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Moderate or severe aortic regurgitation develops in more than 1 in 10 patients who undergo transcatheter aortic valve replacement (TAVR) and appears to double mortality at 1 year, according to a large meta-analysis published in the April 16, 2013, issue of the Journal of the American College of Cardiology. Though the prognostic impact of mild regurgitation—the far more common form of the complication—is less clear, every effort should be made to minimize the complication, the authors say.

Investigators led by Samir R. Kapadia, MD, of the Cleveland Clinic (Cleveland, OH), reviewed 45 papers (2 randomized comparisons and 43 observational studies) published between 2008 and 2012 including 12,926 TAVR patients. Transfemoral or subclavian access was used in 65.1% of cases and a transapical or aortic approach in 30.9%. The self-expanding CoreValve device (Medtronic, Minneapolis, MN) was implanted in 40.7% and the balloon-expandable Sapien valve (Edwards Lifesciences, Irvine, CA) in 56.3%.

Moderate/Severe Regurgitation Higher with CoreValve

The pooled estimate for the overall incidence of moderate or severe aortic regurgitation, the primary endpoint, was 11.7% (95% CI 9.6-14.1%). Regurgitation at this level of severity was more common after CoreValve implantation (16.0%; 95% CI 13.4-19.0%) than Sapien implantation (9.1%; 95% CI 6.2-13.1%; P = 0.005).

The incidence of regurgitation was inversely proportional to the degree of severity. About one-third of patients showed no sign of the complication (table 1).

Table 1. Incidence of Aortic Regurgitation by Severity

Three predictors of regurgitation emerged from 25 studies:

• Prosthetic valve undersizing
• Improper implantation depth
• Aortic valve calcification

Of these, only the CT-derived mean Agatston calcium score clearly correlated with development of moderate or severe regurgitation (pooled estimate r = 0.47; 95% CI 0.30-0.61; P = 0.001).

Moderate or severe regurgitation was associated with increased mortality at both 30 days (OR 2.95; 95% CI 1.73-5.02) and 1 year (HR 2.27; 95% CI 1.84-2.81; both P = 0.001). Mild regurgitation was also linked to higher mortality (HR 1.829; 95% CI 1.005-3.329) in 5 studies involving 1,620 patients. However, when 3 of the trials were removed in a sensitivity analysis, only a trend toward increased mortality remained.

‘Mild’ in Name Only

In a telephone interview with TCTMD, Peter C. Block, MD, of Emory University School of Medicine (Atlanta, GA), said that the pooled data on the incidence and clinical relevance of moderate and severe regurgitation are nothing new. “But what I found interesting is that even mild regurgitation had a mortality effect,” he observed. “Although the effect disappeared in the sensitivity analysis, it did pop up as something that has to be looked at.”

Philippe Généreux, MD, of Columbia University Medical Center (New York, NY), agreed, noting that data from the PARTNER trials had already suggested that mild regurgitation might also carry a poor prognosis.

“The problem is that ‘mild’ is very difficult to define,” he told TCTMD in an interview, noting that imaging techniques and grading schemes for categorizing regurgitation severity have yet to be standardized and validated. Moreover, the degree of regurgitation tends to be underestimated, he added.

In fact, a major limitation of the meta-analysis is that only 1 of the trials included—PARTNER—used an echocardiographic core lab to determine regurgitation severity, Dr. Généreux observed. Data reported from other studies are subjective, he said, and “any conclusion based on these classifications should be taken very cautiously because we’re comparing apples and oranges.”

All in the Timing

Another source of uncertainty, Dr. Généreux noted, relates to the different times at which regurgitation was evaluated in the various studies—anywhere from right after the procedure up to 30 days. That makes a difference, he said, because with the Edwards valve there can be spontaneous regression of regurgitation over time. Dr. Block made a similar point about CoreValve, noting that the struts continue to expand over 36 hours.

The optimal time to evaluate regurgitation is important and currently unknown, Dr. Block said. “Overall what we need is a large-scale evaluation of aortic regurgitation and its impact on outcomes that includes an agreed-upon quantitative analysis of aortic regurgitation when it is measured after TAVR. Then we can begin to make some reasonable comparisons,” he added.

None of the predictors of regurgitation identified here will come as a surprise to physicians in the TAVR field, Dr. Block said. He and Dr. Généreux agreed with the authors that 3-D echocardiography and CT can provide more accurate sizing of the annulus to help reduce valve-annulus mismatch. Dr. Block noted that at Emory, operators favor balloon sizing, although he admitted that that practice makes them “lone wolves.”

Severe calcification, another regurgitation predictor, is more difficult to deal with, Dr. Généreux noted. “You can postdilate, but some evidence suggests that that increases the risk of stroke, so there is a trade-off,” he commented.

Overall, operators should be aggressive in trying to minimize paravalvular leak and aortic regurgitation, Dr. Généreux said, but the methods used “are pretty primitive.” Even when TAVR is performed by highly experienced operators using optimal imaging modalities, it is likely to result in a significant amount of regurgitation, he observed.

Improved Devices Crucial to Solution

Dr. Block had a similar message. “Aortic regurgitation after TAVR is serious business,” he said. “I agree that everything should be done before the procedure to ensure appropriate valve sizing and then to deploy the valve carefully so that any leak is minimal. But in many cases that simply cannot be achieved.”

This is understandable, Dr. Block said, because TAVR in the United States is performed using first-generation devices. “They do a reasonable job, but they are not perfect,” he observed. “We have to rely on the next-generation valves to solve this problem with better design and better engineering. If they cannot, then TAVR has a serious Achilles’ heel.”

Until TAVR can substantially reduce the incidence of regurgitation, it cannot move into younger, lower-risk patients, Dr. Généreux added. “But I’m pretty confident that the new devices will address this issue,” he said.

 

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Source:
Athappan G, Patvardhan E, Tuzcu EM, et al. Incidence, predictors, and outcomes of aortic regurgitation after transcatheter aortic valve replacement: Meta-analysis and systematic review of literature. J Am Coll Cardiol. 2013;61:1585-1595.

 

 

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