Intermittent Loss of Capture: A Forgotten Phenomenon at Play

A 55-year-old lady with a history of ischemic cardiomyopathy/congestive heart failure (NYHA class II) presented with syncope. She was receiving guideline-directed medical therapy including beta-blockers (carvedilol 3.125 mg twice daily) but no other antiarrhythmic medications. The presenting 12-lead electrocardiogram (ECG) revealed ventricular escape rhythm (rate of 35 bpm) followed by hemodynamically stable fascicular rhythm (50 bpm). A few hours later she reverted to sinus rhythm (60 bpm) with aberrantly conducted QRS complexes notable for left axis deviation and poor precordial R wave progression. Telemetry also revealed episodes of nonsustained monomorphic ventricular tachycardia. She then underwent a successful permanent transvenous dual-chamber cardiac defibrillator (EVERA DR MRI, Medtronic, Illinois, US) implant. The atrial lead was placed in the right atrial appendage and the defibrillator coil lead in the right ventricular apical septum. Sensing and pacing parameters during the implant were satisfactory for both leads. On postprocedure Day 1, a routine 12-lead ECG (Figure 1A) showed intermittent atrial capture. The programmed parameters for bradycardia therapy are showcased in Figure 1A. A concurrent chest x-ray (Figure 1B) confirmed both leads in their respective intended locations. Figures 2A and B showcase atrial capture threshold testing at faster and slower rates. What are the possible mechanisms at play? Atrial pacing spikes are denoted by solid one-sided arrows in Figure 1A. Captured P-waves are followed by nonpaced wide QRS complexes (A) at a constant PR interval (200 ms) suggestive of intrinsic atrio-ventricular (AV) conduction with aberrancy. Atrial loss of capture as expected initiates a paced AV delay, which is terminated by a ventricular paced complex (inverted solid triangle). In addition, nonpaced QRS complexes (A' and B) occurring at shorter R-R cycle lengths warrant additional scrutiny. The similarity between QRS morphology of A and A' plausibly favors the latter as a conducted rather than a fascicular/ventricular premature complex. Its preceding intrinsic P-wave is expected to fall within the postventricular atrial refractory period (PVARP) and be annotated as a “sensed-refractory” atrial event (AR). Therefore, the ensuing conducted QRS is likely denoted as a ventricular premature beat (due to lack of prior atrial-sensed or AS event) triggering a modified atrial-based timing that starts a ventriculo-atrial escape interval (VAEI) terminated by an atrial-paced (AP) event [1]. This hypothesis is readily adjudicated by back-tracking from the APto A' to yield the correct VAEI of ∼ 560 ms (onset of ventricular sensing is expected to be slightly delayed from the onset of QRS, allowing for some discrepancy). The other nonpaced QRS complex B is indeed different from the previously established conducted QRS morphology. This also happens at a slightly longer R-R cycle length (460–480 ms) compared to that associated with A' (420–440 ms). One possible explanation is a fascicular/ventricular premature beat with or without a preceding P-wave. The other possibility is a conducted QRS with a variation in degree of aberrancy. Any presumed P-waves (conducted or not) in the above two scenarios are also likely to be AR events. The variability in R-R intervals is due to a combination of paced ventricular events (inverted solid triangles) and appropriately sensed intrinsic QRS complexes (A, A', and B) occurring at different coupling intervals. The apparent violation of the LRL (>860 ms) in the ventricle, whenever noted, is readily explained on the basis of the default atrial-based timing of the Medtronic pacemaker [1]. Herein, longer R-R intervals (920–980 ms) mechanistically linked to AP are between intrinsically conducted (shorter PR intervals seen with A) and paced (long paced AV delay) QRS complexes. There is a definite notable pattern to the intermittent loss of atrial capture. AP spikes associated with loss of capture occur at longer cycle lengths (lower rate limit or LRL ∼ 860 ms) following the captured atrial beats. The latter themselves paradoxically occur at shorter cycle lengths (730–800 ms) following the presumed intrinsic P-waves (likely in the case of A' and plausible in the case of B). The origin of intrinsic P-waves is as speculated. First, loss of atrial capture followed by ventricular pacing is a known setup for retrograde atrial conduction. “Echo” beats (dual AV nodal physiology) may then be postulated to explain any subsequent conducted QRS complexes. Alternatively, an atrial focus (sinus/ectopy/parasystole) itself may be invoked. To surmise, the phenomenon showcased here is best interpreted as paradoxical loss of capture at longer atrial cycle lengths (AP Capture-AP Loss of Capture) but not at shorter cycle lengths (Intrinsic P-waves-AP Capture). We validated this hypothesis by demonstrating a commensurate lower atrial capture threshold at faster atrial pacing rates (0.75 V/0.4 ms at 120 bpm vs. 2.5 V/0.4 ms at 60 bpm; Figure 2). The most apt explanation here is that atrial depolarization engenders a time-interval-sensitive electrotonic facilitation (window of favorable threshold) for subsequent atrial capture [2, 3]. In Figure 1A, it is therefore presumable that atrial noncapture results when the atrial pacing spike falls after this facilitation window period is expired. The threshold for these noncaptured beats is therefore expected to be higher than the programmed output of 3.5 V/0.4 ms. It is to be noted that atrial threshold testing at a constant pacing rate of 60 bpm yielded values that were lower than the resting state ECG (Figure 1A). Once again, Wedensky electrotonic facilitation is posited as an explanation based on the constancy of atrial pacing and gradual amplitude decrements from higher values. An alternative/related mechanism of capture at shorter but loss of capture at longer cycle lengths may be related to phase 4 depolarization. Herein, gradual outward diastolic decay currents render the membrane pathologically partially depolarized without a regenerative action potential. The ensuing prolonged postpartial depolarization-induced refractoriness (pathologically extended refractory periods) is grouped under the umbrella term of post repolarization refractoriness. A diastolic impulse timed before the onset of such a state succeeds in invoking a regenerative action potential (capture in our case), while later ones fail (loss of capture). In this regard, subsequent spontaneous atrial depolarization from a disparate site is expected to alleviate this altered state of refractoriness at the lead-tissue interface (Figure 1). This is akin to the phenomenon where premature ventricular beats originating distal to the site of phase 4 block in a diseased conduction system can retrogradely hyperpolarize the partially depolarized membrane, allowing for resumption of conduction. In our case, increased capture threshold at a slower atrial paced rate (Figure 2B) is not eloquently explained by isolated phase 4 depolarization. This is because of initial capture followed by loss of capture at the same slower rate. The authors wish to highlight that a partially depolarized refractory membrane can result from other mechanisms as well, including tissue injury (mechanical trauma from leads, ablation), hyperkalemia, ischemia (local hyperkalemia), and so forth. In some instances, intravenous adenosine/adenosine triphosphate can restore excitability by hyperpolarizing the partially depolarized membranes (by opening specific potassium channels) [4-6]. The patient was managed by increasing the LRL to 80 bpm, which achieved consistent atrial capture at outputs of 3.5 V/0.4 ms with an underlying threshold of 1.75 V/0.4 ms. At a 1-month follow-up device check, the same phenomenon continued to exist, indicating that it was not a periprocedural acute entity. Consistent atrial capture was noted in the ongoing ECG, and hence, no further troubleshooting was performed. The authors at present report a 1-month follow-up with replication of the same phenomenon and pacing thresholds. In summary, lead-tissue interface related trauma/injury (with or without coexisting local pathology) is speculated to instigate a coexistent state of altered membrane excitability/refractoriness through various mechanisms. The interesting capture responses noted under different pacing/rate-related conditions can be posited to some overlooked phenomenon such as electrotonic facilitation and/or partially depolarized membranes (bradycardia dependent/independent). The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.