Description of the condition
Acquired aortic valve (AV) stenosis is the degenerative disease of the AV in adults. In Europe, 2% to 7% of the population older than 65 years suffers from severe disease, and it is the most frequent heart valve disease (Iung 2003; Nkomo 2006). Other more rare aetiologies are rheumatic and congenital AV stenosis.
The disease has a chronic course, usually over decades, with gradual lipid accumulation, inflammation, calcification and sclerosis of the valve, and obstruction of the left ventricular outflow (Freeman 2005; Carabello 2009). The cardiac intracavitary pressure overload leads to adaptive concentric left ventricular hypertrophy keeping the wall stress within normal ranges and preserving the chamber volume and ejection fraction (Spann 1980). The hypertrophic left ventricle will eventually become insufficient to overcome the high systolic pressure and/or be in a depressed contractile state and this leads to decreasing ejection fraction (Krayenbuehl 1988). Concomitant coronary artery disease (CAD) will exacerbate this myocardial dysfunction (Marcus 1982).
The natural history of the disease consists of a prolonged latent asymptomatic period which varies widely between individuals (Ross 1968; Otto 1997; Rosenhek 2000; Pellikka 2005). In adults over 65 years of age, about 26% have sclerosis and thickening of the AV without obstruction of the left ventricle (Stewart 1997; Otto 1999). Among those without CAD, 10% will have died from cardiovascular causes after five years compared to 6% of adults with a normal AV (adjusted relative risk 1.66 (95% confidence interval, 1.23 to 2.23)) (Stewart 1997; Otto 1999). About 2% to 7% of adults over 65 years of age have symptomatic and haemodynamic significant severe AV stenosis (Iung 2003; Nkomo 2006). Often symptoms of dyspnoea on exertion, angina and syncope will develop, and the prognosis changes dramatically with an average survival of two to three years with a risk of sudden death (Ross 1968; Turina 1987; Horstkotte 1988; Iivanainen 1997; Rosenhek 2010; Clark 2012).
Most asymptomatic patients are closely monitored for disease progression and development of symptoms and usually not considered for corrective surgery. In symptomatic patients with severe AV stenosis (defined echocardiographically as effective opening valve area less than 1 cm2 (indexed effective opening valve area less than 0.6 cm2/m2 body surface area), mean valve gradient greater than 40 mm Hg or jet velocity greater than 4.0 m/s) and no prohibitive co-morbidities, surgical aortic valve replacement (SAVR) is usually considered indicated. Concomitant coronary artery bypass grafting (CABG) is also indicated if concurrent significant CAD exist (Bonow 2008; Vahanien 2012).
AV stenosis is associated with some of the same genetic and clinical factors contributing to atherosclerosis in CAD such as increased age, male sex, smoking, hypertension, diabetes mellitus, and raised serum low-density lipoprotein (Stewart 1997; Thanassoulis 2013).
Description of the intervention
Since the AV stenosis disease process is similar to CAD (Carabello 2009), statins have been suggested but failed to slow the progression of the disease in randomised clinical trials (Rossebø 2008; Chan 2010). Patients with evidence of decompensated congestive heart failure can cautiously be treated with digitalis, diuretics and angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, but the outcome will not improve compared to the natural history (Vahanien 2012). Associated hypertension and atrial fibrillation should be managed cautiously in the usual fashion, and cardiac risk factors should be modified. No other disease modifying agents have been identified (Bonow 2008; Vahanien 2012).
In retrospective observational studies, SAVR has been shown to improve symptoms, quality of life, and left ventricular ejection fraction compared to the preoperative status (Murphy 1981; Lund 1990; Khan 1998; Vahanien 2012). In a small observational study comparing patients receiving SAVR to patients not receiving SAVR, both the one year survival (90% compared to 65%) and the three-year survival (87% compared to 21%) were significantly higher in the SAVR group (Schwarz 1982). After SAVR, mid-term and long-term survival may be close to the age-matched general population in older low-risk patients, e.g., 80 years and older, with survival rates of 84% to 93%, 56% to 77% and 38% to 56% at one, five and ten years, respectively (Leontyev 2009; ElBardissi 2011; Mølstad 2012). However, in younger patients and in moderate-risk and high-risk older patients lower survival rates compared to age-matched controls may be expected (Leontyev 2009; Vahanien 2012).
SAVR involves sternotomy, cardio-pulmonary bypass, aortic cross-clamping, and cardioplegic arrest before the diseased valve can be excised and a valve prosthesis can be sutured in place. The procedure carries a low operative risk in younger patients without any significant co-morbidities (30-day mortality 1% to 4% in patients younger than 70 years) (Brown 2009). The risk increases substantially with increasing age, reduced left ventricular function, concomitant CAD, frailty and other co-morbidities (30-day mortality 4% to 8% in selected older patients) (Pereira 2002; Florath 2003; Florath 2010; Thourani 2011; Vahanien 2012).
Different operative risk calculators in cardiac surgery including the Society of Thoracic Surgery Predicted Risk of Mortality (STS-PROM) score and the European System for Cardiac Operative Risk Evaluation (EuroSCORE I and II) have been developed to identify the high-risk surgical patient (Nashef 1999; O'Brien 2009; Nashef 2012), but these are inadequate and generally overestimate the operative mortality in SAVR (Wendt 2009). Almost one-third of patients referred for valve intervention will not receive valve replacement because of presumable prohibitive high surgical risk, and a less invasive treatment option would be attractive (Iung 2005; Bach 2009).
At the end of the 1980s, AV balloon valvuloplasty was developed for inoperable patients. The treatment resulted in mid-term improvements in quality in life, but the recurrence of stenosis in most patients after 6-12 months and the lack of survival benefit rapidly terminated its use (Tissot 2011). In 1989, the first animal experiments with a biological, balloon-expandable valve prosthesis mounted in a catheter were carried out in pigs, and in 2000 the first stented valve prosthesis was implanted in a human with a diseased pulmonary valve (Cribier 2012).
Transcatheter aortic valve implantation (TAVI) was originally developed in 1992 in a porcine model (Andersen 1992), and clinically introduced in 2002 as a minimally-invasive treatment for patients who are considered ineligible for valve surgery (Cribier 2002). The term TAVI comprises different valve prosthesis types, deployment systems, and approaches to the stenosed valve. Originally developed as a transvenous transseptal technique, the procedure is currently performed on the beating heart either antegrade transapically through a small left anterior thoracotomy or retrograde through the arterial system using either the femoral, subclavian, or carotid artery, or with the direct transaortic approach. The artery can be surgically exposed or punctured. Before prosthesis deployment a standard AV balloon valvuloplasty is typically performed (Walther 2011; Webb 2011).
Currently, there are a number of European Conformity marked TAVI prostheses and deployment systems available for commercial use in Europe, and more are being developed. The two most widely-used systems are the Edwards SAPIEN system with a balloon-expandable bioprosthesis (Edwards Lifescience Inc., Irvine, CA, USA), which has also been FDA approved for inoperable patients in the United States, and the CoreValve System with a self-expandable bioprosthesis (Medtronic Inc., Minneapolis, MN, USA) (Cribier 2012).
Postoperative complications related to SAVR stem from the surgical trauma with sternotomy, cardio-pulmonary bypass, aortic cross clamping, and cardioplegic cardiac arrest. In TAVI many of the SAVR complications are potentially avoided but others are potentially exacerbated such as neurological and vascular lesions (Kahlert 2010; Rodés-Cabau 2011; Stortecky 2012). Retrograde catheter passage in the aortic arch and ascending aorta can generate atherosclerotic emboli. At the same time, TAVI specific complications have been encountered including conduction abnormalities (typically atrio-ventricular and bundle branch block), prosthesis misplacement, incomplete frame expansion leading to valvular and paravalvular leakage, prosthesis embolisation, aortic and ventricular perforations, and arterial access lesions (Nuis 2011a).
Since operator experience has grown, pre-procedure measurements of the aortic root and native valve size have become more precise, imaging techniques and implantation systems have improved and decreased in size, many of the above complications have become more rare (Nuis 2011b).
National and international registries have documented good short and mid-term safety results after TAVI in patients considered at prohibitive high risk for surgery with a 95% to 100% procedure success rate, and a 30-day mortality, stroke and myocardial infarction rate at 5% to 12%, 2% to 10%, and 1% to 4%, respectively. These figures are combined with sustained prosthesis function, clinical and quality of life improvements, and survival rates of 76% to 79% after one year and 71% to 74% after two years (Piazza 2008; Moat 2011; Zahn 2011; Gilard 2012; Jilaihawi 2012; Krane 2012). However, about 25% of patients treated with the CoreValve System and 10% of patients treated with the Edwards Sapien system will require a permanent pacemaker (Khawaja 2011; Gilard 2012). Long-term durability results beyond five years are lacking, and it is unclear how the prevalent paravalvular leakage will affect symptoms, cardiac structure and function (Ye 2010; Buellesfeld 2011; Moat 2011; Litzler 2012; Rodés-Cabau 2012; Toggweiler 2012; Ussia 2012).
The effect of the specific valve bioprosthesis and deployment system used, mode of implantation (transarterial versus transapical), and concomitant CAD are not known in detail (Dewey 2010; Moat 2011).
How the intervention might work
The TAVI intervention is designed to treat degenerative AV stenosis. The diseased stenosed valve is first dilated by a balloon-valvuloplasty and, to avoid re-stenosis and valve insufficiency, a valve prosthesis is implanted. The intervention is minimally invasive since it can be done on the beating heart using a catheter either through a small thoracotomy or through an arterial puncture. By avoiding sternotomy, cardio-pulmonary bypass, and aortic cross-clamping the intervention might lower complication and morbidity rates, without compromising the favourable functional and prognostic results as seen in the current standard treatment (SAVR) (Vahanian 2008).
Why it is important to do this review
Degenerative AV stenosis is the most prevalent heart valve disease. TAVI is a new attractive treatment modality with an extremely rapid dissemination in clinical use. Originally developed for inoperable patients, the technique is now used in patients with lower operative risk profiles based primarily on data from national and international registries (Vahanian 2008; Leon 2011; Kappetein 2013). The severity of AV stenosis per se for which intervention is considered has apparently not changed yet (Vahanien 2012). Clear evidence from randomised data and not observational studies is essential to guide patients and clinicians in finding the most effective and safe intervention for different subsets of patients with severe AV stenosis (Vahanian 2008; Higgins 2011; Leon 2011; Kappetein 2013).