Reversal of angiodysplasia-derived anemia after transcatheter aortic valve implantation

Summary

Aortic valve stenosis associated with angiodysplasia (Heyde's syndrome) and consequent anemia had previously been reported to benefit from surgical aortic valve replacement. In this clinical case an 89-year-old patient with chronic angiodysplasia-derived anemia, characterized by acute phases of active gastrointestinal bleeding experienced a normalization of hemoglobin values after a trans-catheter aortic valve implantation (TAVI) of a self-expandable aortic valve prosthesis (CoreValve, Medtronic Inc., Minneapolis, MN, USA). This is the first, to our knowledge, reported clinical case of remission of angiodysplasia-derived anemia after TAVI.

Introduction

Severe aortic valve stenosis can be complicated by gastrointestinal angiodysplasia (Heyde's syndrome) [1], a hemorrhagic syndrome associated with acquired type 2A von Willebrand disease, characterized by the loss of the largest multimers of von Willebrand factor (vWF) [2], [3], [4], [5]. vWF abnormalities were previously found to be directly related to the severity of aortic stenosis [6], while clinical improvements were reported after surgical valve replacement [7], [8].

Most recently, transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement (SAVR) for patients with symptomatic severe aortic stenosis considered to be at very high or prohibitive operative risk [9], [10], [11], [12], [13], [14]. Currently, there are no reported cases of remission of gastrointestinal angiodysplasia following TAVI.

Case description

An 89-year-old female patient with hypertension, peripheral arterial vascular disease, and previous episodes of transient ischemic attack was admitted to our Cardiovascular Department with acute pulmonary edema.

During the previous three years she underwent repeated hospital admissions for syncope and exertional angina. Transthoracic Doppler echocardiography showed a severe aortic stenosis. SAVR was proposed to the patient, which she refused and was discharged on optimal drug treatment. Moreover, during the previous year she was repeatedly admitted to the Internal Medicine Department for ematemesis and melena; the patient underwent an esophagogastroduodenoscopy during acute anemization [hemoglobin (Hb) 8.6 g/dl] that demonstrated active bleeding lesions compatible with gastrointestinal angiodysplasia (Fig. 1). She underwent a colonoscopy, which also showed intestinal angiodysplasic lesions. All other alternative causes of bleeding were excluded. The patient was treated with perendoscopic plasma coagulation, blood transfusions, and proton-pump inhibitors and the Hb levels were stabilized at 10 g/dl approximately. The blood count was consistent with acute anemization superimposed on chronic sideropenic anemia. The platelet count was normal in all the consecutive determinations. Considering the former diagnosis of severe aortic stenosis, a Heyde's syndrome diagnosis was made.

Figure 1.

Endoscopic view of gastric angiodysplasia, hemorrhagic lesion.

At admission in our department, the patient had electrocardiographic evidence of anteriorlateral subepicardial ischemia, but troponin I levels were normal. Diffuse anterolateral ST segment alterations were observed at the telemetric monitoring of the patient during angina. Other laboratory exams documented a Hb value of 11.1 g/dl, a platelet count of 166,000/mm³, and evidence of sideropenic anemia. B-natriuretic peptide was 657 pg/ml. The transthoracic Doppler echocardiographic evaluation demonstrated a normal left ventricular (LV) systolic function (LV ejection fraction 60% – Simpson biplane method), a mild and homogeneous LV hypertrophy and confirmed the severity of the aortic stenosis (aortic valve area measured by continuity equation 0.56 cm²; mean and maximum pressure gradient 44 and 73 mmHg, respectively).

The patient was evaluated by our Department Heart Team (heart surgeon–interventionist–clinical cardiologist). Logistic Euroscore and Society of Thoracic Surgeons score were 32.2% and 10.3%, respectively. Considering the patient's will and the relatively high surgical risk, a TAVI procedure was proposed and accepted by the patient. Pre-TAVI angiographic coronary evaluation demonstrated a proximal and medial left anterior descending (LAD) artery disease (stenosis of 60% and 90%, respectively), an anatomically critical proximal circumflex stenosis (80%) and a 70% stenosis of the medial and distal segment of the right coronary artery.

The patient had no echocardiographic evidence of systolic dysfunction and also kinetical alteration of segmental wall movement were never observed. Diffuse anterolateral ST segment alteration was observed at the telemetric monitoring of the patient during angina; therefore we chose a conservative approach by treating only the LAD.

A percutaneous transcatheter coronary angioplasty was performed on medial LAD with bare metal stent implantation (Medtronic Driver 3 mm × 15 mm, Medtronic Inc., Minneapolis, MN, USA). An angiography of the iliac and femoral arteries was performed after the end of the interventional procedure, showing absence of critical stenosis. A transesophageal bidimensional echocardiography was also performed, which measured an aortic annulus of 23 mm.

A transfemoral approach was decided on the basis of the angiographic and echocardiographic findings. The patient underwent balloon aortic valvuloplasty and transcatheter aortic valve implantation with CoreValve n.26 (Medtronic) (Fig. 2).

Figure 2.

Implanted CoreValve (end of the procedure of the transcatheter aortic valve implantation).

The procedure was complicated by the occlusion of the left common femoral artery, which was successfully treated with percutaneous angioplasty and stent implantation. The immediate post-TAVI echocardiography showed a complete remission of the trans-aortic pressure gradient, with moderate aortic regurgitation. The patient remained asymptomatic during the following days and was discharged 3 days after the procedure.

During follow up, the patient was asymptomatic for angina. The clinical evaluation did not reveal signs of heart failure. The aortic regurgitation remained moderate at echocardiography six months after TAVI. Serial laboratory evaluations documented a normalization of the Hb at 13.3 g/dl, no further acute anemization, and normal hemosiderin and transferrin levels. Platelet count was normal in all the determinations and the patient did not further suffer from gastrointestinal bleeding.

Discussion

Heyde's syndrome was previously defined as the association between aortic stenosis and gastrointestinal angiodysplasia [1]. Previous studies verified this association and hypothesized a causative mechanism implying the vWF [6]. Highest-molecular multimers of vWF are cleaved by ADAMTS-13, a metalloprotease, in the presence of elevated shear stress, such as in aortic stenosis [15]. This interaction results in the phenotypic expression known as acquired von Willebrand syndrome type 2A, which is frequently complicated by angiodysplasic gastrointestinal lesions that could bleed and lead to severe and difficult-to-treat anemia.

Aortic stenosis and anemia could determine a clinical burden potentially characterized by recurrent angina, syncope, and heart failure. These symptoms and signs are proportionally related to the severity of each of the two pathological conditions and their cumulative presence may act incrementally and confound diagnosis and treatment.

King et al. [8] reported 14 patients with Heyde's syndrome, all of whom had abrupt cessation of gastrointestinal bleeding post-SAVR, including 11 patients needing warfarin anticoagulation for their mechanical prosthesis; at follow-up, which ranged from 8 to 12 years, only 1 patient who underwent aortic valve replacement had recurrent bleeding secondary to excessive anticoagulation. Moreover, some case reports confirm the efficacy of SAVR on determining the remission of Heyde's syndrome's related anemia [7], [16], [17].This, to our knowledge, is the first case in the literature with a documented remission of the angiodysplasia-derived anemia after TAVI. The post-TAVI aortic regurgitation was moderate and remained stable during follow up. The post-procedural normalization of the Hb levels along with not particularly elevated aortic regurgitation velocity measurements (max 2.4 m/s), suggest relatively low levels of residual shear stress.We acknowledge the limitation that no evidence of improvement in the high molecular weight component of vWF is available, along with the fact that it is impossible to be absolutely certain if the improvement in gastrointestinal bleeding and anemia was related to the AVR, natural history, or to the other therapies given prior to surgery (e.g. endoscopic plasma coagulation), although the temporal relationship between TAVI and Hb and mean cell volume (MCV) levels suggests this hypothesis (Figure 3, Figure 4).

Figure 3.

Hemoglobin trend, treatment, and procedures. The patient was on chronic treatment with aspirin, and also treated with clopidogrel for one month after angioplasty with bare metal stent, and TAVI. The platelet count was stable, 250,000 ± 20,000/mm³. Hb, hemoglobin; TAVI, transcatheter aortic valve implantation.

Figure 4.

Mean cell volume trend. MCV, mean cell volume; TAVI, transcatheter aortic valve implantation.