Transcatheter aortic valve replacement (TAVR) has proven to be a safe, effective, and less invasive approach to aortic valve replacement in patients with aortic stenosis. In patients who underwent prior aortic valve replacement, transcatheter and surgical bioprosthetic valve dysfunction may occur as a result of structural deterioration or nonstructural causes such as prosthesis–patient mismatch (PPM) and paravalvular regurgitation. Valve-in-Valve (ViV) TAVR is a procedure that is being increasingly utilized for the replacement of failed transcatheter or surgical bioprosthetic aortic valves.
1. Bioprosthetic Valve Dysfunction
Based on the 2020 ACC/AHA guidelines, ViV TAVR carries a class IIa recommendation for high-risk surgical patients with symptomatic aortic valve stenosis or regurgitation as a result of transcatheter or surgical bioprosthetic valve dysfunction
[1]. Prosthetic valve dysfunction is most often caused by either the structural degeneration of the valve leaflets or non-structural causes
[1][2][3]. Structural valve deterioration is often the result of wear and tear, leaflet disruption, flail leaflet, leaflet fibrosis and/or calcification, or strut deformation that results in permanent damage to the prosthetic valve
[2][3][4]. Non-structural valve dysfunction includes any abnormality that is not intrinsic to the function of the valve itself
[1][2]. This is often due to paravalvular regurgitation or prosthesis–patient mismatch (PPM), but it may also result from leaflet entrapment, aortic root dilatation, and valve migration/embolization
[1][2][3]. Bioprosthetic valve dysfunction may also occur as a result of thrombosis or endocarditis
[2]. The most recent Valve Academic Research Consortium (VARC-3) definitions characterize bioprosthetic valve dysfunction by the extent of hemodynamic changes, and the dysfunction is considered as bioprosthetic failure once the patient becomes symptomatic or experiences irreversible hemodynamic valve deterioration (HVD)
[2]. Stage 1 HVD is characterized by the presence of structural or non-structural valve deterioration without hemodynamic changes
[2]. Stage 2 HVD (moderate HVD) is determined by an increase in mean transvalvular gradient ≥ 10 mmHg resulting in a mean gradient of ≥ 20 mmHg, in addition to a decrease in estimated orifice area (EOA) by ≥ 0.3 cm
2 (or by ≥ 25%) or a decrease in doppler velocity index by ≥ 0.1 (or ≥ 20%) when compared to an echocardiogram performed 1–3 months post-procedure
[2]. Stage 3 HVD (severe HVD) is defined by an increase in mean transvalvular gradient ≥ 20 mmHg resulting in a mean gradient of ≥ 30 mmHg, in addition to a decrease in EOA by ≥ 0.6 cm
2 (or by ≥ 50%) or a decrease in doppler velocity index by ≥ 0.2 (or ≥ 40%) when compared to an echocardiogram performed 1–3 months post-procedure
[2]. Stage 2 and stage 3 HVD may also be characterized by new or worsening intra-prosthetic aortic regurgitation (AR), resulting in moderate and severe AR, respectively
[2]. Due to the variability in echocardiographic imaging and assessment, it is recommended that a definitive diagnosis of bioprosthetic valve dysfunction should be based on the results from two serial echocardiograms
[2].
2. Paravalvular Regurgitation
Paravalvular regurgitation affects 5–17% of all surgical prosthetic valves and occurs when blood leaks through the space between the native heart and the prosthetic valve
[5][6]. This may be a result of annular calcification, eccentricity of the annulus, undersizing of the device, or malpositioning of the valve during deployment
[4][7]. A recent meta-analysis of 30 RCTs and observational studies found that 7–40% of THVs resulted in paravalvular regurgitation and 10–25% of cases were considered to be either moderate or severe
[7]. For acute paravalvular leaks, repeated post-balloon dilation of an underexpanded valve or the use of a snare loop-assisted device to reposition the valve may minimize significant regurgitation
[4][7]. For non-acute paravalvular regurgitation, transcatheter vascular plugs may be utilized to close the paravalvular leak, but these procedures increase the risk of THV embolization and stroke
[4][7]. In patients with a surgical bioprosthetic valve that can be fractured, ViV TAVR can be considered, though most patients with low surgical risk will undergo SAVR
[4]. In order to reduce the likelihood of paravalvular regurgitation, newer generations of THVs are designed to be repositioned and have a better seal within the native valve annulus
[7].
3. Prosthesis–Patient Mismatch
PPM occurs when the implanted THV is too small in relation to the patient’s body size, resulting in a smaller orifice area of the prosthetic valve, increased aortic valve gradients, and diminished cardiac output
[5][8][9]. Studies have demonstrated that PPM leads to increased re-admission rates (often for heart failure or redo valve replacement) and significantly reduces long-term survival
[8][10]. The severity of prothesis–patient mismatch is determined using the indexed effective orifice area (iEOA). This is calculated by dividing the effective orifice area by the patient’s body surface area
[8]. Severe PPM is defined as an iEOA of ≤ 0.65 in patients with a BMI < 30 and ≤ 0.55 in pts with a BMI ≥ 30
[2][8]. Although there is a clear inverse relationship between iEOA and aortic mean gradients, this cut-off value may have minimal clinical significance
[8]. Rather than using iEOA values outlined in the VARC-3, some studies will define PPM as a mean aortic valve gradient of ≥ 20 mmHg calculated using echocardiography
[8][11]. This is consistent with the mean aortic gradients used in the VARC-3 definition of moderate or severe HVD
[2]. Rates of severe PPM have been shown to be higher in patients who undergo SAVR as compared to those who undergo TAVR
[12][13][14]. Severe PPM after SAVR has led to higher mortality rates and heart failure hospitalizations; however, the evidence related to outcomes of severe PPM after TAVR remains limited
[12][13][14]. Schofer et al., used VARC-2 definitions to determine moderate and severe PPM in a study of 1309 post-TAVR patients
[15]. In this study, moderate and severe PPM occurred at rates of 22.9% and 12.9%, respectively
[15]. Patients with an EF < 40% and severe PPM had significantly higher three-year mortality rates compared to those without PPM (45.1% vs. 68.0%,
p = 0.041)
[15]. In patients with an EF ≥ 40% and severe PPM, there was no significant difference in three-year mortality rate as compared to patients without PPM (29.5% vs. 34.6%,
p = 0.96)
[15].
Currently, self-expanding supra-annular valves are the preferred THV platform to reduce the risk of PPM in TAVR patients. Several studies have shown a lower incidence of moderate and severe PPM in self-expanding valves as compared to balloon-expanding valves
[16][17][18][19][20]. In a large study comparing THV designs, patients who underwent TAVR with Evolut (self-expanding supra-annular valve) and Portico (self-expanding intra-annular valve) valves had similar increases in mean pressure gradients (7 mmHg) at 30 days post-TAVR despite the difference in positioning
[19]. Both valves performed better when compared to the Sapien 3 balloon-expandable intra-annular valve (12 mmHg increase in mean pressure gradient at 30 days post-TAVR)
[19]. However, in patients with small and very small native annulus, rates of moderate PPM were significantly higher with the Portico intra-annular valves as compared to the Evolut supra-annular valves
[20]. In another study, intra-annular devices resulted in higher rates of moderate PPM (17.7% vs. 8.9%,
p < 0.05) and severe PPM (1.6% vs. 0%,
p < 0.05) compared to supra-annular valves, but these data are from older THV models and ultimately had no impact on 10-year survival
[17].