CONDUCTION DISORDERS AND PERMANENT CARDIAC PACEMAKER AFTER TRANSCATHETER AORTIC IMPLANTATION-AN UPDATE OVERVIEW

How to cite this article (APA): Junior A.D.S.M, Ribeiro M.D.F., Laranjeira T.D.A., Barbosa V.A., Fernandes J.F. (2021). Conduction Disorders and Permanent Cardiac Pacemaker After Transcatheter Aortic Implantation An Update Overview. International Journal of Research GRANTHAALAYAH, 9(8), 14-26. doi: 10.29121/granthaalayah.v9.i8.2021.4110 14 CONDUCTION DISORDERS AND PERMANENT CARDIAC PACEMAKER AFTER TRANSCATHETER AORTIC IMPLANTATION AN UPDATE OVERVIEW


INTRODUCTION
The most frequent valvular heart disease is aortic stenosis (AS). It involves 2%, 3% and 4% of elderly over 65, 75 and 85 years correspondingly, and the frequency appears to increase in intensity as the population ages Bajrangee A, Coughlan JJ, Teehan S, et al. 2017. It is an insidious disease with a long latency period, known to develop rapidly after the beginning of symptoms, heading to a high proportion of deaths in untreated patients Leon MB, Smith CR, Mack M, et al. 2010, Lemos PA, Mariani J, Esteves Filho A, et al. 2010, Junior ASM, de Oliveira PPC, Almeida LF, et al. 2018.

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Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement (SAVR) in patients with severe AS, who either cannot undergo surgery or are at intermediate/high surgical risk Yokoyama H, Tobaru T, Muto Y, et al. 2019, Kolkailah AA, Doukky R, Pelletier MP, Volgman AS, Kaneko T, Nabhan AF 2019, Popma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, et al. 2019.
Once a bioprosthetic valve is introduced through a catheter and installed within the injured natural aortic stenotic valve is a procedure named TAVI Leon MB, Smith CR, Mack M, et al. 2010. It is an option conventional surgery for patients with severe AS, who have an enhanced threat of surgery. It additionally increases patient survival and quality of life Monteiro C, Ferrari ADL, Caramori PRA, et al. 2017. Nowadays, despite this new technology, surgical valve replacement is the treatment of choice for symptomatic severe AS Lemos PA, Mariani J, Esteves Filho A, et al. 2010 andJunior ASM, de Oliveira PPC, Almeida LF, et al. 2018. There are more than a few valve models that can be implanted percutaneously at the aortic level; but most procedures in the literature use the "Edwards SAPIEN prosthetic heart valve" and the "CoreValve ReValving System" Piazza N, de Jaegere P, Schultz C, et al. 2008. The Edwards SAPIEN has a balloon inflatable stainless steel cylindrical rim to which is sewn a three-leaflet equine biological pericardial heart valve and a material skirt to attenuate paravalvular aortic regurgitation. The SAPIEN™ THV uses a stainless-steel frame and is available in two sizes: outer diameters of 23 and 26 mm and heights of 14.3 and 16.1 mm, respectively, when fully deployed. The newer SAPIEN XT™ THV is made of a cobalt-chrome frame; the strength of the alloy is greater and make available for a decrease in strut thickness with fewer stent struts, causing in a compliment device for introduction. As a result, radial strength may be lower. It is available in four sizes, with outer diameters of 20, 23, 26 and 29 mm and heights of 13.5, 14.3, 17.2 and 19.1 mm respectively Figure  1. It is expected that around one third of patients with the feature AS are postponed from surgical treatment since the high risk of postoperative mortality Lemos PA, Mariani J, Esteves Filho A, et al. 2010. TAVI is now "the standard of care for patients at high surgical risk or inoperable patients with severe AS," Bajrangee A, Coughlan JJ, Teehan S, et al. 2017 andJunior ASM, de Oliveira PPC, Almeida LF, et al. 2018. It allows percutaneous implantation of a novel aortic valve with standard procedures via the transfemoral approach under local anaesthesia, alternatively with transapical, transaortic and subclavian approaches -depending on the patient's vascular anatomy.
In general, these next-generation valves are self-expanding and have features that can facilitate valve positioning and improve annular sealing, as well as lower profile delivery systems to allow for smaller vessel diameters. These valves are currently in clinical trials, and it remains unclear whether outcomes will be inferior, comparable, or superior to current generation THVs Figure 2 Bajrangee A, Coughlan JJ, Teehan S, et al. 2017. TAVI is now "the standard of care for patients at high surgical risk or inoperable patients with severe AS," Bajrangee A, Coughlan JJ, Teehan S, et al. 2017. According to Sarmento-Leite R, De Quadros AS, Prates PRL, et al. 2009 the components of the cardiac conduction system, the valve ring and adjacent structures were compressed by the area near to the valve covered by the endoprosthesis. The atrioventricular node and the left branch of the His bundle pass within the fibrous body may be affected by the device because they are adjacent to the non-coronary cusp of the aortic valve Sarmento-Leite R, De Quadros AS, Prates PRL, et al. 2009, Perin MA, Sândoli de Brito F, Oliveira Almeida B, Pereira MAM, et al. 2009 Conduction defects and permanent pacemaker implantation (PPMI) remain a common and important consequence of transcatheter aortic valve replacement (TAVR). Understanding risk factors for TAVR-related conduction disorders could improve patient selection, procedural techniques and periprocedural efforts to monitor and treat heart block Tsoi M, Tandon K, Zimetbaum PJ, Frishman WH. 2021. Several studies have identified patient-related and procedural factors associated with new-onset left bundle branch block, high-grade atrioventricular block and the need for PPMI after TAVR. Notable patient-related predictors include pre-existing right bundle branch block, membranous septal length and calcification of the left ventricular outflow tract. Modifiable procedural predictors include device implantation depth, prosthesis oversize and valve type Monteiro C, Ferrari ADL, Caramori PRA, et al. 2017.
Although mortality and rates of serious problems have decreased with newer generation valves, rates of pacemaker implantation and conduction disturbances continue high with both self-expandable (SE) and balloon-expandable (BE) valves Thyregod HG, Steinbrüchel DA, Ihlemann N, et al. 2015

Eligibility criteria
A systematic literature search was conducted in PUBMED using "15 years" and "free full texts" as filters and with the keywords "TAVI", "TAVI AND pacing" and "TAVI AND complications" to identify eligible articles. There were no language restrictions. A total of 11 articles were carefully chosen from this search. To ensure background, consistency, and depth of text other databases such as SCIELO, Google Scholar and MEDLINE were used.

Inclusion and exclusion criteria
Articles that did not address complications occurring after TAVI placement and articles that centered on pre-existing genetic factors or diseases and aggravation of complications were rejected. This search may contain publication bias as it only reviews freely available articles. Therefore, it is necessary that additional studies are performed and related to those shown here Figure 3.

RESULTS AND DISCUSSIONS
The literature search firstly found 1648 significant titles from PUBMED, SCIELO, Google Scholar and MEDLINE. Of these, 1186 were removed due to duplicate entries. After reading the titles and abstracts, 20 articles were selected for full reading and 10 were included in the analysis. The study selection process and reasons for exclusion are reviewed in Figure 3.
Based on the analysis of the articles, it was possible to establish the most common complications after TAVI placement. Studies considered a possible association between TAVI and a decrease in coronary flow, which would lead to a myocardial injury reflected by a post-procedural increase in serum troponin I; however, no positive correlation with this finding could be established, as the existence of a reduction in blood pressure retrieval time was only seen in assessment to the duration of rapid pacing Kahlert P, Al-Rashid F, Plicht B, et al. 2016, Junior ASM, de Oliveira PPC, Almeida LF, et al. 2018.
A further complication was found in relation to the occurrence of new-onset and permanent LBBB after TAVI, which often required the implantation of a permanent pacemaker (PPM), but this did not increase the mortality rate of patients. The studies point to the need for careful and prolonged surveillance for the PPM indication during follow-up and to assess the impact of persistent LBBB on recent initiation ( Patients who had any of the above factors were 63% more likely to need PPM compared to 4% in patients who had none of these predictors. Ventricular atrial block (AV) has been found to be another conduction abnormality caused by TAVI placement and may be related to "...higher incidence of mortality, SCD and left ventricular dysfunction" as noted by Hamdan A, Guetta V, Klempfner R, et al. 2015. The same study also found that high-grade AV block occurred in 18% of patients analyzed in 1.2 ± 1.1 days after TAVI, with 29% undergoing PPM implantation in 2.2 ± 2.1 days Junior ASM, de Oliveira PPC, Almeida LF, et al. 2018. Lemos PA, Mariani J, Esteves Filho A, et al. 2010 was the only article to address the expansion of severe aortic regurgitation of the prosthetic valve 16 months after TAVI. To resolve the question, a CoreValve Evolut R prosthesis was implanted directly above the LV -edge of the JenaValve used. The treatment option applies to the transvalvar defect made explicit in the case.
To better understand what was found in the review, a table was created with the main articles used and their main points, such as title, year of publication, authors, journal and a preview of the conclusion and main points of the results Table 1. years. At 30 days, TAVR resulted in a lower rate of stroke (P = 0.02) and a lower rate of death or stroke (P = 0.01) and new-onset atrial fibrillation (P 0.001) than surgery. TAVR also resulted in a shorter index hospitalization than surgery (P 0.001) and a lower risk of poor treatment outcome (death or a low Kansas City Cardiomyopathy Questionnaire score) at 30 days (p<0.001). There were no significant differences between groups in serious vascular complications, new permanent pacemaker insertions or moderate or severe paravalvular regurgitation.
In patients with severe AS, who were at low surgical risk, the composite rate of death, stroke or rehospitalization at 1 year was significantly lower with TAVR than with surgery. After 8 years follow-up, the estimated risk for the composite outcome of all-cause mortality, stroke or myocardial infarction was 54.5% after TAVI and 54.8% after SAVR (P = 0.94). The estimated risks of all-cause mortality (51.8% vs 52.6%; P = 0.90), stroke (8.3% vs 9.1%; P = 0.90) or myocardial infarction (6.2% vs 3.8%; P = 0.33) were similar after TAVI and SAVR. The risk of structural valve deterioration was lower after TAVI than after SAVR (13.9% vs. 28.3%; P = 0.0017), while the risk of bioprosthetic valve failure was similar (8.7% vs. 10.5%; P = 0.61).
In patients with severe aortic valve stenosis at low surgical risk randomized to TAVI or SAVR, there were no significant differences in the risk of all-cause mortality, stroke or myocardial infarction, or in the risk of bioprosthetic valve failure after 8 years of follow-up. CFVR = coronary flow velocity reserve; AUC = area under the curve of TnI; HITS = high-intensity transient signals; MS = membranous septum.
According to Akin I, Kische S, Paranskaya L, et al. 2012, when considering the risk factors for complete AV block after surgical valve replacement, "prior aortic regurgitation, pulmonary hypertension, myocardial infarction, and postoperative electrolyte imbalance are the main risk factors. The strongest predictor of the need for a pacemaker is RBBB on surface ECG." In TAVI, the overall local impairment is influenced by factors such as calcification at the surgical site, height of the implantation site in the left ventricular outflow tract, intensity of the trauma that occurred during the procedure (balloon valvuloplasty, balloon to aortic annulus ratio and post-TAVI dilatation) and aortic annulus geometry. TAVI could be performed safely and effectively in nonagenarians with acceptable long-term outcomes compared to younger patients, although attention should be paid to major vascular complications as seen in Figure 4 by Yokoyama H, Tobaru T, Muto Y, et al. 2019.
In 2020, TAVI has been recognized as one of the most important revolutionary therapies in modern medicine due to the PARTNER3 Mack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK, et al. 2019 andEVOLUT LOW RISK Popma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, et al. 2019 clinical trials and is indicated for low-risk patients (STS 4%). The PARTNER3 trial, conducted in 71 centers with patients with a mean age of 73 years and an STS of 1.9%, showed superiority of TAVI for the primary composite endpoint (death, stroke and rehospitalization) at one-year follow-up. The secondary endpoints showed a lower incidence of new AF within 30 days, lower hospitalization rates and more effective control of heart failure-related symptoms (according to the KCCQ score and the 6-minute walk test).
The EVOLUT LOW RISK study, conducted in patients in the same age range, analyzed the composite endpoint of death and stroke at 24-month follow-up. The study showed a lower incidence of debilitating stroke, acute renal failure, bleedingrelated complications and atrial fibrillation. In contrast, the study showed a higher incidence of moderate to severe aortic regurgitation and an increased need for pacemaker implantation.
According to Kolkailah AA, Doukky R, Pelletier MP, Volgman AS, Kaneko T, Nabhan AF. 2019, three studies reported short-and long-term PPM implantation Popma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, et al. 2019, Mack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK, et al. 2019, Thyregod HG, Steinbrüchel DA, Ihlemann N, et al. 2015. TAVI probably increased the risk of short-term PPM, and this increased risk persisted in the long term (RR (random effects) = 3.48, 95% CI = 1.40 to 8.62; 2683 participants; 3 trials; Tau2 = 0.53; Chi2 = 15.78, df = 2 (P = 0.0004); I2 = 87%; NNTH = 6, 95% CI = 3 to 48; Analysis 1.17). However, there was observed heterogeneity despite confirmation of data accuracy and absence of 22 methodological error. Possible explanations for this heterogeneity may be differences in the populations or interventions of the studies. For example, the valve type used in the TAVI groups differed between studies, with NOTION 2015 Thyregod HG, Steinbrüchel DA, Ihlemann N, et al. 2015and EVOLUT 2019Popma JJ, Deeb GM, Yakubov SJ, Mumtaz M, Gada H, et al. 2019using SE valves, while PARTNER 3 2019Mack MJ, Leon MB, Thourani VH, Makkar R, Kodali SK, et al. 2019 In addition, the NOTION 2015 participants were older on average. We also noted the lower number of events in the surgical arm of NOTION 2015 compared with the other two studies; therefore, we used a random effects model for pooling outcomes. STACCATO 2012 reported 90-day PPM implantation, where two of the 34 participants in the TAVI group had an event, compared with one of the 36 in the SAVR group. NOTION 2015 reported longer-term follow-up for PPM implantation with persistent increased risk in TAVI recipients at two years (TAVI = 41.3% vs SAVR = 4.2%, log-rank P 0.001) and five years (TAVI = 41.7% vs SAVR = 7.8%, logrank P 0.001) Kolkailah AA, Doukky R, Pelletier MP, Volgman AS, Kaneko T, Nabhan AF. 2019.
After 8 years of follow-up Nordic Trial (NOTION 2015), left ventricular ejection fraction was similar between TAVI and SAVR patients and the risk of all-cause mortality was not significant, although numerically higher, in pacemaker-naïve patients who underwent permanent pacemaker implantation within 30 days of TAVI compared with patients without a permanent pacemaker. A lower threshold for prophylactic pacemaker implantation in the early TAVI period may have resulted in a low percentage of pacemakers, potentially attenuating the effects of pacemaker implantation. However, the percentages of pacemakers in the present study were not available to confirm this Jørgensen T H, Thyregod H G, Ihlemann N, et al., 2021, Serruys PW, Piazza N, Cribier A, et al. 2009, Yokoyama H, Tobaru T, Muto Y, et al. 2019.
The rate of more than mild PVL after TAVI was higher in the NOTION study than in current practices, which may be explained in part by the sizing of the aortic annulus, which was performed by echocardiography rather than computed tomography, and the use of primarily first-generation THV without an outer sealing skirt and the possibility of repositioning. Leon MB, Smith CR, Mack M, et al. 2010, Yokoyama H, Tobaru T, Muto Y, et al. 2019. The presence of PVL was not associated with an increased risk of mortality after 8 years of follow-up. Nevertheless, the risk of all-cause mortality was increased in TAVI patients with mild vs. no or trace PVL in the 5-year data from the PARTNER 1 trial (73.0% vs. 68.3%; P = 0.003) and the PARNTER 2 trial (48.7% vs. 41.1%; P= 0.07).6,8 This trend towards higher mortality in patients with PVL after TAVI may be concerning for younger patients with longer life expectancy Jørgensen T H, Thyregod H G, Ihlemann N, et al., 2021, Chen S, Chau KH, Nazif TM. 2020. "Representative studies were limited to those published after 2016 and with a sample size ≥ 100 (unless only smaller ones were available). KM Estimated event rates from 30-day PPM were presented where possible: (a) rates reported in this study from PPM were not separated by valve type; (b) reported rate is the proportion of patients with new PPM (not KM estimated); (c) patients with PPM or LBBB at baseline (depending on outcome of interest) were excluded. LBBB = left bundle branch block; PPM = permanent pacemaker; THV = transcatheter heart valve." Source: Chen S, Chau KH, Nazif TM. The incidence and impact of cardiac conduction disorders after transcatheter aortic valve replacement. Ann Cardiothorac Surg. 2020 Nov;9(6):452-467. doi: 10.21037/acs-2020-av-23.
Consequently, continuous follow-up of patients undergoing TAVI is required to identify potential complications and treat possible conduction disorders. However, studies with a much larger cohort of patients are needed to provide definitive data on the risk of delayed life-threatening arrhythmias and sudden death after TAVRespecially in those patients who have conduction disorders after the procedure. Indeed, these risk scores may need to consider the type of transcatheter valve (a risk score for each valve may be required). Importantly, the application of a consistent strategy regarding the management of conduction disturbances across multiple centers seems to be the key to establishing reliable arrhythmia risk scores, as seen in Figure 4.