Blood Test May Be Useful for Detecting Aortic Regurgitation During TAVR
A screening tool for identifying hemodynamic changes indicative of paravalvular regurgitation may allow for faster recognition and treatment of the leaks during TAVR, a French study shows.
Senior author Sophie Susen MD, PhD (Centre Hospitalier Régional, Lille, France), told TCTMD in an interview that measuring blood flow abnormalities in real time represents a “new concept” that could further streamline the field of minimalist TAVR.
“If you perform the test and the [TAVR] procedure is a success, the patient can go back to his room with no need to perform transesophageal echocardiography under general anesthesia,” she said, adding that use of the screening tool adds virtually no additional time to the procedure once the team has had some training in reading the results of the blood test.
“It’s rather simple to perform this test. The results are available within minutes after taking a little sample of blood and then you can determine whether you go to general anesthesia and do the echocardiography to evaluate the positioning of the valve,” Susen commented. “We believe use of this test will shorten the procedure time for many people while keeping the same high level of evaluation of outcomes.”
Paravalvular regurgitation has been increasingly associated with poor survival after TAVR. While improvements in valve design and technique have reduced rates of regurgitation, it remains a persistent procedural complication virtually never seen with surgical AVR.
The blood test measures closure time with adenosine diphosphate (CT-ADP), which is assessed by a platelet function analyzer that detects the ability of ADP-activated platelets to adhere to collagen under shear stress. According to Susen and colleagues, patients with severe aortic stenosis have been shown in prior studies to have a loss of high-molecular-weight multimers of von Willebrand factor. CT-ADP is highly sensitive to these multimer defects.
Correcting Regurgitation in Real Time
Published online July 27, 2016, ahead of print in the New England Journal of Medicine, the 183-patient, single-center study focused on use of the SAPIEN XT device (Edwards Lifesciences) in the setting of femoral TAVR. A baseline blood sample was drawn for the entire cohort and transesophageal echocardiography (TEE) was performed. TEE was repeated after the additional dilation or implantation, or approximately 15 minutes after valve implantation if no corrective procedure was performed, with final TEE done at the completion of the TAVR procedure. Additionally, blood samples were repeated 5 minutes after valve implantation and several more times during the procedure.
Overall, 46 patients experienced more than mild aortic regurgitation on TEE and received additional dilation with the same or larger balloon or were given a different device. Correction of regurgitation was successful in 20 of these patients, with 85.8% of the entire cohort having no aortic regurgitation on final TEE.
Among patients who did not have regurgitation, multimer ratios of von Willebrand factor as assessed by the rapid CT-ADP test increased from baseline to shortly after TAVR implantation, while the group with regurgitation did not see an increase in the ratio until after the correction with additional balloon dilation or second device implantation. Among the approximately 14% of patients in whom regurgitation persisted after TAVR, the ratio remained relatively low throughout the procedure and did not continually increase.
Overall, changes in multimer ratio for the entire cohort had a sensitivity, specificity, and negative predictive value of 92.3%, 94.9%, and 98.7%, respectively, for the ability to detect regurgitation. A separate validation cohort of 201 patients from multiple institutions who underwent TAVR with different valves confirmed the predictive ability of the CT-ADP test.
According to Susen and colleagues, the final CT-ADP and the final multimer ratio are better predictors of 1-year mortality than TEE. “This suggests that flow-related biologic markers provide an integrated assessment of valve function that is distinct from, and perhaps more accurate than, the assessment obtained with imaging,” they write.
Over 1-year follow-up, the rate of mortality was more than doubled in those with versus without regurgitation at the end of the procedure (34.6% vs 15.3%; P = 0.02).
Susen told TCTMD that while this screening method is being used currently in her institution for TAVR, a larger, multicenter trial is now needed. “Our trial wasn’t designed to assess the results in patients receiving clopidogrel loading dose, so that is something to consider,” she noted.
Blood Tests for All TAVR Patients?
In an editorial accompanying the study, Firas E. Zahr, MD, and Steven R. Lentz, MD, PhD (both University of Iowa Carver College of Medicine, Iowa City, IA), question whether von Willebrand factor testing should be routinely used during TAVR. They suggest caution in extrapolating the findings to broader groups of patients, such as those with a low gradient or a low ejection fraction, and those receiving smaller TAVR valves with higher residual transvalvular aortic gradients.
But the findings are timely in light of expanding indications for TAVR, they note, adding that “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 transesophageal echocardiographic guidance.”
Lastly, Zahr and Lentz point out that it remains unclear whether paravalvular regurgitation predicts mortality as a result of adverse effects of residual high shear stress, or because it is a marker of other clinical risk factors.
To TCTMD, Susen said there are arguments
for both. “But the growing body of evidence shows that regurgitation by itself
modifies the LV dysfunction after the TAVR, and that is going to contribute to
mortality,” she concluded.
- Van Belle E, Rauch A, Vincent F, et al. Von Willebrand factor multimers during transcatheter aortic-valve replacement. N Engl J Med. 2016;375:335-344.
- Zahr FE, Lentz SR. Von Willebrand factor—a rapid sensor of paravalvular regurgitation during TAVR? N Engl J Med. 2016;375:382-383.
- Aortic Regurgitation Confirmed as Powerful Mortality Predictor after TAVR
- Preexisting Thrombocytopenia Worsens Complications After TAVR
- Thrombocytopenia Serves as Marker of Short- and Long-term Mortality after TAVR
- Susen reports no relevant conflicts of interest.
- Lentz is an investigator in NIH-funded programs designed to improve the diagnosis of von Willebrand disease, including the development and validation of new assays for von Willebrand factor.
- Zahr reports serving as a site sub-investigator for the PARTNER 2 trial.