Initial Outcomes After Trans-Right Subclavian Transcatheter Aortic Valve Implantation

Abstract

Background

Trans-subclavian access transcatheter aortic valve implantation (TAVI), typically from the left side, is feasible. However, right subclavian artery access is technically challenging because of the anatomical orientation, resulting in malalignment of the transcatheter heart valve within the aortic annular plane.

Methods and Results

We aimed to evaluate procedural outcomes, device–annulus alignment, and clinical efficacy of right trans-subclavian (RtTS) TAVI. Of a consecutive 423 patients who underwent TAVI, 32 cases performed via right and left subclavian access were analyzed. Implanted device depth and angle were analyzed angiographically. The device–annulus angle was measured angiographically. Fifteen of 22 patients were treated with a balloon-expandable valve, and 7 patients received a self-expanding valve, via RtTS. Procedural success was achieved in all cases. Compared with femoral and left subclavian approaches, RtTS led to a significantly larger device–annulus angle (6.0° vs. 8.7°; P<0.05), with deep left coronary cusp implantation (2.4 vs. 4.4 mm; P=0.05). Post-procedural transcatheter heart valve function was comparable across the groups, and no patients had greater than moderate paravalvular leakage. However, the incidence of symptomatic stroke occurred in 2 patients in the RtTS group (9.1%; P=0.21).

Conclusions

RtTS TAVI is a feasible alternative access route, with comparable procedural and clinical outcomes to those of conventional approaches, albeit with a higher risk of stroke.

Central Figure.

Transcatheter aortic valve implantation (TAVI) has revolutionized the management of severe aortic stenosis, offering a less invasive alternative to surgical aortic valve replacement, particularly in elderly patients and those with a high surgical risk.^1,2 Transfemoral (TF) access remains the gold standard because of its ease of approach and favorable outcomes.³ However, peripheral arterial disease, severe calcifications, or tortuosity may preclude femoral access in approximately 10–15% of patients, necessitating alternative access strategies.^4,5 Among these alternatives, the trans-subclavian route has emerged as a preferred option because of its proximity to the aortic root and favorable outcomes compared with transapical or transaortic approaches.^6–8 The left subclavian artery is typically favored because of its anatomical alignment with the aortic annulus. Conversely, the right subclavian artery presents challenges related to the acute angle of entry into the aortic arch, which makes it difficult to maintain the transcatheter heart valve (THV) within the annular plane. Despite these anatomical limitations, right subclavian TAVI may be the only feasible option in certain clinical scenarios, such as patients with occluded left subclavian arteries, prior left internal mammary artery grafts, or anatomical anomalies. However, data on the procedural feasibility, anatomical considerations, and clinical outcomes of right subclavian TAVI remain limited.

This study aimed to evaluate the initial clinical experience of right trans-subclavian (RtTS) TAVI and evaluated the procedural outcomes, device–annulus alignment, and early clinical efficacy compared with left trans-subclavian (LtTS) TAVI.

Methods

Study Design and Population

This retrospective, observational study included 423 consecutive patients who underwent TAVI at Kindai University Hospital between January 2019 and January 2023. Among patients undergoing TAVI, those who underwent subclavian access were enrolled and divided into 2 groups: LtTS; and RtTS. The indications for subclavian access comprised iliofemoral artery disease (severe calcification, tortuosity, small vessel diameter) and anatomical contraindications to femoral access. The decision to proceed with right subclavian access was made after multidisciplinary heart team discussions. The RtTS was selected when the vascular characteristics of the LtTS were unsuitable.

Ethics Statement

The study was approved by the Ethics Committee of Kindai University Faculty of Medicine and was conducted according to the principles of the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all participants after an explanation of the study’s purpose and protocol. This study was approved by the Ethics Committee of Kindai University Hospital (R03-040), and written informed consent was obtained from all patients.

Procedural Technique and Tips for Implantation

THV deployment was performed using either a balloon-expandable valve (BEV; SAPIEN 3; Edwards Lifesciences, Irvine, CA, USA) or a self-expanding valve (SEV; Evolut by Medtronic Cardiovascular, Santa Rosa, CA, USA, or Navitor by Abbott Structural Heart, St Paul, MN, USA). Both right and left subclavian access were achieved via surgical cut-down. Devices entered the annulus plane at the point of system insertion and not perpendicular to the annulus plane but, rather, tilted to the left coronary cusp (LCC) side. As a result, device deployment began with the non-coronary cusp (NCC) in a shallow position and the LCC side in a deep position. Notably, BEVs tilt coaxially as the valve expands; SEVs also collapse along the axis with the NCC as the valve deploys. The tips of both valves tilt coaxially on the NCC axis; thus, the NCC position was used to adjust the height of the valve (Figure 1).

Figure 1.

Angle and tilt during right trans-subclavian (RtTS) access transcatheter aortic valve implantation. (A–C) Balloon-expandable valve. (D–F) Self-expanding valve. BEV, balloon-expandable valve; SEV, self-expanding valve.

Endpoints and Definitions

The primary endpoint was procedural success and device success at 30 days, defined in accordance with the Valve Academic Research Consortium 3 criteria.⁹ Secondary endpoints include device-annulus angle evaluated angiographically (Figure 2), and incidence of new permanent pacemaker implantation (PPI) and symptomatic stroke.

Figure 2.

Implanted device angle and depth on angiography. LCC, left coronary cusp; NCC, non-coronary cusp.

Statistical Analysis

Statistical analyses were performed using JMP v. 13.0 (SAS Institute, Cary, NC, USA). Continuous variables were expressed as mean±standard deviation and compared using the Student’s t-test or analysis of variance, as appropriate. Continuous variables that did not conform to normal distribution was expressed as median (interquartile range), and comparisons between groups were made using the Mann-Whitney U test. Categorical variables were analyzed using the Chi-square or Fisher’s exact test, and P<0.05 was considered statistically significant.

Results

Baseline Characteristics

Among 423 patients, the TF group comprised 391 (92.4%) patients, the LtTS group comprised 10 (2.3%) patients, and the RtTS group comprised 22 (5.2%) patients. The reasons for selecting right subclavian artery access for each patient are listed in Table 1. In 16 of 22 cases, left subclavian artery access was unsuitable due to stenosis of the left subclavian artery or plaque deposits extending to the aortic arch. In 3 cases, an aneurysm of the distal aortic arch involving the left subclavian artery caused selection of the right subclavian artery. In another 3 cases, the RtTS was chosen to avoid disturbance of the left arm arteriovenous shunt for hemodialysis.

Table 1.

Individual Reasons for Selection of RtTS Access and Implanted Device

No.	Age (years)	Sex	Reason for RtTS access	Aortic angle (°)	Device
1	86	M	Aortic arch near the left SCA plaque+	51.5	Evolut R; 29 mm
2	88	F	Left SCA; stenosis+	50.3	Evolut Pro+; 29 mm
3	83	F	Aortic aneurysm of distal arch involving the left SCA	45.4	Evolut Pro+; 26 mm
4	84	M	Arteriovenous shunt on the left arm for hemodialysis	42.0	SAPIEN 3; 23 mm
5	75	M	Arteriovenous shunt on the left arm for hemodialysis	37.7	SAPIEN 3; 23 mm
6	84	F	Left SCA and aortic arch; plaque+/stenosis+	47.5	SAPIEN 3; 26 mm
7	90	F	Left SCA; plaque+	36.3	SAPIEN 3; 23 mm
8	89	F	Left SCA; stenosis+/plaque+	33.5	SAPIEN 3; 23 mm
9	85	M	Left SCA; plaque+	30.5	SAPIEN 3; 26 mm
10	82	M	Arteriovenous shunt on the left arm for hemodialysis	41.7	SAPIEN 3; 26 mm
11	87	M	Left SCA; plaque+	62.1	SAPIEN 3; 23 mm
12	89	M	Left SCA; stenosis+/plaque+	41.0	SAPIEN 3; 23 mm
13	87	F	Left SCA; plaque+	71.6	SAPIEN 3; 23 mm
14	80	F	Left SCA; stenosis+/plaque+	60.1	SAPIEN 3; 23 mm
15	84	F	Left SCA; stenosis+/plaque+	53.3	SAPIEN 3; 23 mm
16	80	F	Left SCA; stenosis+/plaque+	56.0	Evolut Pro+; 26 mm
17	80	F	Left SCA; stenosis+/plaque+	61.0	SAPIEN 3; 23 mm
18	82	M	Left SCA; plaque+	45.3	Evolut Pro+; 23 mm
19	84	M	Left SCA; stenosis+/plaque+	62.5	SAPIEN 3; 23 mm
20	84	M	Left SCA; plaque+	40.2	Navitor; 27 mm
21	84	M	Aortic aneurysm of distal arch	41.6	Navitor; 29 mm
22	87	M	Aortic aneurysm of distal arch	39.3	SAPIEN 3; 26 mm

F, female; LtTS, left trans-subclavian; M, male; SCA, subclavian artery; RtTS, right trans-subclavian.

The patients’ characteristics are shown in Table 2. In the RtTS group, the median patient age was 84 (82–87) years and 54.6% of the patients were male. All procedures were performed under general anesthesia for both RtTS and LtTS. Compared with the LtTS group, patients in the RtTS group had higher surgical risk profiles, reflected by a higher Society of Thoracic Surgeons score (10.9%). Fifteen (68%) patients received a SAPIEN 3, and the remaining 7 (32%) patients received an SEV (5 patients received an Evolut Pro+, and 2 received a Navitor), via RtTS access. No patients had a <30° aortic root angle in the RtTS group, and the median aortic root angle was 45.4°, which was not significantly different compared with the LtTS group (P=0.12).

Table 2.

Baseline Patient Characteristics

	RtTS (n=22)	LtTS (n=10)	P value
Age (years)	84 [82–87]	84 [81–91]	0.52
Sex, male	12 (54.6)	4 (40.0)	0.44
BSA	1.5 [1.36–1.52]	1.39 [1.17–1.7]	0.9
LVEF (%)	63 [53–70]	63 [38–66]	0.35
AVA (cm2)	0.77 [0.57–0.83]	0.74 [0.66–0.9]	0.38
BNP (pg/dL)	419 [95.4–1031.9]	454 [61.1–3487.4]	0.16
STS score (%)	10.9 [5.6–15.6]	9.0 [5.2–10.4]	0.33
Hemodialysis	5 (13.2)	3 (30.0)	0.66
Annulus area (cm2)	448 [388–477]	392 [373–463]	0.53
Balloon-expandable valve	15 (68.2)	8 (80.0)	0.48
Aortic root angle (°)	45.4 [40.0–57.0]	54.4 [45.8–62.1]	0.12
Baseline PPM	1 (4.5)	1 (10.0)	0.56
1° AV block	6 (27.7)	3 (30.0)	0.87
CRBBB	3 (13.6)	1 (10.0)	0.76
CLBBB	3 (13.6)	1 (10.0)	0.76

Data presented as n (%), or median [IQR]. AVA, aortic valve area; BNP, B-type natriuretic peptide; BSA, body surface area; CRBBB, complete right bundle branch block; CLBBB, complete left bundle branch block; LtTS, left trans-subclavian; LVEF, left ventricular ejection fraction; PPM, permanent pacemaker; RtTS, right trans-subclavian; STS, Society of Thoracic Surgeons; TF, transfemoral; 1° AV block, first degree atrioventricular block.

Procedural Outcomes and Deployed THV Angle

The mean procedure time for the right subclavian artery was 81.5 min, showing no significant difference compared with the left subclavian artery. The left subclavian artery group tended to have higher bleeding volumes and transfusion requirements due to 1 patient with left subclavian artery access complicated by severe vascular injury; however, no significant difference was observed.

Procedural and 30-day outcomes are presented in Table 3. Successful RtTS access THV deployment was achieved in all patients without valve embolization, incorrect THV position, severe paravalvular leak (PVL), or major vascular complications. Technical success rates were comparable across the groups (LtTS 90%, and RtTS 100%; P=0.95). Two (9.1%) patients had symptomatic stroke in the RtTS group and there were none in the LtTS groups, which did not show a statistically significant difference (P=0.21). Two of the 22 RtTS patients had complicated symptomatic stroke in the RtTS. One female patient required the RtTS due to severe atherosclerosis in the left subclavian artery and aortic arch; however, the right brachiocephalic artery showed minor plaque deposits and tortuosity. She was also on haemodialysis and showed a poor vascular condition. The other patient had only mild calcification in the right subclavian artery, whereas the aortic valve leaflets showed severe calcification. These 2 patients were treated with SAPIEN 3 26 mm and 23 mm respectively.

Table 3.

Clinical and Hemodynamic Outcomes

	RtTS (n=22)	LtTS (n=10)	P value
Procedure time (min)	81.5 [69.8–93.2]	92.6 [54.9–130]	0.43
Intraoperative blood loss (mL)	48.8 [29.5–68.2]	414.3 [−296.1 to 1,124.7]	0.08
Transfusion rate	8 (36.3)	5 (50.0)	0.46
Peak velocity >3.0 m/s	0 (0)	0 (0)	–
Mean PG >20 mmHg	0 (0)	0 (0)	–
Doppler velocity index	0.58 [0.48–0.70]	0.45 [0.40–0.68]	0.80
Effective orifice area (cm2)	1.78 [1.51–1.88]	1.63 [1.26–1.89]	0.79
PVL > mild	2 (9.1)	0 (0)	0.23
Intended performance of the valve	22 (100)	10 (100)	–
Major vascular complication	0 (0)	1 (10.0)	0.12
PPI	0 (0)	0 (0)	–
Symptomatic stroke	2 (9.1)	0 (0)	0.21
30-Day all-cause mortality	1 (4.5)	0 (0)	0.37
Device success at 30 days	21 (95.4)	9 (90)	0.57

Data are presented as n (%), or median [IQR]. PG, pressure gradient; PPI, permanent pacemaker implantation; PVL, paravalvular leak. Other abbreviations as in Table 2.

New PPI was not required in any of the patients in the RtTS and LtTS groups. One RtTS patient had a pre-existing pacemaker implantation. Of the 21 patients, 3 (14.2%) had CRBBB and 6 (28.5%) had a history of AV block, while none required a new pacemaker implantation after RtTS TAVI. One patient died of non-occlusive mesenteric ischemia within 30 days of the procedure in the RtTS group. Thirty-day mortality did not differ significantly among the groups (P=0.66).

The RtTS group had significantly higher angles compared with the other LtTS groups (LtTS: 6.0° [0.6–8.9], and RtTS: 8.7° [4.4–11.6]; P<0.05). There was no significant difference in THV depth on the NCC side in each group, whereas the RtTS group had significantly deeper implantation on the LCC side compared with the LtTS groups (LtTS 2.4 [−0.2–5.2] mm, and RtTS 4.4 [2.1–7.8] mm; P<0.01; Figure 3).

Figure 3.

Transcatheter heart valve (THV) angle (A) and depth (B) with the transfemoral, left trans-subclavian (LtTS), and right trans-subclavian (RtTS) approaches in transcatheter aortic valve implantation.

There were no significant differences in post-procedural echocardiographic parameters, including effective orifice area and mean pressure gradient. All RtTS patients achieved the intended valve performance (i.e., peak velocity <3.0 m/s, mean pressure gradient <20 mmHg, and DVI >0.25) without > moderate PVL. Device success, including 30-day mortality, did not differ significantly between the groups (LtTS 90%, and RtTS 95.4%; P=0.57).

Subgroup Analysis by Valve Type in the RtTS Group

In the RtTS group, a BEV was used in 15 (68%) patients and an SEV was used in 7 (32%) patients. BEV use was associated with larger device–annulus angles compared with SEV use (7.6° vs. 11.6°, respectively; P=0.01). However, technical success was achieved in all cases, and device success at 30 days did not differ significantly between the valve types. Procedural success, THV function, and clinical outcomes also did not differ significantly between the valve types (Table 4).

Table 4.

Subgroup Analysis by Valve Type in the RtTS Group

	BEV (n=15; 68%)	SEV (n=7; 32%)	P value
Device-annulus angle (°)	7.6 (3.4–11.1)	11.6 (7.8–16.6)	0.01
Intended performance of the valve	15 (100)	7 (100)	–
Peak velocity >3.0 m/s	0 (0)	0 (0)	–
Mean PG >20 mmHg	0 (0)	0 (0)	–
Device success	14 (93)	7 (100)	0.48

Data are presented as n (%), or median [IQR]. BEV, balloon-expandable valve; PG, pressure gradient; RtTS, right trans-subclavian; SEV, self-expanding valve.

Discussion

This study demonstrated that despite inherent anatomical challenges in RtTS, such as poor coaxiality of the THV within the aortic annulus, procedural success and THV performance were comparable with those of the LtTS or TF access routes.

As TAVI has become more common for aortic stenosis, surgical access approaches (e.g., transapical or transaortic) have declined, and less invasive subclavian/brachiocephalic or carotid artery access has increased. A report from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry on non-TF access with the SAPIEN 3 BEV stated that transaxillary (TAx)/TS access was used in 20% of non-TF cases in 2015 and that the rate increased to 49% in 2017.¹⁰ Furthermore, TS access has a better 1-year prognosis than that with transapical or TAo access, and equivalent procedural and mid-term outcomes to those of TF access.^11–13 On the basis of these data, TS access is a reasonable, less-invasive alternative to TF access, if stroke risk is carefully considered.

LtTS is a highly favored access alternative to TF because of device system coaxiality to the aortic root angle. In contrast, RtTS is used less often because of poor device coaxiality leading to technical difficulty during the procedure. An Italian multicenter retrospective study of 141 patients with TS/TAx access published in 2012 reported that only 6 (4%) patients underwent RtTS access and that the left side was used in the vast majority of patients. Single-center reports indicate that RtTS access is used in approximately 14–15% of cases.^14,15

The anatomical indication criteria for the right subclavian artery approach, valve selection, and choice of alternative access approaches vary widely between centers. A major reason for less use of the right subclavian artery for SEV placement is the recommendation for an aortic root angle of <30°. In the present study, we did not limit the angulation of the aortic root angle for RtTS for SEV placement. In fact, there were no cases in which the angle was <30°, and the median angle was 45.7°.

A study of 10 cases of RtTS access using a first-generation SEV reported that mortality, PVL, vascular complications, and stroke rates did not differ significantly from those with LtTS access.¹⁵ The authors also reported no moderate or severe PVL, similar to the findings in our study. Implantation of a SEV via RtTS access is considered technically challenging because of the greater valve tilt width. However, as stated earlier, SEVs tilt with valve release but can be implanted if the device height is aligned with the NCC as the starting point. In this report, THV migration, moderate-to-severe PVL, and a second valve was not documented.

There are even fewer studies on the outcomes of BEV implantation with RtTS than those with SEV implantation. McGrath et al. reported the outcomes of BEV implantation in 25 patients who underwent RtTS compared with LtTS.¹⁶ The study found no difference in predominance between the approaches. To improve the coaxiality of the THV to the aortic annulus, Zhan et al. described 10 cases of the flip-n-flex technique with a BEV and reported good short-term outcomes with no > mild PVL or 30-day mortality.¹⁷ In our study, 15 patients were treated with a SAPIEN 3 via RtTS access, and similar results were obtained without using the flip-n-flex technique. Our implantation method involves no additional manipulation. In simple terms, the bottom of the NCC is used as a marker to start the implantation depth, and the THV naturally moves toward coaxiality. As a result, despite the misaligned device angle, valve function was favorable and no > moderate PVL was observed.

Another concern with RtTS TAVI is the high incidence of PVL and poor valve function because of the lack of coaxiality. We evaluated the angle of the implanted device relative to the annular plane, and found that neither SEVs nor BEVs actually maintain coaxiality with RtTS access. In particular, SEVs remained predominantly tilted at 11.6° compared with an angle of 7.6° with BEVs. However, with RtTS, valve function, including PVL, was comparable with that with TF access.

The reported incidence of new PPI with the TAx or TS approach ranges from 11% to 23%,^10,14,18 whereas our study showed no new PPI with RtTS. A possible reason for this difference is that our starting device implantation position was the bottom of the NCC, which may explain the very shallow NCC side THV positioning and no conduction disturbances.

In this study, the stroke rate was significantly higher with RtTS compared with LtTS. The predictors of stroke are advanced age, renal failure, and previous stroke history.^19–21 In the present study, 13% of patients in the RtTS group were receiving hemodialysis and had a predominantly higher Society of Thoracic Surgeons score, indicating that the RtTS group included patients with poor vessel status who cannot undergo the TF and LtTS approaches. Another consideration is the anatomical characteristics of RtTS, in which the device passes through the bifurcation of both the common carotid and vertebral arteries; therefore, patients who undergo RtTS may be vulnerable to cerebrovascular injury. In fact, a study comparing left and right radial artery access percutaneous coronary intervention has reported a higher incidence of in-hospital stroke with right radial artery access.²² A similar mechanism may be applicable in RtTS TAVI. The risk of stroke with subclavian artery access can be avoided if device placement is performed correctly.

Study Limitations

Several limitations must be acknowledged in our study. First, the single-center, retrospective design limits the generalizability of our results and introduced inherent selection and information biases. Second, the sample size in the RtTS group was small; only 22 patients underwent TAVI, limiting the statistical power to detect differences in rare events. Third, imaging analysis was performed using angiography, and 3-dimensional CT imaging might provide more precise measurements. Last, this study lacks long-term follow-up data. Studies of long-term durability and the clinical outcomes are required.

Conclusions

RtTS access is a feasible and effective alternative to LtTS for TAVI in patients unsuitable for TF access, providing comparable procedural success and THV performance despite anatomical challenges. However, the increased risk of stroke necessitates caution, emphasizing the importance of patient selection. Further studies with larger cohorts are warranted to validate our findings and refine procedural strategies for RtTS TAVI.

Disclosures

G.N. is a proctor for Edwards (SAPIEN), Medtronic (Evolut), and Abbott (Navitor). The other authors have no conflicts of interest to declare.

IRB Information

The present study was approved by Ethics Committee of Kindai University Hospital (reference no. R03-040).

Data Availability

The deidentified participant data will not be shared.