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A new formula that uses hemodynamic measurements to assess aortic regurgitation during transcatheter aortic valve replacement (TAVR) can better predict 1-year mortality than echocardiography alone, according to data published in the March 27, 2012, issue of the Journal of the American College of Cardiology. By providing point-of-care feedback, it may also enable clinicians to minimize the degree of periprocedural regurgitation.

For the prospective study, investigators led by Georg Nickenig, MD, of Rheinische Friedrich-Wilhelms-Universität Bonn (Bonn, Germany), looked at 146 high-surgical-risk patients (mean logistic EuroScore 30.2 ± 18.0%) with severe aortic stenosis who underwent TAVR with the third-generation CoreValve prosthesis (Medtronic, Minneapolis, MN).

Echocardiographic assessments performed up to 3 days following TAVR showed that the vast majority of patients had no (36.3%) or only mild (48.6%) periprosthetic aortic regurgitation, whereas 15% had moderate (12.3%) or severe (2.7%) regurgitation.

Adding a Hemodynamic Metric

The researchers developed a hemodynamic measure called the aortic regurgitation index, calculated as the ratio of the gradient between diastolic blood pressure and left ventricular end-diastolic pressure to systolic pressure. As the severity of aortic regurgitation increased, index values decreased proportionally (P < 0.001 for trend):

• None = 31.7 ± 10.4
• Mild = 28.0 ± 8.5 (P = 0.04 vs. none)
• Moderate = 19.6 ± 7.6 (P < 0.01 vs. mild)
• Severe = 7.6 ± 2.6 (P = 0.006 vs. moderate)

Overall, 6.8% of patients died within 30 days and 26.7% died within 1 year. Echocardiographic regurgitation severity was associated with mortality at both time points (P = 0.001 and P < 0.001, respectively), such that 1-year mortality (the primary endpoint) occurred in threefold more patients with moderate/severe regurgitation than in those with no/mild regurgitation (63.6% vs. 20.2%; P < 0.001).

On multivariate analysis, echocardiographic moderate/severe regurgitation predicted 1-year mortality (HR 2.4; 95% CI 1.0-5.4; P < 0.042). So did an aortic regurgitation index of less than 25 (the cutoff value determined by receiver-operating characteristic analysis)—even after adjustment for the severity of aortic regurgitation (HR 2.9; 95% CI 1.3-6.4; P = 0.009). In particular, patients with an index measure less than 25 had a 46.0% risk of dying within 1 year compared with a 16.7% risk for those who had a higher index value (P < 0.001).

Mortality Prediction Enhanced

Across the spectrum of severity, the ability of echocardiographic regurgitation to predict 1-year mortality was refined by factoring in hemodynamic measurements (P < 0.001).

In patients with no/mild regurgitation, a regurgitation index of at least 25 was associated with a 15.4% mortality rate, while an index below the cutoff was associated with a 33% mortality rate. Patients with moderate/severe aortic regurgitation and an index of less than 25 fared worst, with a 1-year mortality of 70.6%.

The message of these findings, Dr. Nickenig and colleagues write, is that “all measures must be taken to avoid moderate/severe [periprosthetic aortic regurgitation]”—and that such efforts may in the end increase survival.

They caution, however, that the regurgitation index varies with the level of the left ventricular end-diastolic pressure, which may be elevated due to a variety of factors. This could lead, in turn, to ‘false positives,’ underscoring the value of combining the index with imaging assessments. Indeed, the regurgitation index displays its strongest discriminative ability in patients with borderline significant regurgitation.

The authors conclude that their data provide a “simple-to-assess, investigator-independent, and immediately performed parameter, which can be used to guide periprocedural clinical decisions in [TAVR] patients.”

Not Just Severity but Tolerability 

In a telephone interview with TCTMD, Philippe Genereux, MD, of Columbia University Medical Center (New York, NY), said the index provides a simple way to assess not just the severity of regurgitation but its tolerability—ie, whether it will have a clinical impact.

Dr. Genereux noted that for every category of regurgitation, a patient with elevated left ventricular end diastolic blood pressure—and thus a low index—is at higher risk. Even for patients with no or mild regurgitation, 1-year mortality increases from 15% to 33% if the index is below the cutpoint, he pointed out, adding that perhaps the cutoff should be even higher, to encompass a lower grade of regurgitation.

A potential drawback of the new metric is that a heart failure patient with very high left ventricular end diastolic blood pressure will have a low regurgitation index, Dr. Genereux and the study authors note. Therefore, it can be difficult to dissociate the mortality risk of heart failure from that associated with regurgitation.

Currently, operators rely on real-time imaging, which is technically challenging, to assess and try to resolve moderate or severe regurgitation—perhaps by postdilation or implantation of another valve. But clinicians may now view even a patient with mild regurgitation as being at higher risk, Dr. Genereux observed.

Nonetheless, trying to determine whether regurgitation in such patients will respond to procedural modifications will be a challenge, especially if heart failure is an underlying problem, he said, noting that “you have to weigh the risk vs. the benefit of a more aggressive strategy.”

Still, “this is a good first step,” Dr. Genereux concluded, predicting that these data may motivate researchers to focus more attention to regurgitation among TAVR complications.

He added that clinicians are likely to be less interested in the index itself, which may be a bit simplistic and requires validation, than the concept behind it—that the clinical importance of regurgitation depends as much on its hemodynamic background as on its severity.

Study Details

The degree of periprosthetic aortic regurgitation and clinical outcomes were all defined according to VARC criteria.

Compared with patients who had no or mild regurgitation, those who had moderate or severe periprosthetic regurgitation were more often male (77.3% vs. 42.7%; P = 0.003) and taller (173.8 cm vs. 166.0 cm; P < 0.001). In addition, their mean aortic annulus diameter was larger (25.1 mm vs. 23.2 mm; P < 0.001).

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• CoreValve Trial Results Promising

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