Abstract
The NOTION trial, in this 10-year follow-up report, comprehensively compares transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in low-risk patients. The study reveals similar outcomes in terms of mortality, stroke, and myocardial infarction. TAVR demonstrates advantages such as improved effective orifice area and transprosthetic gradients, along with reduced rates of new-onset atrial fibrillation. However, it is associated with higher rates of permanent pacemaker implantation and paravalvular leaks. Concerns exist regarding the generalizability of findings and unblinding during outcome assessments.
Keywords: NOTION, TAVR, SAVR
Previous trials comparing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in low-risk patients showed that TAVR was non-inferior to SAVR at 2 years [1, 2]. However, concerns were raised on the longer-term outcomes of TAVR. Having published the 1-year and 5-year results [3, 4] of the Nordic Aortic Valve Intervention Trial (NOTION), the authors have now reported the 10-year follow-up data comparing TAVR and SAVR among low-surgical-risk patients [5].
Trial design
The NOTION trial was an investigator-initiated, multicenter, randomized, and nonblinded superiority trial, conducted at two centers in Denmark and one in Sweden. Patients older than 70 years of age with severe symptomatic aortic stenosis with a minimum life expectancy of 1-year were included in the study. Any patient with a second valve issue or a coronary lesion was excluded. Participants assigned to TAVR underwent implantation with the core-valve self-expanding bioprosthesis (Medtronic Inc., Minneapolis, MN). Patients undergoing SAVR received a bioprosthesis, and the choice of the valve type was left to the discretion of the surgeons. Primary outcome was the composite of death from any cause, stroke, or myocardial infarction (MI) at 1-year. Secondary outcome included functional measures like New York Heart Association (NYHA) class and echocardiographic parameters like paravalvular leak (PVL).
Trial findings
In the study, 1576 patients were screened, and 1296 patients were excluded with the remaining 280 patients randomized into TAVR (n = 145) and SAVR (n = 135). Of the patients excluded from the study 79% was because of not meeting the inclusion criteria. Cross over rates were low (1 in each group).
There was no difference between TAVR and SAVR with respect to the primary outcome (65.5% vs. 65.5% respectively, p = 0.90). There was also no difference between the two groups in terms of all-cause mortality (62.7% vs. 64.0% respectively, p = 0.80); stroke (9.7% vs. 16.4% respectively, p = 0.90) or MI (11% vs. 8.2% respectively, p = 0.40). The risk of new onset atrial fibrillation was significantly higher with SAVR (74.1% in SAVR versus 52% in TAVR, p < 0.01) while the need for permanent pacemaker implantation (PPI) was significantly higher with TAVR (44.7% TAVR vs 14.0% SAVR, p < 0.01). Functional NYHA class was similar between the groups (NYHA classes I and II, TAVR 83.7% and SAVR 80.6%, p = 0.93).
Echocardiographic outcomes
The effective orifice area and trans prosthetic gradient were significantly better with TAVR while the incidence of paravalvular leak with TAVR was 25.4% compared to 2.5% with SAVR (p < 0.01). None of the SAVR patients had moderate to severe paravalvular leak at 10-years which was observed in 4.3% cases of TAVR.
Bioprosthetic durability
The risk of structural valve deterioration (TAVR 15.4%, SAVR 20.8%, p = 0.3) and bioprosthetic valve failure (9.7% TAVR, 13.8% SAVR, p = 0.4) were similar between the groups. There was also no difference between the groups in terms of re-interventions (4.3% TAVR, 2.2% SAVR, p = 0.3).
Strengths of the NOTION trial
-
(i)
This is the first study to report a 10-year follow-up for patients at low surgical risk who were randomly assigned to either TAVR or SAVR.
-
(ii)
The study provided comprehensive assessment of clinical and echocardiographic outcomes.
Weaknesses of the NOTION trial
-
(i)
Approximately 80% of the individuals assessed did not meet the criteria for randomization, which raises concerns about the generalizability of the study population to real-world situations.
-
(ii)
Patients with bicuspid aortic valves and coronary artery disease were excluded from the trial.
-
(iii)
Relatively small sample size.
-
(iv)
Outcome assessments were conducted without blinding by the site itself.
-
(v)
Ninety percent of the valves used were porcine aortic valves.
Comment
The key message from the NOTION trial is that there were no significant differences between TAVR and SAVR with respect to all-cause mortality, stroke, or myocardial infarction after a 10-year follow-up. Re-intervention on the valves for structural valve degeneration or bioprosthetic valve failure was also similar. While TAVR resulted in larger effective orifice area and lower trans prosthetic gradients, this came at a price of increased PPI with TAVR. The requirement for PPI was more than three times higher with TAVR at 10 years [5], five times higher at 5 years [4], and more than 20 times higher compared to SAVR at 30 days after the procedure [3]. More than one-third of patients undergoing TAVR required PPI within 30 days of the procedure with TAVR [3]. This is in keeping with the low-risk EVOLUT [1] trial but in stark contrast to the Placement of Aortic Transcatheter Valves (PARTNER) trial 3 trial reports [2, 6].
Paravalvular leak was significantly more common with TAVR at all time points in the NOTION trial. However, the presence of PVL at the 3-month mark did not exhibit any discernible correlation with all-cause mortality over the subsequent 10 years. This stands in contrast to prior reports in the literature and a comprehensive meta-analysis encompassing 38 studies, and involving over 25,000 patients undergoing TAVR has demonstrated that PVL, regardless of its severity, is associated with diminished overall survival and increased rates of re-hospitalization. While, moderate to severe PVL has been identified as a more potent contributor to adverse outcomes, even mild PVL was found to be associated with increased adverse events, a relationship that appears to amplify with prolonged follow-up duration[7]. Similarly, another meta-analysis including 21,666 patients from 20 studies confirmed that the need for PPI following TAVR was also associated with increased all-cause mortality [8].
Thus, while SAVR was associated with an increased incidence of new-onset atrial fibrillation and higher trans-prosthetic gradients, these did not manifest in increased mortality at any observed time point. Equally, the increase in PVL as well as the need for PPI with TAVR also did not exert a discernible impact on survival. However, there are two important points which need to be stressed in this context. Firstly, the mean age of the patients in the NOTION trial was 79 years, and secondly, to be included in the study, the life expectancy needed to be only 1 year. In low-surgical-risk patients with longer life expectancy, SAVR has shown superior survival compared to age- and gender-matched counterparts, whereas TAVR results in lower long-term survival than the general population [9]. Thus, the lack of difference in mortality in elderly patients with shorter life expectancy cannot be extrapolated to younger “low-risk” patients. An alarming contextual consideration is the Society of Thoracic Surgeons’ report indicating that over 50% of patients under the age of 60 in the USA currently undergo TAVR with a sevenfold increase in mortality (TAVR 14%, SAVR 2%) at 5 years [10].
In conclusion, the NOTION trial offers a 10-year follow-up on TAVR and SAVR in low-risk patients. Both interventions demonstrate comparable outcomes in all-cause mortality, stroke, and myocardial infarction; however, the study’s nuances unveil distinctive trade-offs, notably a higher incidence of paravalvular leak and permanent pacemaker implantation with TAVR. Decision-making should transcend mere notions, recognizing the crucial nuances that shape informed choices, thereby ensuring optimal patient care.
Funding
None.
Data availability
Data used in the review is freely available.
Declarations
Ethical approval
Not applicable as a review article.
Consent to participate
Not applicable as a review article.
Conflict of interest
None.
Footnotes
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Data Availability Statement
Data used in the review is freely available.