Transcatheter bicuspid aortic valve replacement in Turner syndrome: A unique experience of interventional cardiologist

Abstract

A 69-year-old short-statured Turner syndrome (TS) patient with a history of poliomyelitis in childhood and moderate bicuspid aortic stenosis (BAS) reported worsening dyspnea and fatigue over six months. A repeat transthoracic echocardiogram revealed progression to severe aortic stenosis with dilated ascending aorta (AA). As part of the work-up for aortic valve replacement, the patient underwent cardiac catheterization, which revealed a severely calcified AV with an area of 0.5 sq. cm and a mean gradient of 37 mmHg. On coronary angiography, there was 70% stenosis of the proximal left anterior descending artery (LAD). Due to poor rehabilitation potential, she was deemed high-risk for surgical aortic valve replacement. A recommendation for transcatheter aortic valve replacement (TAVR) with stenting of the proximal LAD was made. Dilated AA was managed conservatively with serial noninvasive imaging. The patient underwent TAVR with Edwards-Sapien valve (23 mm S3) and stenting of proximal LAD. The procedure was successful without complications. To our knowledge, our patient is the first case of TAVR in BAS with aortopathy in TS.

<Learning objective: Therapeutically, transcatheter aortic valve replacement is an off-label indication for bicuspid aortic stenosis. In real-life practice, many of these patients are poor surgical candidates and demand careful and judicious decision-making in the presence of diverse clinical scenarios. In such circumstances, a multidisciplinary approach with shared decision-making is required to recommend best possible therapeutic solution in the presence of limited data.>

Introduction

Turner syndrome (TS) patients bear several cardiovascular malformations such as bicuspid aortic valve (BAV), dilatation or dissection of ascending aorta (AA), and coarctation of the aorta [1], which can make cardiac interventions challenging. Consequently, severe aortic stenosis (AS) with bicuspid morphology in TS offers a unique therapeutic challenge to the interventional cardiologist and portends an additional risk compared to non-Turner patients due to coexisting aortopathy and coarctation. Furthermore, the aortopathy has variable severity ranging from mild to aneurysmal dilation or dissection with consequent rupture, which needs to be considered when intervention is required [2], [3].

Surgical replacement, although the first line in bicuspid aortic stenosis (BAS), is not feasible in many real-life scenarios due to the complexity of clinical picture, comorbidities, and operative risk. In these circumstances, a high surgical-risk candidate might require a nonsurgical intervention such as transcatheter aortic valve replacement (TAVR). In the recent past, the performance of TAVR in tricuspid aortic valve stenosis (TAS) was considered a novel technology in poor surgical candidates. However, a rapidly-proliferating body of evidence supported its safety and efficacy and made TAVR the standard of care in inoperable cases. Until recently, published data regarding TAVR in BAS were insufficient, relying mainly on a few case series. However now, more comparative data are becoming available. In a recent study, the outcomes of TAVR in BAS versus TAS were compared. The data demonstrated TAVR as an effective and safe option in BAS. The overall prognosis and all-cause mortality after two years were similar in both the groups with fewer device failure rates in TAS [4].

Although this evidence could be convincing for using TAVR in BAS, the unique clinical context of TS with existing aortopathy and comorbidities makes therapeutic decision-making challenging. To our knowledge, there are no cases reported on TAVR in TS patients with BAS. We present a case of TS with BAS who underwent TAVR being a poor surgical candidate.

Case report

A 69-year-old short-statured (height: 1.4 m, body mass index: 36.94) female with TS was being followed as an outpatient for her moderate BAS. She had a prior history of hypertension, diabetes mellitus, obstructive sleep apnea, and hyperlipidemia. Over a six-month period, the patient reported progressive exertional dyspnea and extreme fatigue, which was interfering with her daily activities. She had poliomyelitis in her childhood, which led to the paralysis of her left leg requiring a knee brace. She had difficulty in walking at baseline due to her asymmetric gait and needed a walker for ambulation. Later, she developed significant hip arthritis requiring hip joint replacement. She had a history of palpitations, which on evaluation with a Holter monitor showed frequent premature atrial and ventricular complexes in addition to one brief episode of supraventricular tachycardia. There was no prior history of other arrhythmias including atrial fibrillation. Physical examination showed a grade II/VI soft ejection systolic murmur at the aortic area with a soft second heart sound; cardiac rhythm was regular. Neurologically, her left lower extremity was paralyzed due to poliomyelitis. On transthoracic echocardiogram (TTE), the patient had progressed to severe AS with a valve area of 0.5 sq. cm, AV velocity of 4.1 m/s, and a mean gradient of 39 mmHg. Ejection fraction was 60% with grade II diastolic dysfunction. Additionally, there was enlargement of the aortic root (4.3 cm), severe bi-atrial enlargement, and mild pulmonary hypertension with a right ventricular systolic pressure of 40 mmHg. There was mild mitral and tricuspid regurgitation. No specific cause of severe bi-atrial enlargement could be ascertained apart from diastolic dysfunction and pulmonary hypertension.

Given her severe, symptomatic AS, she was referred for AV replacement.

For further work-up, the patient underwent cardiac catheterization which revealed a severely calcified AV with an area of 0.5 sq. cm and a mean gradient of 37 mmHg; AA was moderately dilated. On coronary angiography, there was a 70% stenosis of the proximal left anterior descending artery (LAD). Computed tomography angiogram (CTA) was performed to delineate the aortic root anatomy and iliofemoral vasculature, which showed a dilated AA measuring 4.3 × 4.3 cm without dissection (Fig. 1, Fig. 2). The aortic valve was bicuspid with significant calcification of one of the leaflets (Fig. 3).

Fig. 1.

Computed tomography angiogram displaying double-oblique projections along the aortic root axis from multiplanar reconstruction showing: (A) calcification on the bicuspid aortic valve along with dilated ascending aorta; (B) elucidation of the angle between ascending aorta and the plane of the bicuspid aortic valve.

AA, ascending aorta; RA, right atrium; LV, left ventricle; PA, pulmonary artery.

Fig. 2.

(A) Computed tomography angiogram displaying a double-oblique projection of the aorta from multiplanar reconstruction showing dilated ascending aorta, 90° angle in the arch at the junction of the transverse and descending aorta (arrow) and tortuosity in the descending thoracic aorta. (B) 3D reformatted angiogram of the aorta showing the above abnormalities.

AA, ascending aorta; DA, descending aorta.

Fig. 3.

Computed tomography angiogram displaying double-oblique projection along the bicuspid aortic valve annular plane from multiplanar reconstruction showing asymmetric calcification of the aortic leaflets.

RA, right atrium; LA, left atrium; PA, pulmonary artery; BAV, bicuspid aortic valve.

Following cardiac catheterization, the patient’s case was presented in the multidisciplinary valve conference. The options of surgical aortic valve replacement (SAVR) with single-vessel bypass and possible aortic root replacement versus TAVR with stenting of the proximal LAD were discussed in detail.

Based on the Society of Thoracic Surgeons (STS) score, the risk of morbidity and mortality for SAVR was 14% in her case. Furthermore, due to short stature, frailty, and physical disability due to polio, her rehabilitation potential was considered poor by a cardiothoracic surgeon, and she was deemed high-risk for SAVR, coronary artery bypass surgery, and aortic root replacement. Therefore, a recommendation was made to stent the proximal LAD and proceed with TAVR for severe AS. The patient agreed and underwent TAVR with a drug-eluting stent to the proximal LAD in the same setting. (Fig. 4).

Fig. 4.

Cine angiogram during positioning and deployment of the Edwards Sapien S3 valve. (A) Alignment and positioning of the valve using the advantage of the flexible sheath. (B) Deployment of the valve and annular fixation by balloon inflation. (C) Post valve-deployment image.

Her AA, although dilated, was not considered imminently life-threatening and hence a conservative approach with serial noninvasive testing was recommended especially expecting the possibility of aortic root stabilization after AV replacement.

Several anatomic factors were carefully evaluated in pre-procedural planning for TAVR in this patient for reducing the chances of maldeployment, paravalvular leak (PVL), and vascular complications. The factor most technically challenging was a less than 90° angle between the annular plane of the BAV and the long axis of the AA (Fig. 1). Moreover, due to asymmetric dense linear calcifications on one of the leaflets of the BAV, there were increased chances of suboptimal seal and PVL. The aortic arch had a sharp 90° angle at the junction of the arch with the descending aorta, which was also tortuous (Fig. 2). Additionally, the access vessels were small and tortuous with increased chances of bleeding and vascular complications. To facilitate implant planning, sizing and choice of the transcatheter valve, a 3D reconstruction of the aortic root was achieved from CTA gated to electrocardiogram at 41% and 71% phase at a slice thickness of 600 μm using the 3mensio^R software (Bilthoven, the Netherlands).

At the time of the procedure, Medtronic’s CoreValve (Medtronic Inc., Galway, Ireland) and Edwards-Sapien S3 (Edwards Lifesciences, Irvine, California, USA) were the only two commercially-available valves; new-generation Evolute-R (Medtronic Inc., Galway, Ireland), Evolute-Pro (Medtronic Inc., Galway, Ireland), and Lotus (Boston Scientific Corporation, Natick, Massachusetts, USA) were unavailable. Both the available valves were evaluated in regards to the patient’s anatomy. The annulus area and perimeter were measured at 400.7 mm² and 71.5 mm, respectively. Desirable features of the implant, in this case, were (1) ability to flex the delivery sheath to negotiate the unusual aortic arch and to align the valve to the challenging angle of the annulus, (2) primary annular fixation without AA attachment to avoid its influence on valve alignment, and (3) the presence of a sealing skirt to prevent PVL in an asymmetrically calcified BAV. Considering these factors, a 23 mm Edwards-Sapien S3 valve was chosen in her case due to the low profile, ability to flex the delivery mechanism, and presence of a sealing skirt. The size of the valve was determined based upon CT measurements of the annulus.

The patient’s proximal LAD was stented with a drug-eluting Xience stent (Abbot Vascular, Santa Clara, California, USA) before transcatheter valve implantation in the same setting. The pre-procedure mean gradient of 43 mmHg was reduced to 3 mmHg post-TAVR. After the deployment of Edwards-Sapien S3 valve, a subsequent aortography revealed trace paravalvular regurgitation.

The patient tolerated the procedure well and was started on dual antiplatelet therapy for six months.

Three weeks after the procedure, she had a follow-up visit and reported significant improvement in her fatigue and exertional dyspnea. Later, three months after TAVR, a TTE was performed which revealed Edwards-Sapien bioprosthetic AV with mean AV gradient of 14.6 mmHg and trivial paravalvular AV regurgitation.

The patient continued to improve on subsequent visits and denied new complaints.

Discussion

Although it seems straightforward to proceed with transcatheter replacement for a TAS in nonsurgical candidates, it becomes challenging to choose TAVR in a similar patient with BAV especially with aortic root dilatation and demands experience, discussion, and consensus among various members of a multidisciplinary team. TAVR for BAV remains an off-label indication and carries a higher risk of paravalvular regurgitation [5].

Moreover, there is an additional risk of malpositioning, maldeployment, and malexpansion of the transcatheter AV prosthesis due to asymmetric, excessively calcified larger annulus of BAV [5].

Despite these facts, review of the literature reveals several patients who underwent successful TAVR for BAV stenosis and showed satisfactory clinical progress [6].

In addition to the previously available data, a recent study comparing the outcomes of TAVR in BAS versus TAS found no significant difference in terms of prognosis and all-cause mortality (17.2% versus 19.4%, p-value of 0.28) in both the groups. However, regarding procedure-related outcomes, patients with BAS were at greater risk of having conversions to surgery (2% versus 0.2%, p-value of 0.006), aortic root injury (1.6% versus 0.0%, p-value of 0.004), implantation of 2 valves (4.8% versus 1.5%, p-value of 0.002), and PVL (10.4% versus 6.8%, p-value of 0.04) compared with TAS. Device success rate was also lower in BAS compared with TAS (85.3% versus 91.4%, p-value of 0.002). But overall this study supported the use of TAVR in BAS, especially using new-generation devices due to their lower rates of complications [4]. In our patient, Edwards-Sapien 3 valve, a new-generation valve, was chosen due to less chance of PVL and malpositioning based upon patient’s anatomy. Regarding the CoreValve, there was a concern that it would deploy shallowly at the non-coronary cusp and deeply at left coronary cusp due to the angle of the annular plane, leading to maldeployment and PVL. Evolute-R, Evolute-Pro, and Lotus valves if commercially available at that time would have provided some advantage in terms of recapturability and presence of a sealing skirt.

Recently, one study preferred the use of new-generation devices (Sapien 3 and Lotus) compared with early-generation devices (Sapien XT and CoreValve) based on their comparison of various clinical and procedure-related outcomes. Furthermore, they reported fewer complications (aortic root rupture, PVL, and second valve implantation) associated with new-generation devices [7]. In our case, we were able to successfully implant a new-generation device (Edwards-Sapien S3) in a challenging anatomy, making use of the design advancements.

Although we could not find published cases of TS with BAS who underwent TAVR, Nascimbene et al. recently reported a 31-year old TS-patient with unicuspid AV who successfully underwent TAVR, being inoperable due to severe pulmonary hypertension and multiple comorbidities. She was treated with 20 mm of Edwards-Sapien 3 valve matching with her annular size and showed no evidence of post-deployment aortic insufficiency. Although the procedure was short-timed and had no significant complications, the patient required a lengthier hospital stay and extended acute care due to her complicated clinical profile [8]. In contrast to this patient, our patient recovered earlier and had a limited hospital stay.

Based on our experience with this patient, we propose that in high surgical-risk TS-patients with multiple anatomic and clinical comorbidities, TAVR offers a viable therapeutic alternative and hence should be considered when options are limited.

Although BAS remains an off-label use for TAVR, not all the patients are surgical candidates in real-life practice and often present with diverse clinical scenarios. In such circumstances, a multidisciplinary approach with a shared decision-making can broaden the procedural options and provide a therapeutic solution in selective cases especially when the data are limited, and evidence is scarce or evolving.

Conflict of interest

There is no conflict of interest.