Percutaneous transluminal aortic valve implantation for severe aortic valve stenosis in a patient with severe haemophilia A

Dear Sir, Herein we present a case report on what appears to be a previously unpublished topic: a 56-year-old man with severe haemophilia A and severe aortic valve stenosis who was successfully treated with percutaneous transluminal aortic valve implantation (TAVI). Haemophilia is a sex-linked recessive inherited disease that only affects males (females can carry the gene but are not affected). This disorder is caused by the deficiency of coagulation factor VIII (FVIII; haemophilia A) or FIX (haemophilia B) 1 and is classified as severe (FVIII <1 IU dL−1), moderate (2–5 IU dL−1) or mild (6–40 IU dL−1). While the life expectancy of a patient with haemophilia is increasing and now approaches that of the general male population, they are susceptible to age-related comorbidities such as cardiovascular disease 2. Therefore, it is necessary to manage cardiovascular events in elderly patients with haemophilia in a different manner to patients without haemophilia 3, 4. Aortic stenosis (SA) is the most common degenerative valve disease in Western countries and its incidence increases with age. The natural history of the disease is not altered by conservative treatment and at present, surgical aortic valve replacement is the gold standard treatment approach. However, ~30% of patients with severe symptomatic SA do not undergo surgical treatment because advanced age and comorbidities often coexist and mean that such patients are considered high-risk surgical patients. Until a few years ago the only alternative treatment was percutaneous valvuloplasty which, as recently highlighted by the prospective, randomized, multicentre PARTNER study 5, 6, provides a temporary improvement of clinical symptoms but does not change the prognosis of the disease. TAVI has rapidly become an important treatment option for patients who are not candidates for surgical valve replacement or who are considered high surgical risk 7. The effectiveness of TAVI has been demonstrated in the PARTNER study 5 which reported a 50% reduction in mortality at 1 year and a 55% reduction in the combined endpoint of mortality and rehospitalization in the TAVI group compared with standard therapy (medical and/or percutaneous valvuloplasty) in patients who were not surgical candidates. TAVI was non-inferior to traditional surgery for 1-year mortality among high-risk populations for whom surgery was still an option 6. Major bleeding events at 30 days occurred more frequently in the TAVI group than in the standard-therapy group (16.8% vs. 3.9%; P < 0.001)5, but were less frequent vs. traditional aortic valve replacement (9.3% vs. 19.5%; P < 0.001) 6. The rate of stroke was not significantly different between groups, either at 30 days or 1 year post-procedure 6. Over the long term, the PARTNER study showed that there was no significant difference in the rates of death, stroke and myocardial infarction between TAVI and aortic valve replacement 6. Of note, the complication rate is reduced with TAVI as operator experience increases, and TAVI has other advantages over aortic valve replacement, in that it does not require general anaesthesia, sternotomy or external cardiopulmonary bypass; the intervention time, perioperative and recovery times are also shorter with TAVI than aortic valve replacement. In 2008, the European Society of Cardiology and Cardiac Surgery published a consensus document which recommends the use of TAVI in patients with severe symptomatic SA who have a high surgical risk or a contraindication to surgery; TAVI is now considered an alternative surgery when the patient has a Society of Thoracic Surgeons score ≥8% or surgical risk associated with other procedures is prohibitive 8. The treatment of valvular disease using a transcatether technique, such as TAVI, is a valid and interesting alternative to conventional cardiac surgery. The elderly patient is therefore a principal candidate for percutaneous implantation, but only after the general condition of each patient is assessed, in conjunction with any comorbidities (which could affect life expectancy), together with the calculation of a ‘risk score’ resulting from surgery. Furthermore, accurate anatomical study must be performed to determine the type and size of prosthesis, as well as the ideal arterial route of access. Technical feasibility should be performed by echocardiography and multi-slice computerized tomography (CT), while coronary angiography, or coronary CT angiography, is employed to evaluate for possible concomitant coronary disease and the indication for coronary revascularization pre-valve implant. As mentioned above, published data show that TAVI can effectively treat elderly patients with high surgical risk or who are considered inoperable. In these patients it is possible to perform the procedure with a success rate of 95%, with no major difference between the implanted and native valves. Adding to the published data on the use of TAVI, we report a case of a 56-year-old man with severe haemophilia A, hepatitis C virus-related liver disease and severe aortic valve stenosis treated with percutaneous TAVI. In March 2011, this ex-smoker was admitted to hospital due to dyspnoea on moderate exertion (New York Heart Association-NYHA functional class II–III). He had a history of arterial hypertension, hyperthyroidism and a diagnosis of severe aortic valve stenosis, as well as a family history of ischaemic heart disease. An electrocardiogram (ECG) showed sinus rhythm, and a heart rate of 81 beats min−1. A two-dimensional echocardiogram demonstrated mild left atrial enlargement and concentric left ventricular (LV) hypertrophy with good LV function (ejection fraction 60%); aortic valve stenosis (peak gradient of 72 mmHg, mean gradient 41 mmHg and aortic valve area 0.6 cm2). Other echocardiogram observations included mild mitral regurgitation (MR 1+) due to fibro-calcification bi-leaflet, mild tricuspid regurgitation and systolic pulmonary arterial pressure (sPAP) of 49 mmHg; diameters of the other aortic segments were: aortic annulus 20 mm, sinuses of Valsalva 29 mm, sino-tubular junction 25 mm, ascending aorta 35 mm. An echo-colour Doppler excluded the presence of a stenosing plaque in the right and left iliac and femoral arteries. During the hospital stay, the patient underwent coronarography which showed coronary arteries without any haemodynamically significant lesions (Fig. 1a), but the dominant right coronary showed an irregularity deriving from the ascending aorta (Fig. 1b). Aortic valve replacement was indicated but due to his high bleeding risk and comorbidities, surgery was not considered feasible. The patient therefore received TAVI, which was performed in the cardiac catheterization laboratory under mild sedation and local anaesthesia with fluoroscopic guidance. The right femoral artery was surgically isolated (Fig. 2a) and cannulated with a sheath (18 Fr; William Cook Europe, Bjaeverskov, Denmark), and through a temporary pacemaker (Fig. 2b), rapid ventricular pacing at a frequency of 220 bpm was performed in order to provide transient decrease in cardiac output. When the desired frequency and stability were obtained, aortic valvuloplasty was performed using a Z MED balloon (B. Braun, Bethlehem, PA, USA) (22 × 50 mm; Fig. 2c and d). Based on echocardiographic and angiographic measurements, a self-expanding 29 mm Core Valve (Medtronic Inc., Minneapolis, MN, USA) device was advanced by Accutrak delivery system through the aortic arch and placed on the native valve (Fig. 2e). A control aortogram was performed and it showed minor non-significant periprosthetic regurgitation and stable positioning of the device on the aortic annulus (Fig. 2f). Echocardiogram analysis was repeated 24 h after the TAVI procedure to assess the function and positioning of the implant and to exclude other complications. An improvement was also observed in other parameters, notably a decrease in the sPAP to 35 mmHg. Overall, the outcome of the procedure was considered satisfactory. The plan for managing peripheral vascular complications was the use of specific closure systems, manual compression for 20–30 min or implantation of a self-expandable stent; however, the patient did not experience any adverse events during or after the procedure. ECG repeated 24 h after the TAVI procedure showed transient left bundle branch onset that resolved spontaneously. No atrio-ventricular block was detected via Holter ECG during routine monitoring 24 h before and up to 48 h after the procedure. During hospitalization, the patient was treated with a bolus injection of recombinant FVIII (rFVIII, Kogenate®, Bayer HealthCare LLC, Whippany, NJ, USA) 80 IU kg−1 prior to surgery and then at a dose of 30 IU kg−1 every 12 h following surgery, reaching factor levels of 50% and 30% with those dosages. During the procedure, the patient received a bolus dose of heparin 5000 IU. The patient received continued prophylactic therapy with rFVIII infusion (25 IU kg−1) every 12 h for 15 days and low molecular weight heparin 100 IU kg−1 day−1. After 6 days of hospital stay, we discharged the patient in NYHA class I–II on medical therapy without any complications. The patient's health was monitored through periodic visits to the cardiac unit and with echocardiogram examination. Following hospital discharge no adverse cardiac events were reported, nor were any further interventions or re-hospitalization required. A year after the TAVI procedure, the patient had maintained a satisfactory response in terms of cardiac outcomes and symptoms. The patient did not report any thrombotic or haemorrhagic adverse events and there were no complications noted during long-term follow-up of almost 2 years (as of March 2015). Transluminal aortic valve implantation has rapidly become an important treatment option for patients who are not candidates for surgical valve replacement or with high surgical risk and on the basis of our patient, it appears to be a feasible, safe and effective treatment in patients with aortic valve stenosis and haemophilia. However, the full utility of this intervention can only be confirmed with data from large prospective studies. All the authors were involved in the clinical assistance of the patient and in the analysis and interpretation of the data. All the authors drafted, critically revised and approved the final version of the manuscript before submission. Matt Weitz of Springer Healthcare Communications provided medical writing assistance (English editing and manuscript formatting) in the preparation of this article. This assistance was funded by Bayer Healthcare. The authors stated that they had no interests which might be perceived as posing a conflict or bias.