Native Aortic Valve Disease Progression and Bioprosthetic Valve Degeneration in Patients With Transcatheter Aortic Valve Implantation

Jacek Kwiecinski, Evangelos Tzolos, Timothy R G Cartlidge, Alexander Fletcher, Mhairi K Doris, Rong Bing, Jason M Tarkin, Michael A Seidman, Gaurav S Gulsin, Nicholas L Cruden, Anna K Barton, Neal G Uren, Michelle C Williams, Edwin J R van Beek, Jonathon Leipsic, Damini Dey, Raj R Makkar, Piotr J Slomka, James H F Rudd, David E Newby, Stephanie L Sellers, Daniel S Berman, Marc R Dweck, Jacek Kwiecinski, Evangelos Tzolos, Timothy R G Cartlidge, Alexander Fletcher, Mhairi K Doris, Rong Bing, Jason M Tarkin, Michael A Seidman, Gaurav S Gulsin, Nicholas L Cruden, Anna K Barton, Neal G Uren, Michelle C Williams, Edwin J R van Beek, Jonathon Leipsic, Damini Dey, Raj R Makkar, Piotr J Slomka, James H F Rudd, David E Newby, Stephanie L Sellers, Daniel S Berman, Marc R Dweck

Abstract

Background: Major uncertainties remain regarding disease activity within the retained native aortic valve, and regarding bioprosthetic valve durability, after transcatheter aortic valve implantation (TAVI). We aimed to assess native aortic valve disease activity and bioprosthetic valve durability in patients with TAVI in comparison with subjects with bioprosthetic surgical aortic valve replacement (SAVR).

Methods: In a multicenter cross-sectional observational cohort study, patients with TAVI or bioprosthetic SAVR underwent baseline echocardiography, computed tomography angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography. Participants (n=47) were imaged once with 18F-NaF positron emission tomography/computed tomography either at 1 month (n=9, 19%), 2 years (n=22, 47%), or 5 years (16, 34%) after valve implantation. Patients subsequently underwent serial echocardiography to assess for changes in valve hemodynamic performance (change in peak aortic velocity) and evidence of structural valve dysfunction. Comparisons were made with matched patients with bioprosthetic SAVR (n=51) who had undergone the same imaging protocol.

Results: In patients with TAVI, native aortic valves demonstrated 18F-NaF uptake around the outside of the bioprostheses that showed a modest correlation with the time from TAVI (r=0.36, P=0.023). 18F-NaF uptake in the bioprosthetic leaflets was comparable between the SAVR and TAVI groups (target-to-background ratio, 1.3 [1.2-1.7] versus 1.3 [1.2-1.5], respectively; P=0.27). The frequencies of imaging evidence of bioprosthetic valve degeneration at baseline were similar on echocardiography (6% versus 8%, respectively; P=0.78), computed tomography (15% versus 14%, respectively; P=0.87), and positron emission tomography (15% versus 29%, respectively; P=0.09). Baseline 18F-NaF uptake was associated with a subsequent change in peak aortic velocity for both TAVI (r=0.7, P<0.001) and SAVR (r=0.7, P<0.001). On multivariable analysis, 18F-NaF uptake was the only predictor of peak velocity progression (P<0.001).

Conclusions: In patients with TAVI, native aortic valves demonstrate evidence of ongoing active disease. Across imaging modalities, TAVI degeneration is of similar magnitude to bioprosthetic SAVR, suggesting comparable midterm durability. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02304276.

Keywords: 18F-sodium fluoride; aortic valve; positron emission tomography computed tomography; transcatheter aortic valve implantation.

Figures

Figure 1.
Figure 1.
CONSORT flow diagram of study recruitment, allocation (assessments), follow-up, and analysis. CT indicates computed tomography; and 18F-NaF PET, 18F-sodium fluoride positron emission tomography.
Figure 2.
Figure 2.
Baseline assessment with 18F-sodium fluoride activity in native aortic valve tissue after transcatheter aortic valve replacement.A, Hybrid 18F-sodium fluoride (18F-NaF) positron emission tomography and computed tomography en face and long-axis images of native aortic valve tissue uptake. We observed intense tracer activity originating from the native valve tissue around the perimeter of the bioprosthesis in all patients with transcatheter aortic valve implantation (TAVI). B, Native aortic valve 18F-NaF uptake in patients with TAVI was higher with longer duration because bioprosthesis implantation suggesting increased calcification activity after intervention. C, Representative macroscopic images of explanted TAVI valves (green arrow) surrounded by native aortic valve (red arrow) jailed between the bioprostheses and the aortic root (blue arrow): ventricular aspect (Left), aortic aspect (Middle), and view of the root with native valve tissue cut and opened out along its perimeter (Right). D, Histology (Movat pentachrome staining) and immunohistochemistry of native aortic valves showing morphology, high expression of Runx2 and osteopontin in the native aortic valves explanted 1, 32, and 53 months after TAVI. TBR indicates target-to-background ratio.
Figure 3.
Figure 3.
18F-Sodium fluoride identifies early TAVI bioprosthetic valve degeneration.A, Top, A 76-year-old woman with hemodynamic valve deterioration on echocardiography imaged 5 years after transcatheter aortic valve implantation (TAVI). Computed tomography angiography revealed spotty calcification on the bioprosthetic leaflets. On 18F-sodium fluoride (18F-NaF) positron emission tomography, we detected very high uptake in the leaflets (target-to-background [TBR]=5.9). The patient developed bioprosthesis failure 18 months after baseline positron emission tomography and underwent a successful TAVI-in-TAVI. Middle, An 88-year-old man with hemodynamic valve deterioration on echocardiography imaged 5 years after TAVI. Computed tomography angiography revealed hypoattenuated leaflet thickening. On 18F-NaF positron emission tomography we detected very high uptake in the leaflets (TBR=3.8). B, There was a stepwise increase in TAVI 18F-NaF uptake according to the presence and severity of valve dysfunction. 18F-NaF uptake was highest in patients with hemodynamic dysfunction, and more pronounced in those with structural valve deterioration (SVD) than normal TAVI valves. C, Histological and autoradiography validation of 18F-NaF avidity in an Edwards Conformitè Europëenne (CE) TAVI valve explanted after 86 months: Movat pentachrome and hematoxylin and eosin (H&E) staining demonstrate that leaflet calcification corresponds closely with 18F-NaF binding on autoradiography. THV indicates transcatheter heart valve.
Figure 4.
Figure 4.
Baseline 18F-sodium fluoride uptake predicts subsequent deterioration in TAVI function.A, Case example of an 84-year-old patient imaged 5 years after transcatheter aortic valve implantation (TAVI). We detected TAVI 18F-sodium fluoride (18F-NaF) leaflet uptake in the absence of abnormalities on echocardiography (mean pressure gradient 11 mm Hg) and computed tomography (CT). At follow-up, the patient developed moderate bioprosthesis stenosis with a mean pressure gradient of 23 mm Hg. B, A strong correlation was observed between baseline 18F-NaF uptake in the TAVI valves (TBR) and subsequent progression in bioprosthetic valve peak velocity (r=0.7; P<0.001). C, Forest plot of unstandardized coefficients (95% CIs) from a multivariable linear regression analysis predicting change in TAVI valve function (annualized change in peak velocity) during follow-up. When examining all relevant baseline characteristics, 18F-NaF uptake was the only independent predictor of hemodynamic TAVI deterioration. PET indicates positron emission tomography; and TBR, target-to-background ratio.
Figure 5.
Figure 5.
Comparison of imaging findings and valve deterioration in TAVI vs bioprosthetic SAVR. We compared echocardiographic, computed tomography (CT) and 18F-sodium fluoride (18F-NaF) findings in 47 patients with transcatheter aortic valve implantation (TAVI) with 51 patients with surgical aortic valve replacement (SAVR) who underwent the same research imaging protocol. We observed 18F-NaF uptake on the peripheral of all TAVI valves and none of the SAVR valves. Although patients with TAVI showed lower peak velocity (2.4 [2.0–2.7] vs 2.7 [2.4–3.0] m/s; P=0.03) and larger effective orifice area (1.5 [1.3–1.8] vs 1.1 [1.0–1.5] cm2; P=0.02) than patients with SAVR, we detected baseline echocardiographic (6% vs 8%; P=0.78) and CT abnormalities (15% vs 14%; P=0.87) suggestive of bioprosthetic degeneration in a similar proportion of patients with either TAVI or SAVR. The overall prevalence of patients with increased leaflet 18F-NaF uptake was nearly double in patients with SAVR compared with those with TAVI (29% and 15%; P=0.09). In both patients with SAVR or TAVI, baseline 18F-NaF leaflet uptake was predictive of the change in the peak transvalvular velocity on echocardiography. PET indicates positron emission tomography; and TBR, target-to-background ratio.

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