PERSPECTIVES OPINION
Transcatheter aortic valve implantation in bicuspid anatomy Zhen-Gang Zhao, Hasan Jilaihawi, Yuan Feng and Mao Chen Abstract | Transcatheter aortic valve implantation (TAVI) is an established therapeutic option for high-risk patients with tricuspid aortic valve stenosis. Historically, the presence of a bicuspid aortic valve (BAV) has been regarded as a contraindication to TAVI, on the basis of putative concerns about the associated risks of elliptical deployment, accelerated leaflet degeneration, periprosthetic leaks, and aortic complications. Fortunately, with technological refinements and mounting experience, reasonable success has been achieved with TAVI in selected patients with a BAV. The rate of procedural success is high, and survival is similar to that in patients with a tricuspid aortic valve who undergo TAVI. Nevertheless, moderate or severe aortic regurgitation and aortic dissection seem to occur more frequently in patients with a BAV rather than a tricuspid aortic valve. Specifically-designed prospective studies should address these concerns and help to define anatomical selection criteria before TAVI can be recommended for patients with a BAV. Zhao, Z.‑G. et al. Nat. Rev. Cardiol. advance online publication 14 October 2014; doi:10.1038/nrcardio.2014.161
Introduction
Transcatheter aortic valve implantation (TAVI) is an emerging treatment modality for aortic stenosis that has been shown to be noninferior to conventional aortic valve replacement (AVR) in patients at high surgical risk.1–3 Interestingly, the landmark, first-in-human TAVI by Cribier and colleagues in 2002 was actually performed in a patient with a bicuspid aortic valve (BAV).4 Ironically, having a BAV has long been considered a contraindication to undergoing the procedure, and individuals with this anatomy have generally been excluded from TAVI trials.2,5 Major concerns focus on the unfavourable anatomy observed with this common congenital anomaly (affecting 0.5– 2.0% of the general population6–9), including annular eccentricity, asymmetrical valve calcification, unequally-sized leaflets, and concomitant aortopathy.10–13 These factors might increase the risk of elliptical deployment, impair bioprosthesis durability, Competing interests H.J. declares that he is a consultant for Edwards Lifesciences, St. Jude Medical, and Venus MedTech. The other authors declare no competing interests.
and cause residual aortic regurgitation, annulus rupture, coronary obstruction, and aortic complications.10–13 The number of patients who are unsuitable for AVR and who have also been exclu ded from undergoing TAVI simply owing to a BAV anatomy is unknown, but the available data suggest that the number might be substantial (Figure 1).12–29 Overall, >20% of octogenarians undergoing isolated AVR for aortic stenosis have a BAV.30,31 With the evolution of devices, refinement of techniques, and accumulation of experience, off-label uses of TAVI have increased dramatically over time. The application of TAVI in BAV stenosis is undoubtedly one of the most controversial and promising frontiers in the field of cardiovascular intervention.32 Now that TAVI is approaching its technical maturity and being performed in younger patients, among whom BAV is even more prevalent than in older patients,30 a return to the controversial issue of TAVI in BAV stenosis is warranted. In contrast to the tremendous growth in the use of TAVI over the past decade, with an estimated 150,000 patients being treated worldwide, experience of this technique in patients with BAV stenosis is scarce.12–29
NATURE REVIEWS | CARDIOLOGY
None of the reported BAV cohorts has an adequate sample size from which to draw firm conclusions. Therefore, in this Perspectives article, we summarize the available data in the published literature, and compare the results of TAVI in patients with a bicuspid or tricuspid anatomy.
Current experience Baseline characteristics A total of 17 studies of TAVI including 163 patients with a BAV were identified (Table 1).12–28 Main baseline characteristics were similar between individuals with a BAV and those with a tricuspid aortic valve, except that the former were on average 3.5 years younger and tended to have a slightly lower logistic EuroSCORE (19.9% ± 10.8% versus 21.4% ± 14.3%; Table 2). Measurements of aortic root dimensions were not systematically reported (Table 2). The diameter and extent of eccentricity of the annulus were not significantly different between the two groups, whereas the ascending aorta of patients with a BAV was more dilated (38.8 ± 5.0 mm versus 35.3 ± 4.2 mm; P 24
81.8§
Chen et al. (2013)15
18
100.0
100.0
0–1: 55.6 2: 38.9 3: 5.6
94.1
15
88.9
Bauer et al. (2013)16
38
68.4
84.25
0–2: 73.7 3–4: 26.3
89.5
12
87.0
Costopoulos et al. (2014)17
21
61.9
95.2
0–1: 76.2 2: 23.8
85.7
15
68.4
Kochman et al. (2014)18
28
85.7
82.1
0–1: 67.9 2–3: 32.1
96.4
11
82.1
Chiam et al. (2009)19
1
0
100.0
0–1: 100.0
100.0
6
100.0
Delgado et al. (2009)20
1
0
100.0
0–2: 100.0
100.0
NA
NA
Ferrari et al. (2009)
1
0
0
0–1: 100.0
NA
NA
NA
Raja et al. (2011)22
1
0
100.0
2: 100.0
100.0
10
100.0
Jilaihawi et al. (2010)
1
100.0
100.0
2: 100.0
100.0
24
100.0
Maeda et al. (2012)24
1
0
100.0
0–1: 100.0
NA
NA
NA
Zegdi et al. (2012)25
1
0
100.0
0–1: 100.0
100.0
NA
NA
26
Rodríguez et al. (2012)
1
0
0
0–1: 100.0
100.0
12
100.0
Maluenda et al. (2012)27
1
0
100.0
2: 100.0
100.0
NA
NA
Segev et al. (2013)28
1 1
0 0
0 100.0
0–2: 100.0 0–2: 100.0
100.0 100.0
NA NA
NA NA
Case series
Case reports
21
23
*CoreValve®(Medtronic CV Luxembourg S.a.r.l., Luxembourg). ‡Aortic regurgitation grade: 0 = none, 1 = trivial, 2 = mild, 3 = moderate, and 4 = severe. §Follow-up data available in only 11 patients. Abbreviations: n, number of patients; NA, not available; TAVI, transcatheter aortic valve implantation.
literature. However, considering the low use of balloon-expandable valves—a device th eoretically more likely than a selfexpandablevalve to cause rupture in the presence of bulky asymmetric calcification—the results should be interpreted with caution. Large annulus Although the mean aortic annulus diameter in patients undergoing TAVI for BAV sten osis does not differ from that in patients with a tricuspid aortic valve, patients with a BAV are twice as likely to be implanted with the largest valve, as mentioned above. The reasons for this are unclear, but might be associated with the larger overall root anatomy (sinuses of Valsalva, sinotubular junction), generally observed with a BAV. Nevertheless, valve sizing for patients with a BAV remains problematic. Usually, the free edge of the BAV leaflets is only about two-thirds of the annulus circumference.25
Therefore, adoption of a sizing strategy based on annulus diameter with mild oversizing could lead to dehiscence of the native leaflets and subsequent prosthesis migration owing to the lack of anchoring support.25,38 However, valve undersizing has long been regarded as the main cause of prosthesis migration and paravalvular leak.39,40 A balloon-sizing strategy might be a more accurate and effective strategy to minimize the risk of both of these complications.41
Persistent concerns Residual aortic regurgitation Moderate or severe aortic regurgitation after TAVI is considerably more prevalent in patients with BAV stenosis than in those with tricuspid anatomy. A growing body of evidence suggests that even mild aortic regurgitation carries an increased risk of death.1,42–44 Unexpectedly, patients with a BAV in the German TAVI Registry
NATURE REVIEWS | CARDIOLOGY
had satisfactory 30‑day and 1‑year survival (similar to that in patients with a tricuspid aortic valve), despite a 10% higher rate of moderate or severe aortic regurgitation.16 Notably, the younger age of patients with a BAV undergoing TAVI is an important confounder. Indeed, in the BAV group, patients with moderate or severe residual aortic regurgitation had much higher 1‑year mortality than those with less severe aortic regurgitation (22% versus 7%), although the number of patients was small.16 Whether the aortic regurgitation was paravalvular or central was rarely specified, but the latter is generally rare. The occurrence of paravalvular aortic regurgitation has a multifactorial basis.44 An unfavourable distribution of leaflet calcification, which can distort the valve stent or prevent it from complete apposition to the device landing zone, has been suggested to be particularly important, but data on this topic from ADVANCE ONLINE PUBLICATION | 3
© 2014 Macmillan Publishers Limited. All rights reserved
PERSPECTIVES Table 2 | TAVI in bicuspid versus tricuspid aortic valves Parameter
Patients with a BAV
Matched patients with a TAV
P value
Number of studies
Number of patients
Estimates
Number of studies
Number of patients
Estimates
Age (years)
7
152
78.3 ± 8.1
7
3,318
81.8 ± 6.8
Transcatheter aortic valve implantation in bicuspid anatomy Zhen-Gang Zhao, Hasan Jilaihawi, Yuan Feng and Mao Chen Abstract | Transcatheter aortic valve implantation (TAVI) is an established therapeutic option for high-risk patients with tricuspid aortic valve stenosis. Historically, the presence of a bicuspid aortic valve (BAV) has been regarded as a contraindication to TAVI, on the basis of putative concerns about the associated risks of elliptical deployment, accelerated leaflet degeneration, periprosthetic leaks, and aortic complications. Fortunately, with technological refinements and mounting experience, reasonable success has been achieved with TAVI in selected patients with a BAV. The rate of procedural success is high, and survival is similar to that in patients with a tricuspid aortic valve who undergo TAVI. Nevertheless, moderate or severe aortic regurgitation and aortic dissection seem to occur more frequently in patients with a BAV rather than a tricuspid aortic valve. Specifically-designed prospective studies should address these concerns and help to define anatomical selection criteria before TAVI can be recommended for patients with a BAV. Zhao, Z.‑G. et al. Nat. Rev. Cardiol. advance online publication 14 October 2014; doi:10.1038/nrcardio.2014.161
Introduction
Transcatheter aortic valve implantation (TAVI) is an emerging treatment modality for aortic stenosis that has been shown to be noninferior to conventional aortic valve replacement (AVR) in patients at high surgical risk.1–3 Interestingly, the landmark, first-in-human TAVI by Cribier and colleagues in 2002 was actually performed in a patient with a bicuspid aortic valve (BAV).4 Ironically, having a BAV has long been considered a contraindication to undergoing the procedure, and individuals with this anatomy have generally been excluded from TAVI trials.2,5 Major concerns focus on the unfavourable anatomy observed with this common congenital anomaly (affecting 0.5– 2.0% of the general population6–9), including annular eccentricity, asymmetrical valve calcification, unequally-sized leaflets, and concomitant aortopathy.10–13 These factors might increase the risk of elliptical deployment, impair bioprosthesis durability, Competing interests H.J. declares that he is a consultant for Edwards Lifesciences, St. Jude Medical, and Venus MedTech. The other authors declare no competing interests.
and cause residual aortic regurgitation, annulus rupture, coronary obstruction, and aortic complications.10–13 The number of patients who are unsuitable for AVR and who have also been exclu ded from undergoing TAVI simply owing to a BAV anatomy is unknown, but the available data suggest that the number might be substantial (Figure 1).12–29 Overall, >20% of octogenarians undergoing isolated AVR for aortic stenosis have a BAV.30,31 With the evolution of devices, refinement of techniques, and accumulation of experience, off-label uses of TAVI have increased dramatically over time. The application of TAVI in BAV stenosis is undoubtedly one of the most controversial and promising frontiers in the field of cardiovascular intervention.32 Now that TAVI is approaching its technical maturity and being performed in younger patients, among whom BAV is even more prevalent than in older patients,30 a return to the controversial issue of TAVI in BAV stenosis is warranted. In contrast to the tremendous growth in the use of TAVI over the past decade, with an estimated 150,000 patients being treated worldwide, experience of this technique in patients with BAV stenosis is scarce.12–29
NATURE REVIEWS | CARDIOLOGY
None of the reported BAV cohorts has an adequate sample size from which to draw firm conclusions. Therefore, in this Perspectives article, we summarize the available data in the published literature, and compare the results of TAVI in patients with a bicuspid or tricuspid anatomy.
Current experience Baseline characteristics A total of 17 studies of TAVI including 163 patients with a BAV were identified (Table 1).12–28 Main baseline characteristics were similar between individuals with a BAV and those with a tricuspid aortic valve, except that the former were on average 3.5 years younger and tended to have a slightly lower logistic EuroSCORE (19.9% ± 10.8% versus 21.4% ± 14.3%; Table 2). Measurements of aortic root dimensions were not systematically reported (Table 2). The diameter and extent of eccentricity of the annulus were not significantly different between the two groups, whereas the ascending aorta of patients with a BAV was more dilated (38.8 ± 5.0 mm versus 35.3 ± 4.2 mm; P 24
81.8§
Chen et al. (2013)15
18
100.0
100.0
0–1: 55.6 2: 38.9 3: 5.6
94.1
15
88.9
Bauer et al. (2013)16
38
68.4
84.25
0–2: 73.7 3–4: 26.3
89.5
12
87.0
Costopoulos et al. (2014)17
21
61.9
95.2
0–1: 76.2 2: 23.8
85.7
15
68.4
Kochman et al. (2014)18
28
85.7
82.1
0–1: 67.9 2–3: 32.1
96.4
11
82.1
Chiam et al. (2009)19
1
0
100.0
0–1: 100.0
100.0
6
100.0
Delgado et al. (2009)20
1
0
100.0
0–2: 100.0
100.0
NA
NA
Ferrari et al. (2009)
1
0
0
0–1: 100.0
NA
NA
NA
Raja et al. (2011)22
1
0
100.0
2: 100.0
100.0
10
100.0
Jilaihawi et al. (2010)
1
100.0
100.0
2: 100.0
100.0
24
100.0
Maeda et al. (2012)24
1
0
100.0
0–1: 100.0
NA
NA
NA
Zegdi et al. (2012)25
1
0
100.0
0–1: 100.0
100.0
NA
NA
26
Rodríguez et al. (2012)
1
0
0
0–1: 100.0
100.0
12
100.0
Maluenda et al. (2012)27
1
0
100.0
2: 100.0
100.0
NA
NA
Segev et al. (2013)28
1 1
0 0
0 100.0
0–2: 100.0 0–2: 100.0
100.0 100.0
NA NA
NA NA
Case series
Case reports
21
23
*CoreValve®(Medtronic CV Luxembourg S.a.r.l., Luxembourg). ‡Aortic regurgitation grade: 0 = none, 1 = trivial, 2 = mild, 3 = moderate, and 4 = severe. §Follow-up data available in only 11 patients. Abbreviations: n, number of patients; NA, not available; TAVI, transcatheter aortic valve implantation.
literature. However, considering the low use of balloon-expandable valves—a device th eoretically more likely than a selfexpandablevalve to cause rupture in the presence of bulky asymmetric calcification—the results should be interpreted with caution. Large annulus Although the mean aortic annulus diameter in patients undergoing TAVI for BAV sten osis does not differ from that in patients with a tricuspid aortic valve, patients with a BAV are twice as likely to be implanted with the largest valve, as mentioned above. The reasons for this are unclear, but might be associated with the larger overall root anatomy (sinuses of Valsalva, sinotubular junction), generally observed with a BAV. Nevertheless, valve sizing for patients with a BAV remains problematic. Usually, the free edge of the BAV leaflets is only about two-thirds of the annulus circumference.25
Therefore, adoption of a sizing strategy based on annulus diameter with mild oversizing could lead to dehiscence of the native leaflets and subsequent prosthesis migration owing to the lack of anchoring support.25,38 However, valve undersizing has long been regarded as the main cause of prosthesis migration and paravalvular leak.39,40 A balloon-sizing strategy might be a more accurate and effective strategy to minimize the risk of both of these complications.41
Persistent concerns Residual aortic regurgitation Moderate or severe aortic regurgitation after TAVI is considerably more prevalent in patients with BAV stenosis than in those with tricuspid anatomy. A growing body of evidence suggests that even mild aortic regurgitation carries an increased risk of death.1,42–44 Unexpectedly, patients with a BAV in the German TAVI Registry
NATURE REVIEWS | CARDIOLOGY
had satisfactory 30‑day and 1‑year survival (similar to that in patients with a tricuspid aortic valve), despite a 10% higher rate of moderate or severe aortic regurgitation.16 Notably, the younger age of patients with a BAV undergoing TAVI is an important confounder. Indeed, in the BAV group, patients with moderate or severe residual aortic regurgitation had much higher 1‑year mortality than those with less severe aortic regurgitation (22% versus 7%), although the number of patients was small.16 Whether the aortic regurgitation was paravalvular or central was rarely specified, but the latter is generally rare. The occurrence of paravalvular aortic regurgitation has a multifactorial basis.44 An unfavourable distribution of leaflet calcification, which can distort the valve stent or prevent it from complete apposition to the device landing zone, has been suggested to be particularly important, but data on this topic from ADVANCE ONLINE PUBLICATION | 3
© 2014 Macmillan Publishers Limited. All rights reserved
PERSPECTIVES Table 2 | TAVI in bicuspid versus tricuspid aortic valves Parameter
Patients with a BAV
Matched patients with a TAV
P value
Number of studies
Number of patients
Estimates
Number of studies
Number of patients
Estimates
Age (years)
7
152
78.3 ± 8.1
7
3,318
81.8 ± 6.8
