Long-term Durability of TAVR Encouraging: NOTION, UK TAVI

Batya Swift Yasgur MA, LSW

February 13, 2019

Transcatheter aortic valve replacement (TAVR) shows long-term durability with less structural valve deterioration than surgical aortic valve replacement (SAVR), newly published findings of two studies suggest.

In the Nordic Aortic Valve Intervention (NOTION) trial, Søndergaard and colleagues compared 139 patients with severe aortic stenosis at low risk for mortality who were treated with TAVR with matched patients treated with SAVR.

At 6 years, the rates for all-cause mortality, bioprosthetic valve failure (BVF), and nonstructural valve deterioration (NSVD) were similar. The rate of structural valve deterioration (SVD) was higher for SAVR than for TAVR.

"In the NOTION trial through 6 years, structural valve deterioration was significantly greater for SAVR than for TAVR, whereas bioprosthetic valve failure was low and similar for both groups," lead author Lars Søndergaard MD, DMSc, professor of cardiology, the Heart Center, Rigshjospitalet, Copenhagen University Hospital, told theheart.org | Medscape Cardiology.

"As TAVR is expected to become a treatment option for patients with longer life expectancy, knowledge on the durability of transcatheter bioprosthetic valves is crucial," he said.

The second study conducted by Blackman and colleagues looked at the incidence of SVD 5 to 10 years after the procedure, using data from the United Kingdom Transcatheter Aortic Valve Implantation (UK TAVI) registry.

A total of 241 patients were evaluated at baseline and then re-evaluated 5 to 10 years later. Two-thirds of patients were treated with a self-expandable valve and the remainder were treated with a balloon-expandable valve.

Peak aortic valve gradient at follow-up was lower than it was immediately after the procedure. Additionally, more patients had nontrivial aortic regurgitation (AR) and fewer had mild AR at follow-up.

"The main finding was that evidence of structural valve degeneration was very rare. Only one case out of 241 had severe SVD, and 21 cases, which is only 8.7%, had moderate SVD," lead author Daniel Blackman, MBChB, MD, MRCP, interventional cardiologist, Leeds Teaching Hospitals NHS Trust, and clinical associate professor in medicine, University of Leeds, United Kingdom, told theheart.org | Medscape Cardiology.

"These data are very reassuring, suggesting that there is little evidence of significant SVD in patients [treated with TAVR], most of whom were evaluated at 5 to 6 years, which is the time frame in which you might expect the valve to start degenerating more," he said.

Both studies were published online February 4 in the Journal of the American College of Cardiology.

Longer Life Expectancy

TAVR "has provided a safe treatment option for many high- and extreme-risk patients" who, prior to 2007, were precluded from receiving SAVR, write Søndergaard et al.

Recent trials have "established the noninferiority of TAVR, compared to SAVR, in intermediate-risk patients," and findings have "led to the rapidly growing adoption of TAVR for treatment of severe, symptomatic aortic stenosis," they note.

However, TAVR is now being used for younger, lower-risk patients as well.

"As TAVR is expected to soon become a treatment option for patients with longer life expectancy, knowledge on the durability of transcatheter bioprosthetic aortic valves is crucial," Søndergaard said.

Previous studies of both SAVR and TAVR have used "dissimilar" definitions to investigate the durability of the implanted bioprosthesis, but "it is important to use standardized definitions," he emphasized.

To do so, the researchers used definitions from a consensus statement issued by the European Association of Percutaneous Cardiovascular Interventions (EAPCI), the European Society of Cardiology (ESC), and the European Association for Cardiothoracic Surgery (EACTS).

Moderate/severe SVD was defined as "a mean gradient ≥20 mm Hg, an increase in mean gradient ≥10 mm Hg from 3 months postprocedure, or more than mild intraprosthetic aortic regurgitation either new or worsening from 3 months postprocedure."

Nonstructural valve deterioration (NSVD) was defined as "moderate/severe patient–prosthesis mismatch at 3 months or moderate/severe paravalvular leakage."

BVF was defined as "valve-related death, aortic valve reintervention, or severe hemodynamic SVD."

Using consistent definitions of durability enabled more accurate comparison and study of patients with longer life expectancy, Søndergaard said.

"Since the NOTION trial was the first to include patients at low surgical risk, the trial opens for evaluation of these important questions," he added.

NOTION was a prospective, randomized, unblinded clinical trial conducted at three centers in Denmark and Sweden. Patients were enrolled from December 2009 to April 2013.

Patients 70 years and older with severe aortic stenosis were randomized 1:1 to SAVR (n = 135) or TAVR with CoreValve (Medtronic; n = 139) and received annual echocardiographic assessments.

"Encouraging" Findings

Follow-up was complete through 5 years, with both groups showing 100% compliance.

At 6 years, the rates of all-cause mortality were shown to be similar for TAVR and SAVR patients (42.5% vs 37.7%; P = .58).

Moreover, forward-flow hemodynamics remained consistent throughout the 6 years and the effective orifice area was significantly greater for TAVR than for SAVR at all postprocedure time points.

No differences were shown between TAVR and SAVR patients for BVD (56.1% vs 66.7%; = .07), NSVD (54.0% vs 57.8%; P = .52), or endocarditis (5.8% vs 5.9%; P = .95).

Likewise, BVF rates after TAVR and SAVR remained similar through 6 years (7.5% vs 6.7%; P = .89), with no statistically significant differences in the frequency of the components of BVF between TAVR and SAVR groups (i.e., in valve-related deaths, reintervention, and severe hemodynamic SVD).

By contrast, the rate of SVD was significantly higher for SAVR than for TAVR (24.0% vs 4.8%; < .001), which was primarily related to differences in measures of moderate hemodynamic SVD.

"Although follow-up is medium-term, the low rates of SVD and BVF after implantation of the expanding CoreValve bioprosthesis are encouraging," the authors conclude.

"Longer-term follow-up of randomized clinical trials will be necessary to confirm these findings before adapting TAVR routinely in patients with longer life expectancy," Søndergaard said.

Deterioration Infrequent

"Assessments of valve function in the early randomized trial cohorts and registries have consistently shown preserved valve function up to 5 years after TAVR," write Blackman and colleagues.

However, SVD after SAVR is usually not seen until 5 to 10 years after the procedure, and data in this time frame after TAVR are very sparse.

"There is a pressing need for greater understanding of the long-term durability of TAVR valves, particularly as TAVR moves into lower-risk cohorts," they state.

To investigate the question, the researchers used data from the UK TAVI registry, a prospective mandatory database that includes all patients undergoing TAVR in the United Kingdom.

The current study utilized de-identified demographic, procedural, and in-hospital outcome data on all patients who underwent TAVR in the United Kingdom from 2007 to 2011.

Baseline echocardiographic data were obtained from the first transthoracic echocardiogram performed after the TAVR procedure (no more than 6 months after valve implantation), whereas follow-up echocardiographic data were derived from the most recent transthoracic echocardiogram (no less than 4 years 6 months after TAVR).

Echocardiographic data both at baseline and at least 4.5 years after TAVR were available for 241 patients, who formed the study population (53.6% were male; mean age was 79.3 ± 7.5 years, mean logistic EuroSCORE was 19.7% [95% CI, 18.4% - 21.6%]).

TAVR was performed for treatment of pure aortic stenosis or degeneration of a surgical valve in 91.4% and 6.8% of patients, respectively.

Of the patients, 64% were treated with the self-expandable CoreValve system, 34.3% with a balloon-expandable Sapien/Sapien XT valve (Edwards), and 1.7% with Portico (Abbott Vascular).

The median echocardiographic follow-up was 5.8 years (interquartile range, 5.3 to 7.7 years), with follow-up extending to 6 years (69%), 7 years (28%), 8 years (12%), 9 years (4%), and 10 years (1%).

At follow-up, the peak aortic valve gradient was lower than it had been after the procedure (17.1 vs 19.1 mm Hg, P = .002).

In addition, more patients had none/trivial AR (47.5% vs 33.0%), and fewer had mild AR (42.5% vs 57.0%, = .02).

The researchers identified only one case (0.4%) of severe SVD 5.3 years after implantation (new severe AR).

In contrast, there were 21 cases (8.7%) of moderate SVD (mean, 6.1 years after implantation; range, 4.9 to 8.6 years) related to new AR (57%) or restenosis (43%).

"Our main purpose was to look at structural valve degeneration [in patients who had undergone TAVR], and we found it very infrequent in that time frame, with excellent long-term aortic valve function," Blackman reported.

"In patients with the self-expanding valve, we found improvement in paravalvular leaks and paravalvular aortic regurgitation," he said.

Although both the self-expandable and the balloon-expandable prostheses were found to be durable, the self-expandable device was associated with some reduction in peak gradient over time, he noted.

However, it also showed improvement in paravalvular AR, with a significant increase in the number of patients who showed either no leak or only a trivial leak.

"This might be because the device might continue expanding over time, resulting in a leak reduction, instead of already being fully expanded, as in the balloon-expansion device," he suggested.

The Countdown Is On

In an accompanying editorial, Patrizio Lancellotti, MD, PhD, and colleagues, University of Liège Hospital, GIGA Cardiovascular Sciences, Departments of Cardiology and Cardiovascular Surgery, Heart Valve Clinic, Belgium, write that "in the real world, the countdown has already started for extending the use of TAVR to patients at low surgical risk."

They call the data from these trials "very reassuring," but emphasize that "further long-term studies are warranted, particularly with respect to the desire to extend the indications of TAVR to young, low-risk patients."

They conclude that, in light of the experience with surgical SVD (which is usually not seen until 5 to 10 years after the procedure) and the inverse relation between age at SAVR and subsequent SVD, "more time would be needed to accurately assess long-term valve durability and to understand the mechanism of potential BVF, which, in turn, will enable us to devise preventive strategies."

Blackman added that findings of two major trials of TAVR in low-risk patients will be presented at the upcoming annual meeting of the American College of Cardiology (ACC) in March.

"When clinicians are looking at TAVR in younger patients between ages 65 and 75, the most important fact will be the durability of the valve; and if it is found durable, this will provide encouragement to clinicians treating these younger patients," he said.

The study by Blackman et al was supported by the National Institute for Health Research (NIHR) infrastructure at Leeds . Blackman has been a consultant and proctor for Medtronic and Boston Scientific. The other authors' disclosures are listed on the original paper. The study by Søndergaard et al was supported by the Danish Heart Foundation and Medtronic. Søndergaard has received consultant fees and institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and Symetis. The other authors' disclosures are listed on the original paper. Lancellotti and coauthors report no conflicting interests.

J Am Coll Cardiol. Published online February 4, 2019. Blackman abstract, Søndergaard abstract, Editorial

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