchrony nor atrial pacing for sinus node dysfunction. When utilizing ventricular LPs, it is important to periodically assess for signs and symptoms of pacemaker syndrome associated with leadless pacemakers (“leadless pacemaker syndrome”). If this is suspected, further investigation with external ECG monitoring, exercise testing and dynamic pacemaker interrogations can help elucidate the diagnosis. Adjustment or modification of the pacing system can remedy leadless pacemaker syndrome [5], and careful consideration regarding device selection should be made to avoid this problem [6]. The author received no specific funding for this work. J.I.—Abbott: consulting, steering committee, speaking honoraria; Medtronic: consulting; Boston Scientific: data safety monitoring committee, speaking honoraria. The data that support the findings of this study are available from the corresponding author upon reasonable request.