New-Onset Left Bundle Branch Block in Post-Operative Transcatheter Aortic Valve Replacement: To Pace, or Not to Pace?

Conduction disturbances requiring permanent pacemaker implantation (PPI) are known complications of transcatheter aortic valve replacement (TAVR) procedures. Given the location of the aortic valve annulus in the annular fibrocartilage adjacent to the atrioventricular node (AVN) and His-Purkinje system, atrioventricular block (both low and high grade) as well as bundle branch block occurs frequently.^1,2 The majority of new-onset left bundle branch block (N-LBBB) occurs within 24 hours of TAVR (85-94%).³ Tissue inflammation, edema, ischemia, and physical inhibition due to manipulation in the left ventricular outflow tract (LVOT) and aortic valve annulus area during valve implantation have been hypothesized to contribute to N-LBBB.⁴ This does not always persist, with the presence of LBBB decreasing to 44-65% at 30 days.⁵ Although the majority of patients develop N-LBBB in the immediate perioperative state, a small percentage of patients develop sub-acute N-LBBB >24 hours post procedure (6.6-17.8%), with an even smaller percentage presenting as late onset within 1 year after discharge (0-2.9%).³

Earlier valves to market included the Medtronic CoreValve System (MCVS, Medtronic) and the Edwards Sapien Valve (ESV) systems (Edwards Lifesciences). Among the myriad of predictors evaluated across studies, the strongest predictors of N-LBBB include larger valve size (odds ratio [OR]: 4.1 for MCVS 26 mm vs 23 mm;⁶ OR: 3.12 for ESV 29 mm vs 20-23 mm⁷), increased depth of implantation (OR: 1.15-1.4),³ and over-expansion of aortic annulus (OR: 1.8 for 1%; OR: 5.3 if >15%).^8,9 The length of skirt, self-expanding nitinol properties of the MCVS, and the ability to deform into a more traditional LVOT ellipsoid shape has been known to provide asymmetric radial forces, resulting in inflammation and ischemia in the LVOT and septal areas adjacent to the conduction system.^10,11 As such, given the fundamental size and implantation type differences of the self-expanding MCVS vs balloon-expandable ESV systems, MCVS use is an independent predictor of N-LBBB as well (OR: 2.5-8.5).³

Not all conduction abnormalities result in the need for PPI. Strong predictors of PPI include baseline right bundle branch block (risk ratio [RR]: 2.89), intraoperative AV block (RR: 3.49), posterior fascicle hemiblock (RR: 1.14), left anterior fascicle block (RR: 1.62), and first-degree AV block (RR: 1.52).¹² In comparison, baseline LBBB was noted to be equivocal (RR: 1.04). Given the self-expanding nature of the MCVS, the PARTNER trial noted progression of post-TAVR conduction abnormalities to high-degree AV block (HAVB) in 45% of patients with self-expanding valves (MCVS) vs 8% of patients with balloon-expandable valves (SAPIEN and SAPIEN XT, Edwards Lifesciences).³ As such, the MCVS is also noted to be an independent predictor of PPI post-TAVR (RR: 2.54).¹² Other weak predictors include underlying atrial fibrillation (RR: 1.16), male gender (RR: 1.23), and age >80 (RR: 1.17), although deemed not as strong.¹² It has long been known that N-LBBB is associated with increased mortality particularly in the heart failure population, which has resulted in frequent PPIs among patients with N-LBBB post-TAVR. This was initially felt to be needed to mitigate the risk of further progression of conduction block as seen with the MCVS. This bias has persisted despite a newer generation of valves with a lower incidence of progression.

Newer iterations of these valves have been designed to improve success rates and mitigate complications as well. Although a decrease in paravalvular regurgitation was noted, the SAPIEN 3 valve system (Edwards Lifesciences) had no significant
improvement in the rate of new N-LBBB (11% SAPIEN XT vs 13.3% SAPIEN 3), and had a higher PPI rate (12.2% SAPIEN XT vs 19.1% SAPIEN 3).¹³ Patients with PPI were noted to have a lower valve implantation height (66.5% vs no PPI 72.3%) and greater degree of valve oversizing (mean=10.9%), with 40% of patients requiring PPI having a 10-20% valve oversizing percentage.¹³ The pivotal and post-market approval studies for the original MCVS noted high PPI rates of 44.9%. In comparison to the prior MCVS, the newer Evolut valve (Medtronic) has substantially decreased the high PPI risk, with a PPI rate of 22.9%.¹⁴ Preliminary results from a single-center retrospective study of the new LOTUS valve (Boston Scientific) at our institution demonstrate N-LBBB rates of 69.4%, with a low PPI rate at 18.6%.¹⁵ Small studies of other newer valves also note lower PPI rates, including rates as low as 9.1% for the JenaValve system (JenaValve) and 10.0% for the ACURATE neo valve (Boston Scientific).^16,17 Comparison of N-LBBB and PPI rates among different valve types are shown in Tables 1 and 2.

As indications for TAVR expand, there are increasing numbers of TAVR, and thus, subsequent N-LBBB and PPI after TAVR. Regardless, there remains a positive correlation between TAVR-induced N-LBBB and mortality, which is not eliminated by PPI. A meta-analysis by Xi et al showed that PPI had no significant effect on cardiovascular mortality (heart failure and stroke or myocardial infarction) after TAVR.¹⁸ In comparison, Regueiro et al noted an increased risk of cardiac death with TAVR-induced N-LBBB, yet no difference in all-cause mortality at 1 year.¹⁹ The PARTNER II trial and S3 registry demonstrated that N-LBBB at discharge was associated with greater all-cause mortality, rehospitalization rate, cardiovascular death, and higher PPI rates.²⁰ N-LBBB was noted to be higher in MCVS vs SAPIEN XT and SAPIEN 3 valve systems. Other predictors of mortality post-TAVR included older age, male gender, COPD/asthma, and history of cancer, and were all associated with higher hazard ratios (HR). In addition, prior cerebrovascular accident (HR: 1.67), prior atrial fibrillation or flutter (HR: 1.65), and anemia (HR: 1.61) also demonstrated a significantly increased risk. However, N-LBBB at discharge (HR: 2.09) remained the strongest independent predictor of mortality.²⁰ 

Despite the mortality risk of N-LBBB as noted by the PARTNER II trial and S3 registry, PPI has shown limited to no clinical benefit in this particular population. Chamandi et al noted that PPI in patients with N-LBBB resulted in no change in sudden cardiac death (SCD) (P=0.798), all-cause mortality (P=0.804), cardiovascular death (P=0.919), heart failure admission (P=0.437), composite mortality and heart failure (P=0.594), and composite cardiovascular mortality and heart failure (P=0.738) at 3-year follow-up post-TAVR.²¹ Importantly, this study highlights that pacing for N-LBBB does not alter outcomes post-TAVR, especially the risk of sudden cardiac death. Interestingly, Urena et al noted a 5-fold increased risk of SCD in patients with N-LBBB with QRS >160 ms at 1-year post-TAVR.^21,22 The size and extent of the patient population affected and the potential mortality impact of N-LBBB presented by the PARTNER II trial and S3 registry are difficult to refute. 

A potential reason why N-LBBB post-TAVR increases mortality is the result of newly induced ventricular dyssynchrony with a resultant increased risk of heart failure and SCD. Traditional right ventricular based pacing does not correct N-LBBB dysynchrony, and may in fact be worse than native LBBB.²³ This would explain why PPI for N-LBBB does not mitigate the increase in mortality. Thus, it would be important to consider more physiologic forms of pacing for patients with N-LBBB post-TAVR. Patients with LBBB from true conduction abnormalities are known to have a greater degree of left ventricular dyssynchrony even when compared to patients with interventricular conduction delay due to ischemic myocardial dysfunction.²⁴ Such patients are known to respond better to cardiac resynchronization therapy (CRT) compared to ischemic patients. Furthermore, according to the PARTNER trial, among post-TAVR patients with baseline reduced LVEF of <35%, those with N-LBBB were noted to have less improvement in LVEF than those without N-LBBB.²⁵ Over time, true N-LBBB is noted to eventually induce heart failure. As such, the observation by Nazif et al, similar to the known reduction in LVEF among pacemaker patients with traditional RV pacing, further begs the question of whether N-LBBB post-TAVR may benefit from CRT.²⁶

His bundle or selective left bundle branch pacing may provide an alternative approach in this population. In a small study of 16 patients post-TAVR with MCVS, De Pooter et al demonstrated successful His bundle capture in 69% (11 of 16) of patients with failure noted due to inability to recruit the His bundle (2 patients), no LBBB capture despite His bundle capture (1 patient), or unacceptably high output (1 patient).²⁷ When successful, physiologic pacing was achieved with significant QRS narrowing (from 162 ms to 99 ms) and was stable at an average follow-up of 11.4-months.²⁷ As such, it seems reasonable that physiologic pacing with CRT, His bundle, or selective left bundle branch pacing²⁸ post-TAVR could mitigate the increased mortality risk associated with N-LBBB. An example of selective His bundle pacing and selective left bundle branch pacing is shown in Figure 1.

A recent consensus paper by Rodes-Cabau et al on post-TAVR management of conduction disturbances recommends a mix of cautious observation in the acute post-procedural time frame and vigilant early intervention.²⁹ Currently, temporary post-TAVR pacing for 24 hours is recommended for any new conduction abnormalities, including progression of underlying conduction abnormalities, N-LBBB, or HAVB. Patients with no EKG changes without pre-existing RBBB, or progression of PR or QRS duration <20 ms with pre-existing RBBB, are deemed low risk for progression to HAVB and considered stable for discharge. In patients with N-LBBB, early resolution or improvement with QRS <150 ms and PR <240 ms noted within 24 hours post procedure, temporary pacemaker removal and early discharge on day 2 post-TAVR is recommended. PPI is recommended if persistent HAVB post procedure or recurrence is noted, even after temporary pacemaker removal. However, studies have shown that several high-risk groups noted signs of delayed progression of conduction disease to HAVB even if not fulminantly present prior to discharge. N-LBBB with persistence of QRS >150 ms or PR >240 ms, as well as prolongation of PR or QRS >20 ms in patients with pre-existing conduction abnormalities including RBBB, LBBB, IVCD with QRS ≥120 ms, or first-degree AV block, have been associated with a high risk of delayed progression to HAVB and sudden cardiac death. Unfortunately, no consensus therapeutic steps have been shown to be effective yet in mitigating this risk in these groups. As such, in these patients, invasive electrophysiologic study, continuous ambulatory ECG monitoring at hospital discharge, or PPI (particularly in patients with QRS >150 ms) have been proposed as options to mitigate life-threatening arrhythmia and sudden cardiac death.²⁹ We would propose that if the decision is made to perform PPI, one should consider physiologic pacing such as CRT or His bundle pacing to mitigate the effects of induced ventricular dysynchrony. However, the potential benefit of more physiologic forms of pacing in this population of N-LBBB post-TAVR have yet to be demonstrated in a randomized, prospective clinical trial, and thus, warrants further clinical investigation.

Disclosures: The authors have no conflicts of interest to report regarding the content herein.

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