Aortic stenosis (AoS) is the most common valve disease in developed countries, affecting approximately 3% of the population older than 75.1 In Brazil, with an increase in life expectancy, a significant increase in cases of degenerative AoS is expected for the coming years.2

The mortality rate of patients with symptomatic AoS is approximately 50% in the first 2 years with no surgical treatment.3^,4 Aortic valve replacement is associated with low mortality when performed in patients without severe comorbidities.5 However, at least 30% of symptomatic patients with severe AoS are not operated because of the presence of comorbidities, ventricular dysfunction or old age.6^,7 A less invasive form of treatment would be an attractive alternative for patients with high surgical risk.

Transcatheter aortic valve implantation (TAVI) is a recently developed technique for the treatment of symptomatic patients with severe AoS considered to be inoperable or at high surgical risk.8^-13 The 2 types of aortic valve prosthesis most used for percutaneous implantation are: A CoreValve^® (self-expanding) and Sapien^® (balloon-expandable).11^,12^-16

Percutaneous implantation has evolved a lot over the past years, but it presents some challenges. Conduction disorders requiring permanent pacemaker implantation are among the main complications of the procedure. TAVI is associated with a greater need for pacemakers compared to surgery, particularly when the CoreValve^® prosthesis is used.17^-24

In addition to the greater need for permanent pacemaker implantation, a higher incidence of intraventricular conduction disorders has been demonstrated, notably left bundle branch block (LBBB) after TAVI. Several authors have shown that the development of LBBB after TAVI is associated with a greater need for pacemaker, ventricular dysfunction and increased long-term mortality.25^-27

The objectives of this study are to determine the incidence of new conduction disorders and the need for a permanent pacemaker after TAVI, to identify predictors of the need for a permanent pacemaker, and to conduct an exploratory analysis to describe the long-term mortality of patients who developed conduction disorders.

Retrospective study. The study included all patients undergoing TAVI in a major public cardiology hospital from December 2011 to June 2016. TAVI was recommended for patients with severe AoS considered to be inoperable or at high surgical risk by a Heart Team of clinical cardiologists, interventional surgeons and cardiac surgeons. The decision of surgical risk was obtained by calculating the EuroSCORE I.28 The decision on the best form of treatment - clinical, surgical or TAVI - was taken by the Heart Team, considering the risk assessed by Euroscore and other variables not considered in the score but increased the surgical risk, such as the presence of porcelain aorta, fragility level, hostile chest and cirrhosis of the liver.

The feasibility of TAVI was determined after analysis of tomographic images from aortic measurements, aortic ring diameter, coronary artery height and femoral artery caliber. Some factors involved in planning the procedure, such as the best access route and the type and size of the prosthesis to be implanted, were defined by the surgical and interventional team after analysis of tomographic images. The prostheses used were CoreValve^® from Medtronic, Sapien^® from Edwards and Inovare^® from Braile. The access routes were transfemoral, transapical, transaortic and the subclavian artery. Transfemoral access was the preferred route in the absence of severe iliac or femoral artery disease. The transapical access route was recommended for patients with inadequate vascular access. The prostheses used for transapical access were Sapien^® and Inovare^®. All implants were performed under general anesthesia. Temporary transvenous pacemaker was implanted in all patients before the procedure and maintained for at least 48 hours.

The study was approved by the local research ethics committee and all patients undergoing TAVI signed an informed consent.

All data were collected by the first author of this manuscript by reviewing medical records. The electrocardiograms available in the medical records were ordered according to the dates they were taken. These electrocardiograms were divided into 4 groups: Pre-TAVI ECGs, ECGs taken after TAVI but still in the intensive care unit, ECGs after TAVI taken at the ward and ECGs taken at outpatient follow-up. The ECGs were analyzed independently by the author and a second cardiologist. The electrocardiographic reports followed the criteria defined by the Brazilian Guidelines on Electrocardiography.29

The criterion used to recommend a permanent pacemaker still in the operating room after the TAVI was implanted was the presence of high-grade AVB or intrinsic rhythm of less than 40 beats per minute during inhibition of the temporary pacemaker. Recommendations of a permanent pacemaker while in hospital were determined by a team of clinical cardiologists, electrophysiologists and intensivists, considering the Brazilian and European guidelines for the implantation of artificial cardiac pacing devices.30^,31

The benefits of TAVI include: improved functional class and quality of life, increased ejection fraction and increased short- and long-term survival.9^-12 Despite some favorable clinical outcomes, complications such as the development of LBBB and AVB requiring pacemakers are a source of concern.

The high incidence of conduction disorders after TAVI can be explained by the anatomical proximity of the conduction system to the aortic valve.32 TAVI involves the exclusion of valve tissue by the prosthesis and compression of the annulus and adjacent structures, including the fibrous skeleton of the heart and the conduction system. A necropsy study of a patient who had CAVB after TAVI demonstrated the presence of a hematoma in the interventricular septum that compressed the bundle of His.33

In this study, 77% of the patients developed new conduction disorders during index admission. These findings are identical to those described by Fraccaro et al. in 64 patients undergoing TAVI,24 and very similar to those described in the studies by Calvi et al., who found new conduction disorders in 68% of the 30 patients who underwent the procedure.23

In this study, it was found that 30.7% of the patients developed LBBB. This finding is similar to that described by Houthuizen et al., who found a new LBBB in 34% of the 679 patients who underwent TAVI.25 The incidence of LBBB after TAVI can range from 4 to 65% depending on the prosthesis used. According to Martinez et al., the frequency of a new LBBB after the implantation of a self-expanding prosthesis ranges from 22 to 65%, while with the use of a balloon-expandable prosthesis, it ranges from 4 to 30.2%.34 In the study by Testa et al., the onset of LBBB after TAVI was observed in 43% of the 1,060 patients treated with the CoreValve® prosthesis. According to this author, the presence of LBBB is associated with a higher rate of pacemaker implantation up to 30 days after TAVI.26

Sixteen of the 53 patients (30.2%) included in this study had a permanent pacemaker implanted during index admission. In a review of 42 studies, the recommendation for pacemaker implantation after TAVI ranged from 4 to 51%.19 The highest incidence was described by Akin et al.17 and the lowest one was found in the study by Eltchaninoff et al.16

The risk factors for the need for a permanent pacemaker after TAVI found in this study in the univariate analysis were: use of CoreValve^® prosthesis, implantation of larger prostheses, QRS complex ≥ 120 ms and first-degree AVB. In this study, all of the 16 patients who needed a pacemaker had the CoreValve^® prosthesis implanted. Other authors also demonstrated that the need for a permanent pacemaker with the CoreValve^® prosthesis is significantly higher compared to the Sapien^® prosthesis.16^-19^,21^-24 In the study by Piazza et al., who used the CoreValve^® prosthesis, the pacemaker implant rate was 19% in 91 patients evaluated.22 In the PARTNER study, which used Sapien^® prostheses, this rate was 3.8% in 699 patients evaluated up to 30 days after the procedure.10 In the study by Aktug et al., 20 of the 72 patients (28%) who had the CoreValve^® prosthesis implanted required a permanent pacemaker, whereas only 4 of the 82 patients (5%) who had Sapien^® implanted required the device.35

Due to its longer length (53 to 55 mm), the CoreValve^® prosthesis extends from the ascending aorta to the LV outflow tract. During implantation, the lower third of the prosthesis may compress the interventricular septum and the conduction system.19^,22^,24^,36 The Sapien^® prosthesis extends a few millimeters below the annular plane. The lower incidence of conduction disorders with the Sapien^® prosthesis is due to a higher implant and less extension of the prosthesis in the LV outflow tract.19^,22^,24

The implantation of larger prostheses was associated with a greater need for pacemakers in this study. The mean prosthesis size of patients who had pacemaker implanted was significantly higher than that of those who did not have any pacemaker implanted. The implantation of larger prostheses was also a predictor of the need for pacemakers after TAVI in a multicenter study that evaluated 243 patients in the UK.36

The presence of previous conduction disorders is a risk factor for the development of AVB in both conventional surgery and TAVI.19^,20 In this study, patients with history of first-degree AVB had a 13-fold higher risk of pacemaker implantation compared to those without first-degree AVB. The presence of first-degree AVB before TAVI was also a predictor of the need for pacemakers in the FRANCE-TAVI Registry16 and in the studies by De Carlo et al. and Bleiziffer et al.37^,38

In this study, patients with QRS complex duration ≥120 ms had a 5-fold increased risk of pacemaker implantation compared to those who did not have the same ECG finding before TAVI. The presence of previous conduction disorders was an independent predictor of the need for pacemakers in a meta-analysis published by Siontis et al.19

In the multivariate analysis, the only variable considered to be an independent predictor of the need for pacemaker implantation after TAVI was the presence of first-degree AVB before implantation of the prosthesis. It should be noted that this is a retrospective design study that reports the initial experience of a single center with a small sample size. Thus, the multivariate analysis presented has low statistical power, which means that there is a considerable chance of type II error. Despite these limitations, the results found were similar to those described in the literature.

Other factors associated with the development of conduction disorders after TAVI, such as depth of self-expanding prostheses and calcification in the outflow tract were not evaluated in this study. The excessively low valve implantation was associated with the development of conduction disorders after TAVI in some series published in the literature.19^,22^,24 Piazza described a significant correlation between the depth of the implant in the LVOT and the onset of LBBB after implantation of self-expanding prosthesis.22

History of conduction disorders after TAVI is not well understood yet, because it is a relatively new technology and further studies are required to say the best course of action to be taken in the development of conduction disorders. Implantation of permanent pacemaker after TAVI is justified among seniors with cardiac structural disease. Potential problems related to the use of provisional transvenous pacemaker, such as ventricular perforation, infection, prolonged immobilization and longer hospital stay, contribute to reduced threshold of indication of permanent artificial cardiac pacing. It is known that displacement of the electrode of the provisional pacemaker can cause catastrophic failures with potentially serious consequences, exposing the patient to the risk of asystole and death. These facts justify the decision of implanting permanent pacemaker earlier, a conduct supported by experts, but not based on the results of randomized studies, as these are not available in this particular situation.39

On the other hand, implantation of permanent pacemaker is also not risk-free. Elderly patients with multiple comorbidities have an increased risk of hematoma, pocket infection and endocarditis. Besides, cardiac pacing may lead to interventricular dyssynchrony and worsening of long-term ventricular function.40 In a sub-analysis of the PARTNER study, the presence of pacemaker was an independent predictor of mortality in one year.21

In this study, 8 of the 9 patients who died during follow-up had either LBBB or permanent pacemaker. Houthuizen et al. demonstrated an association between new LBBB after TAVI and increased mortality.25 The 60% increase in 1-year mortality in patients who developed new LBBB after TAVI in the study by Houthuizen et al. suggests that the onset of LBBB after TAVI is a serious complication, which attenuates the benefit achieved by the procedure.

It should be noted that in this study the prostheses used were first-generation prostheses. Despite the technological development of the new prostheses and the experience gained with the procedure, the incidence of conduction disorders after TAVI is still a source of concern and has inconsistent results depending on the prosthesis used. The need for a permanent pacemaker is at least 2-fold higher after Sapien3^® implantation compared to the first generation Sapien^® prosthesis.39 The need for a permanent pacemaker using the Medtronic Evolut^® prosthesis is lower (11.7 - 25%) compared to the CoreValve^® prosthesis (9 - 38%), although with a relatively high incidence.39

Conduction disorders requiring permanent pacemaker implantation remain a common complication after TAVI and may have a negative impact on the patients’ prognosis.21^,25^,26^,27^,39 Strategies to reduce these complications are of great importance before extending TAVI to low-risk patients in whom these complications may have an even greater impact on prognosis.

TAVI caused the development of conduction disorders in the vast majority of patients. Seventy-seven percent of the patients developed new conduction disorders, the most frequent of which is complete AV block (32%) and left bundle branch block (30%).

Approximately 30% of the patients required a permanent pacemaker implanted during hospitalization.

A QRS complex with duration ≥ 120 ms, the presence of first-degree AVB, implantation of larger prostheses and the use of CoreValve were associated with the need for a permanent pacemaker in the univariate analysis.

In the multivariate analysis, the only variable considered to be an independent predictor of the need for pacemaker implantation after TAVI was the presence of first-degree AVB.

The survival of patients who developed new conduction disorders after TAVI was numerically worse than the survival of the rest of the population. This result was not statistically significant. The lack of statistical significance can be attributed to the relatively short analysis time and small sample size.