Structural Valve Degeneration: VIVID Group Proposes New, Graduated Definition

A standardized definition to capture structural degeneration of surgical and transcatheter bioprosthetic aortic valves, as well as recommendations for the timing of clinical and imaging assessments, has been proposed by the Valve-in-Valve International Data (VIVID) group.

The definition and guidance are meant to provide clarity, particularly with regard to long-term surveillance of bioprosthetic aortic valves, according to Danny Dvir, MD (University of Washington, Seattle), lead author of the new report published January 22, 2018, in Circulation.

“Historically, structural valve degeneration of bioprosthetic valves has been regarded as the need to perform a redo intervention to replace the failed valve,” said Dvir. “But we know that this may severely underestimate the phenomenon of bioprosthetic degeneration, since many of these patients will not have repeat surgery, when they have structural valve degeneration, either don’t go to surgery or they go for surgery for other reasons. It’s not a very good barometer. Also, structural valve degeneration should not be defined as a binary parameter—it’s not yes or no. It’s a continuous phenomenon.’’

Matthew Brennan, MD (Duke Clinical Research Institute, Durham, NC), who was not involved in drafting the white paper, noted that the Valve Academic Research Consortium (VARC)-2 published a document in 2012 defining and standardizing TAVR clinical endpoints for future clinical trials that included a definition of structural valve deterioration. It was, however, based primarily on valve hemodynamics.

“As the technology has matured, we’re really starting to now focus on long-term outcomes,” said Brennan, referring to the need for nuanced, standardized definitions. “We’re more comfortable at this point that enough advancements have been made with the technology and we’re moving beyond early outcomes. But that then shifts the focus to long-term follow-up, and when you do that, you really need robust definitions for that long-term follow-up.”

The new standardized definition will provide guidance for future studies and clinical trials, particularly as researchers try to assess the degeneration rates of surgical and transcatheter bioprosthetic valves, according to the VIVID group.  

New Definition Reflects Time Course of Degeneration

The VIVID document defines structural valve degeneration as “an acquired intrinsic bioprosthetic valve abnormality defined as deterioration of the leaflets or supporting structures resulting in thickening, calcification, tearing, or disruption of the prosthetic valve materials with eventual associated valve hemodynamic dysfunction, manifested as stenosis or regurgitation.”

According to Dvir, the definition reflects the gradual degeneration of bioprosthetic valves over three distinct stages and subcategories, with stage 0 pointing to no significant hemodynamic change in the bioprosthetic valve when compared with the immediate postimplantation assessment. The other stages are determined as follows:    

• Stage 1: morphological leaflet abnormality (fluttering, thickening, and limited, delayed, or assymetrical leaflet opening or closure on echocardiography or other imaging) without any significant hemodynamic changes
• Stage 2S: moderate stenosis (increase in transvalvular mean gradient ≥ 10 mm Hg from baseline with a concomitant decrease in valve area not the result of thrombotic leaflet thickening)
• Stage 2R: moderate regurgitation
• Stage 2RS: moderate stenosis and moderate regurgitation
• Stage 3: severe stenosis and/or severe regurgitation

The VIVID experts recommend all patients undergo complete diagnostic transthoracic echocardiography (TTE) after the implantation of a surgical or transcatheter bioprosthetic aortic valve, since the results can provide baseline information for future studies. This would include imaging the valve prosthesis components; measuring antegrade velocity, mean gradient, and aortic valve effective orifice area; and evaluating any transvalvular or paravalvular prosthetic regurgitation. Additionally, the VIVID group recommends follow-up echocardiography at 30 days to identify early hemodynamic changes, such as acute increase in gradients, that may suggest a need to evaluate for leaflet thickening.

“There are many abnormalities that take a bit of time to be identified,” said Dvir. “Thirty days is a good time to understand whether the procedure was indeed effective, or whether more meticulous follow-up is needed.”

In general, said Dvir, the vast majority of patients who receive a bioprosthetic valve should undergo echocardiography annually so that signs of degeneration are not missed. For devices with proven long-term efficacy, a group that includes a select few surgical bioprosthetic valves, echocardiographic surveillance could be limited to the first year with a second follow-up at the 5-year-mark.

Brennan said that biologic valves used in surgery fail at 10 or 15 years, often later, but the evidence base for TAVR is not there.

“The initial experience with TAVR is that we were putting them into very sick patients who were not living very long,” he said. “As we move into the intermediate-risk patients, we have the potential to study these patients a lot longer. Now that we have that opportunity, the question is: what’s going to happen with these valves? There have been some reports about long-term performance that have been concerning, but most reports suggest they’re holding up very well.”  

The VIVID group notes that computed tomography, which allows physicians to better see the valve anatomy, is particularly helpful for detecting valve thrombosis and pannus formation. They also point out that changes associated with thrombosis can occur without hemodynamic changes on transthoracic echocardiography. While CT is not yet to be systematically performed in routine follow-up of TAVR or SAVR patients, Dvir and colleagues recommend its use if valve thrombosis and pannus formation are suspected.

Managing Patients With Prosthetic Valve Degeneration

In terms of how to manage patients in the various stages of degeneration, Dvir cautioned that the recommendations in the VIVID document are preliminary. “We have a lot to learn,” he said.

For those with normal prostheses (stage 0), annual clinical and echocardiographic follow-up is recommended. For those with leaflet abnormalities (stage 1), echocardiography should be repeated every 3 to 6 months (and then yearly if the patient is stable) and anticoagulation is recommended if leaflet thickening is suspected.

For those with stage 2 structural valve degeneration, including those with moderate stenosis and/or regurgitation, echocardiography should be repeated every 3 to 6 months after the diagnosis and then every 6 to 12 months if the patient is stable. Among those in stage 2RS, an intervention can be considered if the patient has symptoms.

Finally, for patients with stage 3 structural valve degeneration, the experts say reintervention is the recommended treatment when the patient is symptomatic. If asymptomatic with preserved left ventricular ejection fraction, clinical evaluation every 3 to 6 months and echocardiography every 6 months are advised.  

To TCTMD, Brennan said the new document will be particularly helpful in the research setting, but that there are also a few “clinical pearls” to help guide physicians seeing patients with different stages of valve degeneration. That said, most patients found to have moderate stenosis or regurgitation are already being followed a little more closely, as recommended in the document.

In September 2017, a similar consensus statement was published in the European Journal of Cardiothoracic Surgery by Davide Capodanno, MD (University of Catania, Italy). The European document, though, focuses not only on bioprosthetic valve degeneration but also on nonstructural deterioration (prosthesis malposition, patient-prosthesis mismatch, late embolization, among others), thrombosis, and endocarditis. Like the VIVID white paper’s authors, Capodanno and colleagues also recommend annual echocardiography for patients who received a bioprosthetic valve.