Trans-catheter aortic valve-in-valve implantation in an elderly patient with Evans syndrome

Abstract

We report the first case of trans-catheter aortic valve implantation in a 90-year-old man with a severely stenotic bioprosthetic aortic valve in the context of an autoimmune hemolytic anemia and immune thrombocytopenia (Evans syndrome) using the trans-femoral approach. The patient was supported in the peri-procedural period with high-dose steroids, intravenous immunoglobulins, platelet transfusions, and thrombopoietin receptor agonist (romiplostim). The post-procedural period was unremarkable with no bleeding complications.

<Learning objective: Trans-catheter aortic valve implantation has become a treatment option for severe aortic stenosis in patients with high-risk features for surgical intervention. This includes patients with bleeding diathesis, who can undergo trans-catheter aortic valve replacement with minimal incidence of vascular and bleeding complications with careful peri-procedural planning using current standard of care approaches.>

Introduction

Aortic stenosis is a clinical entity with a long latency period followed by rapid progression after the appearance of symptoms [1]. Sudden cardiac death affects 8–34% of patients with symptomatic severe aortic stenosis [2]; hence, prompt valve replacement is generally recommended [3]. Surgical replacement is the treatment of choice and is associated with low operative mortality in the absence of significant co-existing medical conditions [4]. However, between 33% and 41% of patients with severe symptomatic aortic stenosis are at a prohibitive risk for surgical intervention due to underlying co-morbidities [5].

Trans-catheter aortic valve implantation (TAVI) offers a minimally invasive route for the management of severe, symptomatic aortic stenosis in patients who are at high operative risk. In addition, trans-catheter valvular implantation has been feasible in patients with failed surgically implanted bioprosthesis (valve-in-valve TAVI) [6], thereby avoiding the increased complication rates in surgical re-operation. However, vascular complications, due to the use of large-diameter catheters and underlying high-risk characteristics of the population, have been associated with unfavorable clinical outcomes and increased long-term mortality [7]. Herein we describe our experience in the peri-operative management of the first reported case of valve-in-valve TAVI in a patient with Evans syndrome (a rare syndrome of combined autoimmune hemolytic anemia and immune thrombocytopenia).

Case report

A 90-year-old man, with known hypertension, hypercholesterolemia, and chronic renal insufficiency, who had undergone surgical aortic valve replacement with a 23-mm porcine aortic valve 11 years previously for severe non-rheumatic aortic stenosis (Carpentier-Edwards Aortic valve Model: 2625, Edwards Lifesciences Inc., Irvine, CA, USA; Fig. 1), was the case study. The patient presented to our hospital with three months history of progressive decline in exercise tolerance, worsening dyspnea on exertion, and was found to have a severely obstructed aortic valve prosthesis on echocardiography (aortic valve area was 0.8 cm², aortic valve area index was 0.4 cm²/m², mean gradient was 50 mmHg, and peak gradient was 82 mmHg). Ventricular function was severely reduced (left ventricular ejection fraction of 30–35%) with mild aortic and mitral insufficiency.

Fig. 1.

Illustration of the dimensions of the previously placed 23-mm Carpentier-Edwards surgical bioprosthesis (model: 2625 Aortic). Reproduced with permission from Edwards Lifesciences Inc., Irvine, CA, USA. A: Mounting diameter (annulus) = 23 mm, B: Graft mounting diameter (stent I.D.) = 21 mm, C: Profile height = 20 mm, D: External sewing ring diameter = 29 mm.

On presentation, the patient developed volume overload and was admitted to the coronary care unit for hemodynamic instability requiring inotrope and vasopressor support. Admission laboratory results were remarkable for acute chronic renal insufficiency (blood urea nitrogen 51 mg/dL and creatinine 1.9 mg/dL), normal transaminases and bilirubin levels, normocytic anemia (hemoglobin 9.5 g/dL, mean corpuscular volume 90.2 fL, red cell distance width 17.6%), thrombocytopenia (platelet count 64 × 10³/μL), a normal white blood cell count, and within-range coagulation profile. Chest X-ray was consistent with pulmonary edema. The patient subsequently improved with diuresis and non-invasive positive pressure ventilation. Coronary angiography showed non-obstructive coronary artery disease and right heart catheterization showed normal pulmonary pressures.

The patient denied any history of bleeding diathesis. Previous laboratory findings were remarkable for a normal complete blood count during the peri-operative period of the aortic valve surgery, 11 years previously (with no subsequent blood work). The patient's home medications included aspirin, metoprolol, lisinopril, and allopurinol. The patient reported taking no herbal supplements or over-the-counter medications. Subsequent blood work revealed a low haptoglobin level (less than 15 mg/dL), a mildly elevated lactate dehydrogenase level (LDH, 259 IU/L), an elevated absolute reticulocyte count (157 × 10³/μL), a positive direct Coombs test, and a blood smear showing marked anisocytosis, poikilocytosis, polychromasia, tear drop cells, spherocytosis, burr cells, occasional schistocytes with decreased platelets, and occasional large and giant platelets. The patient was diagnosed with Evans syndrome, given the occurrence of two hematologic immune cytopenias, Coombs-positive autoimmune hemolytic anemia and immune thrombocytopenia, and the exclusion of other immune disorders.

In preparation for the TAVI, the patient was continued on high-dose steroids (hydrocortisone 100 mg TID – started initially in the setting of hemodynamic instability prior to the diagnosis of Evans syndrome). The patient was also given 2 g/kg of intravenous immunoglobulins with no improvement in platelet count (count dropped from 64 × 10³/μL to 29 × 10³/μL). The patient received multiple platelet transfusions, and underwent a trans-femoral aortic valve implantation while having a platelet count of 61 × 10³/μL. The 6-Fr and 7-Fr sheaths were placed in the right femoral vein and right femoral artery, respectively. A 16-Fr Edwards e-sheath was inserted into the left femoral artery under fluoroscopy following pre-placement of two Perclose devices (Abbott, Abbott Park, IL, USA). A 23-mm Edwards Sapien XT was then advanced across the aortic valve following a 20-mm Edwards valvuloplasty balloon. After confirmation of position by aortography and trans-esophageal echocardiography, the valve was successfully deployed during right ventricular pacing at 170 bpm (Fig. 2, Fig. 3). After valve deployment, trans-esophageal echocardiography confirmed the absence of central and para-valvular aortic regurgitation and revealed a 21-mmHg mean gradient across the new aortic valve. The access was closed with the pre-positioned Perclose devices. The right femoral vein temporary pacer was removed. The patient was hemodynamically stable and was extubated in the catheterization laboratory post-procedure.

Fig. 2.

Still frame of intra-operative trans-esophageal echocardiography showing position of the Sapien valve across the stenotic bioprosthetic valve (orange arrow) with the 0.035 in Lunderquist wire across the valve (red arrow).

Fig. 3.

Fluoroscopic image showing inflation and deployment of the balloon expandable Edwards Sapient XT valve during right ventricular pacing at 170 bpm, with the Lunderquist wire across the aortic valve.

Post-procedurally, the patient was not started on anti-platelet therapy. He was continued on high-dose steroid therapy but the platelet count continued to downtrend, so he was given one dose of romiplostim 1 mcg/kg and supported with platelet transfusions. There was no evidence of access site or non-access site bleeding. The patient was subsequently discharged to a rehabilitation facility with plans for close follow-up with hematology for further thrombopoietin receptor agonist therapy. At 1-month follow-up, the patient reported significant improvement in exercise tolerance and exertional symptoms. There were no bleeding issues and the platelet count had recovered to 127 × 10³/μL. Repeat trans-thoracic echocardiography showed improved left ventricular function (ejection fraction of 63%) and a functional bioprosthetic aortic valve with no significant stenosis or regurgitation (aortic valve area was 1.4 cm², aortic valve area index was 0.7 cm²/m², and mean gradient was 24 mmHg).

Discussion

Valvular aortic stenosis represents a commonly encountered clinical disorder with significant mortality once symptoms occur. TAVI offers an outlet in patients who are at prohibitive risk for surgical intervention due to multiple pre-existing medical conditions, especially in this patient with pre-existing immune thrombocytopenia where surgical morbidity and mortality would be significantly high. This article describes the first reported case of TAVI in an elderly patient with the rare hematological condition of Evans syndrome.

Thrombocytopenia following TAVI is frequent but is of an unknown etiology in the general population [8]. Furthermore, patients with pre-existing thrombocytopenia have been described to be at risk for worse in-hospital outcomes. Flaherty et al. [9] described the in-hospital clinical outcomes in 36 patients with pre-procedural, pre-existing thrombocytopenia in patients undergoing TAVI. Pre-existing pre-TAVI thrombocytopenia was associated with a statistically significant increased risk of vascular complications (53%), major bleeding (42%), and requirement for red blood cell transfusions (75%). In addition, data from the Placement of AoRTic TraNscathetER Valve trial (PARTNER) have shown increased long-term mortality with major vascular complications [7]. Our patient, who was diagnosed with an autoimmune hemolytic anemia and immune thrombocytopenia, required high-dose steroid therapy, intravenous immunoglobulin therapy, and multiple platelet transfusions to achieve a platelet count of >50 × 10³/μL in the peri-operative period. It is unknown whether he had primary or secondary Evans syndrome, as serological tests for a myeloproliferative disorder were unrevealing but the patient refused a bone marrow biopsy for further evaluation. Moreover, since Evans syndrome is such a rare clinical entity, there have been no prospective or randomized-controlled clinical trials, and as a result, the management of Evans syndrome is based on empirical data, mainly from indirect evidence extrapolated from the standard treatment of primary idiopathic thrombocytopenia or autoimmune hemolytic anemia.

In conclusion, the successful performance of a trans-femoral trans-catheter aortic valve-in-valve implantation, the first to be described in a patient with Evans syndrome, attests to the considerable advantages offered by TAVI over surgical intervention in patients with serious pre-existing bleeding diathesis. Through meticulous technique and careful peri-procedural planning, vascular and bleeding complications can be avoided and managed with current standard approaches in these rare high-risk patients who otherwise may not have a viable and safe alternative for repeat valve replacement prior to the TAVI era.

Sources of funding

No funding was required to support this publication.

Conflicts of interests

The authors report no financial relationships or conflicts of interest regarding the content herein.