A point-of-care test for abnormalities in the clotting protein von Willebrand factor may predict paravalvular regurgitation and outcomes after transcatheter aortic valve replacement (TAVR), a study shows.
Femoral blood samples collected before the TAVR procedure showed that clotting factor had been unfolded by turbulent blood flow through the paravalvular leak, generating a lower ratio of high-molecular-weight multimers (HMW) than normal.
The ratio normalized after TAVR in patients without aortic regurgitation and in cases where aortic regurgitation was successfully treated by balloon dilation during the procedure, Sophie Susen, MD, PhD, of Institut Pasteur de Lille in France, and colleagues reported in the July 28 issue of the New England Journal of Medicine.
However, levels did not rebound in patients with persistent aortic regurgitation, as confirmed by transesophageal echocardiography (TEE).
A point-of-care test for those hemostatic irregularities — 180 seconds or greater closure time with adenosine diphosphate (CT-ADP) at the end of TAVR measured on the Platelet Function Analyzer 100 device — predicted aortic regurgitation with an area under the curve of 0.93 (95% CI 0.87 to 0.98) and sensitivity, specificity, and negative predictive values of 92.3%, 92.4%, and 98.6%, respectively.
The test was linked to outcomes as well. Those who crossed the CT-ADP threshold of 180 seconds had a 1-year survival rate after TAVR of 41.7% versus 12.2% (P<0.001).
“These findings suggest that measurement of CT-ADP, which can be performed as a point-of-care test, could be used for monitoring during TAVR procedures to identify a subgroup of patients for whom TEE or other imaging methods may be appropriate,” the authors concluded.
CT-ADP may have a role especially in the expansion of the procedure, according to Firas E. Zahr, MD, and Steven R. Lentz, MD, PhD, both of University of Iowa Carver College of Medicine in Iowa City.
“With the development of newer TAVR devices and the extension of the indications to include lower-risk patients, increasing numbers of TAVR procedures are likely to be performed with the patient under conscious sedation rather than general anesthesia, and without the routine use of TEE.”
“In this clinical setting, a sensitive point-of-care test to detect paravalvular regurgitation could potentially aid in the identification of patients who need an additional intervention,” Zahr and Lentz wrote in an accompanying editorial.
The CT-ADP is a promising candidate for routine testing during TAVR, they suggested, citing the high negative predictive value in both the primary and validation cohorts. Nonetheless, these were mainly patients with severe aortic stenosis, a high transaortic gradient, and a normal ejection fraction, they commented, urging that “caution must be taken” in extrapolating these results to other patients.
“As indications for TAVR expand, more data will be needed to define the value for the CT-ADP and other point-of-care tests of von Willebrand factor function in lower-risk patients who are more likely to undergo TAVR without TEE guidance. Such patients are likely to be the ones who would benefit the most from rapid, noninvasive testing for the presence of paravalvular regurgitation.”
“Finally, it still remains unclear whether post-TAVR paravalvular regurgitation is predictive of an increased risk of death at 1 year because of adverse effects of residual high shear stress (e.g., chronic hemolysis and bleeding) or simply because it is a marker of other clinical risk factors,” according to the editorialists.
Susen’s study enrolled 183 patients who underwent TAVR with the Sapien XT between 2012 and 2014 at a single center. TEE identified those with aortic regurgitation (n=46), who underwent subsequent balloon dilation.
Another cohort of 201 was analyzed for validation of the hemostasis assessment. Patients came from multiple institutions and received the Sapien XT, Sapien 3, or CoreValve.
Persistent aortic regurgitation confirmed with TEE was predicted by abnormal HMW measurements (area under the curve 0.94, 95% CI 0.89 to 0.99). The optimal threshold for discriminating potential regurgitation was a ratio of 0.80 for the amount of the largest multimers in the sample compared with the amount in normal pooled human plasma; this model boasted sensitivity, specificity, and negative predictive values of 92.3%, 94.9%, 98.7%, respectively.
Patients with an HMW-multimer ratio of 0.8 or more at the end of TAVR were more likely to die a year later (40.6% versus 13.2% for lower scorers, P<0.001).
The investigators acknowledged that their single-center study had a small sample size. Additionally, they failed to account for the use of clopidogrel (Plavix) or other drugs.
The study was supported by Lille 2 University and Lille University Hospital.
Susen declared no relevant conflicts of interest.
Zahr disclosed serving as a site sub-investigator for the PARTNER 2 trial.
Lentz reported receiving research grants and consulting fees from Novo Nordisk and owning equity in Celgene.
New England Journal of Medicine
Van Belle E, et al “Von Willebrand factor multimers during transcatheter aortic-valve replacement” N Engl J Med 2016; DOI: 10.1056/NEJMoa1505643.
New England Journal of Medicine
Zahr FE, Lentz ST “Von Willebrand factor — a rapid sensor of paravalvular regurgitation during TAVR?” N Engl J Med 2016; DOI: 10.1056/NEJMe1607326.