By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SYNOPSIS: A study of the latest-generation balloon-expandable valves demonstrates a higher rate of new conduction abnormalities and pacemaker implants than previous models, and identifies patient- and procedure-related variables that affect these outcomes.
SOURCE: Husser O, et al. Predictors of permanent pacemaker implantations and new-onset conduction abnormalities with the SAPIEN 3 balloon-expandable transcatheter heart valve. JACC Cardiovasc Interv 2016;9:244-254.
New conduction abnormalities requiring permanent pacemaker implantation are generally considered to be more common following transcatheter aortic valve replacement (TAVR) than after surgical aortic valve replacement, and are an important limitation of this mode of therapy. Historical numbers suggest a wide range of pacemaker rates across studies, with clear differences among valve platforms. A recent meta-analysis of 41 studies involving 11,210 TAVR patients reported median pacemaker rates of 28% for the self-expanding Medtronic Corevalve system, and 6% for the balloon-expandable Edwards Sapien valve.
The recently approved Edwards Sapien 3 valve includes several major improvements over previous generations, including smaller introducer size, greater control of deployment, and an outer sealing skirt to reduce paravalvular leak. Along with these enhancements, however, come reports of significantly higher pacemaker rates for this device.
Husser et al examined the determinants of new conduction system abnormalities and pacemaker implantation in a series of 244 consecutive patients receiving the Sapien 3 valve at their institution in Munich. Patients with existing pacemakers, bicuspid valves, or valve-in-valve procedures were excluded, leaving a study group of 208 patients. The resulting group was a relatively typical TAVR population, with a mean age of 81 years and a logistic EuroSCORE of 16%. The 23-, 26-, and 29-mm valve sizes were used in 44%, 38%, and 18% of cases, respectively. Thirty-nine percent of cases were performed with conscious sedation, and 98% of cases achieved device success.
Sixteen percent of patients required pacemaker implantation prior to hospital discharge. New-onset or worsened conduction abnormalities occurred in 17% of patients — left bundle branch block in 16% (25 of 184 without pre-existing conduction disease) and right bundle branch block (RBBB) in 1% (2 of 184). As in prior publications, multivariate analysis showed that baseline electrocardiographic abnormalities were predictive of new pacemaker requirement, including RBBB, atrial fibrillation, and bradycardia.
Implantation depth, measured at the nonseptal side and expressed as percent of the frame height below the aortic annulus, was found to be an independent predictor of new or worsened conduction abnormalities or pacemaker. The degree of oversizing was calculated in standard fashion using data from multislice CT scans and the nominal expanded size of each bioprosthetic valve. The median percentage oversizing was 7% by area and 2% by perimeter measurements. No significant association was found between the overall degree of oversizing and need for permanent pacemaker. However, among the 19 cases that were oversized beyond the manufacturer’s recommendations, so-called out-of-range oversizing, the rate of new or worsened conduction abnormality or pacemaker was a very high 58% vs 28% for the remainder of the population (P = 0.007).
The authors concluded that in this large single-center TAVR study, the need for permanent pacemaker or the occurrence of new or worsened conduction system disease occurred in one-third of patients receiving the Sapien 3 valve. Additionally, the authors noted a clear relationship between implantation depth and extreme valve oversizing. They suggested that careful attention to implantation depth and valve sizing may have the potential to reduce pacemaker rates and should be the subject of future study.
COMMENTARY
It is noteworthy that advances in TAVR technology that afford benefits in one area (sealing of paravalvular leak, in this case) may be associated with greater risks in another. The one in three risk of conduction abnormalities observed in this study is higher than what has been reported with prior iterations of the Edwards balloon-expandable TAVR valve.
The patient-level variables associated with new pacemaker requirement in this study, most notably RBBB, atrial fibrillation, and baseline bradycardia, are obviously not modifiable for particular patients, but may affect patient selection and counseling. Both TAVR centers and referring providers should be aware of these variables. The suggestion that implanters may affect pacemaker rates through attention to implant depth is intriguing. It is notable that this study’s expression of implant depth as a percentage of frame height below the annular frame is a non-standard measure that will be unfamiliar to most. Communicating depth in terms of millimeters below the annular plane would be both more intuitive and more directly useful to practitioners.
New conduction system disease, most prominently that requiring permanent pacemaker implantation, is a major limitation of the TAVR procedure. Nearly every study to date has demonstrated pacemaker rates following TAVR that are significantly (and sometimes strikingly) higher than those expected after surgical AVR. This issue has had an effect on the care of TAVR patients since the inception of this procedure, but has scarcely affected choice of therapy for those patients at prohibitive surgical risk. Recently, the FDA granted approval for the PARTNER III trial, which will study the Sapien 3 valve in patients with low predicted risk of mortality from surgery (STS score < 4). As TAVR is applied to intermediate and even low-risk patients, and in particular to younger patients, the pacemaker issue will loom larger in the risk/benefit calculation surrounding this procedure.
