Uni vs. Bi: What to Do When They Don’t See Eye to Eye?

A high burden of premature ventricular contractions (PVCs) may result in cardiomyopathy and has been associated with increased mortality risk.^{1, 2} In patients with symptomatic, monomorphic PVCs without underlying structural heart disease, catheter ablation is recommended for symptom relief and management of left ventricular (LV) dysfunction.³ Radiofrequency ablation of PVCs is typically guided by activation mapping to determine the earliest local activation time (LAT), and thus, the site of origin of the PVC. Present electroanatomic mapping systems typically annotate LAT based on the maximum downslope (-dV/dt max) of the unipolar electrogram recordings. This is based on the principal that the maximum intracellular voltage gradient at the leading edge of a wavefront is represented and matched by an equally inverse change in extra-cellular potential.⁴ However, the presence of far-field signals in unipolar electrograms can make accurate determination of LAT difficult in clinical practice. Additionally, these measurements were originally validated in two-dimensional preparations and may not be consistent in localizing earliest LAT of PVCs arising from deep, three-dimensional, intramyocardial sources.⁴ This raises an important clinical question: is the -dV/dt max of the unipolar electrogram reliable in identifying accurate ablation sites for intramural sources of PVCs?

In this issue of Heart Rhythm, Higuchi et al⁵ address this specific question by evaluating the relationship between unipolar and bipolar electrograms for selection of successful PVC ablation sites originating from endocardial and intramural sources. Endocardial sites were defined as those in which ablation at the earliest site (as marked by high-density mapping) resulted in PVC suppression within ≤10 sec without recurrence, whereas intramural PVCs were defined as those that resulted in delayed PVC suppression (defined as >10 seconds), required more than one ablation application (at the same or adjacent sites), or did not result in complete suppression. They included 66 patients with right and left ventricular outflow tract, LV summit, and papillary muscle PVCs. The first rapid onset of unipolar and bipolar electrograms and -dV/dt max of the unipolar electrogram to QRS onset were analyzed. The authors report that while there is concordance between the first rapid onset of the bipolar deflection and the -dV/dt max of the unipolar electrogram for endocardial PVCs, with both preceding QRS onset by an average of 20.5 and 16.0 msec, respectively, there was discordance between these two measures for intramural PVCs as well as PVCs ablated from the aortic cusps. For successfully ablated intramural PVCs, the first rapid bipolar deflection coincided with the earliest rapid unipolar deflection, which most frequently showed a rS/RS pattern, while the -dV/dt max of the unipolar electrogram occurred after QRS onset, representing the endocardial breakthrough site. In unsuccessfully ablated intramural PVCs, not surprisingly, both the unipolar -dV/dt max and the “earliest” time from the first rapid bipolar deflection to QRS onset were late with respect to QRS onset, with the bipolar deflection occurring on average 3.5 sec after onset of the QRS. For PVCs ablated from the aortic cusps, mismatch between -dV/dt max and early onset of the bipolar and unipolar electrograms were noted, with the onset of bipolar electrogram being early (approximately 21.2 seconds pre-QRS onset), while the -dV/dt max of the unipolar electrogram was 19 msec after QRS onset, potentially indicative of the presence of the adventitia/tissue between the cusps and the surrounding myocardium. Hence, the authors conclude that mapping of intramural PVCs should be guided by the onset of rapid bipolar deflection that corresponds with a similarly early unipolar deflection, noting that this may not correlate with the most -dV/dt of the unipolar electrogram for non-endocardial PVCs.

This study beautifully demonstrates both the value and weaknesses of the unipolar -dV/dt max in mapping of PVCs and the discrepancies that may be observed in bipolar and unipolar recordings when targeting what may be deeper myocardial sources. In addition, the concept of using the most rapid unipolar deflection, rather than focusing on its pattern, bears novelty and is certainly interesting. However, the study also has several limitations. In addition to its retrospective nature, the authors used response to ablation to define “intramural” PVCs. The criteria of using 10 sec to define endocardial versus intramural origin of PVCs is somewhat arbitrary and the lack of immediate suppression may be due to poor selection of ablation targets, and/or suboptimal catheter contact, navigation, and/or stability. Not surprisingly, the majority of failed ablations were in patients who had presumed intraseptal, LV summit, or papillary muscle PVCs. Ablating intraseptal and summit PVCs often requires mapping and/or ablation within the coronary venous system,⁶ which was not consistently performed in this study. Challenges in ablating papillary muscle PVCs include anatomic variability of the papillary muscles and catheter maneuverability and stability.⁷ Without knowing the exact source of the PVC, conclusions regarding electrogram characteristics at the presumed earliest endocardial site may be limited. Successful ablation of truly intramural PVCs is known to require longer lesion delivery, bipolar ablation, use of half-normal saline irrigation, wire mapping, and/or alcohol ablation or coil embolization, and/or open surgical approach.⁸ While this limitation is somewhat mitigated by the use of contact-force catheters for the majority of patients and inclusion of only cases with high density mapping with <5 mm interpolation to define the earliest endocardial sites, it is not entirely overcome by the present design. Finally, it’s also important to note that bipolar electrogram recordings are not perfect and can be affected by the direction of wavefront of propagation and electrode and interelectrode size, which can in turn, affect electrogram morphology and measurements.⁴

Inclusion of patients with high burden of PVCs at baseline (in a bigeminal, trigeminal and quadrigeminal pattern) is a clear strength of the study, as the presence of frequent PVCs at the time of ablation is an important predictor of success and allows for detailed mapping. The level of sedation and use of any catecholaminergic agents presumably remained stable during the procedures, as changes in anesthetic and adrenergic agents may confound PVC burden and ablation outcomes. In addition, this study included patients without presence of ventricular scars, which will impact the relationship of unipolar and bipolar electrograms.

The authors are to be commended for pursuing an important and relevant question in understanding the relationship of observed electrograms to the likelihood of successful ablation sites. The findings of the current study confirm the use of unipolar -dV/dt max in identifying earliest LAT for endocardial PVCs and highlight discrepancies in unipolar and bipolar recordings that may be observed at aortic cusp and “intramyocardial” sites. It’s clear that in cases where the mapped bipolar electrograms are not early with respect to QRS onset, ablation at “earliest” of these endocardial sites is futile. The concept of using the onset of rapid unipolar deflection, though useful, requires further validation. Ultimately, the results of the current study strengthen our understanding of the relationship of unipolar and bipolar electrograms at successful PVC ablation sites. They suggest that bipolar onset and unipolar -dV/dt max may not see “eye to eye” for non-endocardial PVCs, and in these cases, the earliest rapid bipolar deflection onset should guide ablation, perhaps annotated at the first rapid unipolar deflection.