Transcatheter aortic valve implantation: current status and future perspectives

Transcatheter aortic valve implantation: current status and future perspectives Abstract In the 16 years since the first pioneering procedure, transcatheter aortic valve implantation (TAVI) has come of age and become a routine strategy for aortic valve replacement, increasingly performed under conscious sedation via transfemoral access. Simplification of the procedure, accumulation of clinical experience, and improvements in valve design and delivery systems have led to a dramatic reduction in complication rates. These advances have allowed transition to lower risk populations, and outcome data from the PARTNER 2A and SURTAVI trials have established a clear evidence base for use in intermediate risk patients. Ongoing studies with an expanding portfolio of devices seem destined to expand indications for TAVI towards lower risk, younger and asymptomatic populations. In this article, we outline recent advances, new devices and current guidelines informing the use of TAVI, and describe remaining uncertainties that need to be addressed. Aortic stenosis, Aortic valve replacement, Computed tomography, Transcatheter aortic valve implantation, Transcatheter aortic valve replacement, TAVI, TAVR Introduction Since the first procedure in 2002, transcatheter aortic valve implantation (TAVI) has revolutionized the management of aortic stenosis (AS)1 and become the standard of care for patients with AS at prohibitive surgical risk, and the preferred treatment for many intermediate and high risk elderly patients.2 Its clinical and market impact cannot be overstated; over 300 000 patients have now received a transcatheter aortic valve in a global market worth $2 billion per annum. Newer generations of transcatheter valve design and optimization of patient selection, procedural planning and technique have driven stepwise improvements in efficacy and reduction in complication rates. The breakaway success of TAVI has been underpinned by the combination of patients in need and collaboration between cardiologists, surgeons, clinical investigators, and the device industry. While surgical aortic valve replacement (SAVR), first performed in 1960, is an established and durable option for AS, up to a third of patients are deemed unsuitable due to excess procedural risk.3 A lack of alternative therapeutic options led to the conception, development, and clinical application of the balloon-expandable Cribier-Edwards transcatheter valve. The pioneering success of the first procedure has since been translated into routine clinical practice through a series of landmark clinical trials enrolling over 15 000 patients [including eight randomized controlled trials (RCTs)] since 2007. As TAVI comes of age, there are new frontiers and potential hurdles. Percutaneous treatment is challenging SAVR in lower risk patient cohorts, and ongoing trials in patients with asymptomatic AS and moderate AS with heart failure may overturn traditional indications for valve replacement. However, questions remain over long-term valve durability, stroke risk, and complications such as haemorrhage, conduction abnormalities, paravalvular leak (PVL), and infective endocarditis. In this context, we review the state-of-the-art in TAVI, providing a current perspective on recent and ongoing trials, the contemporary device portfolio, clinical guidelines and strategies to further reduce complication rates. Current perspectives on transcatheter aortic valve implantation A decade of clinical experience with TAVI has led to substantial simplification of the procedure. Improved valve and delivery catheter technologies have been transformative. Newer generation devices offer improved sizing, deliverability and positioning compared with earlier forerunners, and valve implantation via transfemoral access is now achievable in approximately 90% of patients using expandable sheaths and/or atraumatic, small-bore delivery catheters. Pre-procedural planning and valve selection have been advanced by standardized computed tomography (CT) imaging, which has emerged as the optimal modality for assessing vascular access, annular dimensions and valve morphology, and predicting potential complications. An increasing proportion of TAVI cases worldwide are now performed using a ‘minimalist’ approach, under conscious sedation (CS), local anaesthesia, and transthoracic echocardiographic guidance.4 Conscious sedation is used routinely for transfemoral TAVI across much of Europe and has the potential advantages of reduced procedural time, faster recovery and reduced cost, but is associated with reduced use of peri-procedural transoesophageal echocardiography (TOE). While valve deployment and assessment of residual aortic regurgitation can be guided by fluoroscopy, aortography, haemodynamic measurement and standby transthoracic imaging, lack of TOE guidance is associated with increased contrast use and greater risk of post-procedural aortic regurgitation.4,5 This must be weighed against emerging US propensity-matched data from almost 11 000 patients undergoing transfemoral TAVI, which demonstrate that CS is associated with a shorter hospital stay and reduced short-term mortality.6 Above all, the chosen approach should be tailored for individual patients: for example, a limited post-procedural TOE to exclude PVL may assist in those with chronic kidney disease where contrast use is limited. Intracardiac echocardiography is also a valuable tool in specific high-risk patients where continuous echocardiographic guidance is desirable.7 This evolution of TAVI has led to a reduction in procedural mortality and major complication rates. Data from the UK TAVI registry (Figure 1) demonstrate a large reduction in mortality prior to hospital discharge (9.09% in 2008, 1.84% in 20168), and progressive reductions in mortality and complication rates have also been observed in registry studies from France, Germany, Japan and the USA.10–13 Between 2008 and 2016 the incidence of stroke fell from 3.4% to 2.2%, requirement for haemofiltration from 6.4% to 0.9%, and tamponade from 5.3% to 1.4%. These improvements have been associated with reduced length of stay, with median time from procedure to discharge falling from 130 h (2013) to 64 h (2016). This is likely to fall further with structured early discharge programmes. For example, preliminary outcomes from the Vancouver 3M Clinical Pathway show safe one-day discharge in up to 80% of patients after transfemoral TAVI, achieved by a minimalist procedure, avoidance of routine intensive care and use of criteria-led discharge.14 In a US cohort of 360 patients undergoing uncomplicated transfemoral TAVI with a Sapien valve, male sex, absence of atrial fibrillation (AF), lower creatinine, and young age were factors associated with safe next day discharge.15 Figure 1 View largeDownload slide Temporal change in complication rates in patients undergoing transcatheter aortic valve implantation. Over time, there has been a major reduction in the incidence of in-hospital mortality (A), serious complications including tamponade (B), post-procedural dialysis (C), and stroke prior to discharge (D). Data from British Cardiovascular Intervention Society TAVI Audit.8,9 Figure 1 View largeDownload slide Temporal change in complication rates in patients undergoing transcatheter aortic valve implantation. Over time, there has been a major reduction in the incidence of in-hospital mortality (A), serious complications including tamponade (B), post-procedural dialysis (C), and stroke prior to discharge (D). Data from British Cardiovascular Intervention Society TAVI Audit.8,9 Despite these improvements, global use of TAVI is patchy with several barriers to wider geographical use. First, device cost is currently prohibitive (>$30 000 in the USA) and international uptake correlates strongly with healthcare spend.16 Device costs have risen over time and seem unlikely to stabilize until, there are more competing valves available on the market. Second, infrastructural development in countries where there is no existing Heart Valve Centre model stretches scarce capital resources. Third, in populations with specific anatomic challenges (for example smaller ilio-femoral vessels, as in China and Asia) further valve innovation and specific studies are required to demonstrate equivalent outcomes to those seen in European and US trials. Nevertheless, the potential scope for future TAVI growth is well illustrated in Germany, where the number of patients undergoing TAVI exceeded SAVR by 2014 (while surgical numbers remained stable).17 Transcatheter aortic valve implantation for intermediate and low risk patients Two landmark RCTs have recently reported outcomes of TAVI in comparison with SAVR in elderly patients with severe symptomatic AS at intermediate surgical risk (Table 1).18,19 PARTNER 2A randomized 2032 patients with a Society of Thoracic Surgeons (STS) predicted mortality risk of 4–10% to TAVI with the Sapien XT valve, or SAVR.18 The mean age was 82 years with a mean STS score of 5.8%, well below that of the high risk PARTNER I and CoreValve US Pivotal trials (where mean STS scores were 12% and 7.4%, respectively).20,21 At 2 years, PARTNER 2A found no significant difference in the primary endpoint, a composite of death from any cause or disabling stroke. Furthermore, the transfemoral TAVI subset had a significantly lower rate of death or disabling stroke than those undergoing SAVR, a finding confirmed in a subsequent meta-analysis of the PARTNER 1A, US CoreVALVE, NOTION, and PARTNER 2A trials.22 Table 1 Randomized trials of TAVI vs. SAVR in intermediate risk patients with severe symptomatic AS Study  Design  Size  Predicted STS (%)  Age/STS  Trial arms  Outcomes  Complication profile  PARTNER 2A  RCT  2032  4–10  Mean age 82 years Mean STS 5.8%  TAVI (Sapien XT) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 19.3% TAVI vs. 21.1% SAVR, HR for TAVI 0.89, 95% CI 0.73–1.09; P = 0.25  TAVI: higher rate of major vascular complications (7.9% vs 5.0%); lower rates of life-threatening bleeding (10.4% vs 43.4%) and new atrial fibrillation (9.1% vs 26.4%) (all p<0.01)  SURTAVI  RCT  1077  3–15  Mean age 79.8 years Mean STS 4.5%  TAVI (CoreValve/Evolut R) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 12.6% TAVI vs. 14.0% SAVR, 95% credible interval −5.2 to 2.3%; P > 0.999  TAVI: higher rate of major vascular complications (6.0 vs. 1.1%), residual moderate or severe paravalvular leak (5.3% vs. 0.6%), and pacemaker implantation (25.9% vs. 6.6%); lower rates of acute kidney injury (1.7% vs. 4.4%) (differences outside 95% credible interval)  Study  Design  Size  Predicted STS (%)  Age/STS  Trial arms  Outcomes  Complication profile  PARTNER 2A  RCT  2032  4–10  Mean age 82 years Mean STS 5.8%  TAVI (Sapien XT) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 19.3% TAVI vs. 21.1% SAVR, HR for TAVI 0.89, 95% CI 0.73–1.09; P = 0.25  TAVI: higher rate of major vascular complications (7.9% vs 5.0%); lower rates of life-threatening bleeding (10.4% vs 43.4%) and new atrial fibrillation (9.1% vs 26.4%) (all p<0.01)  SURTAVI  RCT  1077  3–15  Mean age 79.8 years Mean STS 4.5%  TAVI (CoreValve/Evolut R) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 12.6% TAVI vs. 14.0% SAVR, 95% credible interval −5.2 to 2.3%; P > 0.999  TAVI: higher rate of major vascular complications (6.0 vs. 1.1%), residual moderate or severe paravalvular leak (5.3% vs. 0.6%), and pacemaker implantation (25.9% vs. 6.6%); lower rates of acute kidney injury (1.7% vs. 4.4%) (differences outside 95% credible interval)  Table 1 Randomized trials of TAVI vs. SAVR in intermediate risk patients with severe symptomatic AS Study  Design  Size  Predicted STS (%)  Age/STS  Trial arms  Outcomes  Complication profile  PARTNER 2A  RCT  2032  4–10  Mean age 82 years Mean STS 5.8%  TAVI (Sapien XT) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 19.3% TAVI vs. 21.1% SAVR, HR for TAVI 0.89, 95% CI 0.73–1.09; P = 0.25  TAVI: higher rate of major vascular complications (7.9% vs 5.0%); lower rates of life-threatening bleeding (10.4% vs 43.4%) and new atrial fibrillation (9.1% vs 26.4%) (all p<0.01)  SURTAVI  RCT  1077  3–15  Mean age 79.8 years Mean STS 4.5%  TAVI (CoreValve/Evolut R) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 12.6% TAVI vs. 14.0% SAVR, 95% credible interval −5.2 to 2.3%; P > 0.999  TAVI: higher rate of major vascular complications (6.0 vs. 1.1%), residual moderate or severe paravalvular leak (5.3% vs. 0.6%), and pacemaker implantation (25.9% vs. 6.6%); lower rates of acute kidney injury (1.7% vs. 4.4%) (differences outside 95% credible interval)  Study  Design  Size  Predicted STS (%)  Age/STS  Trial arms  Outcomes  Complication profile  PARTNER 2A  RCT  2032  4–10  Mean age 82 years Mean STS 5.8%  TAVI (Sapien XT) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 19.3% TAVI vs. 21.1% SAVR, HR for TAVI 0.89, 95% CI 0.73–1.09; P = 0.25  TAVI: higher rate of major vascular complications (7.9% vs 5.0%); lower rates of life-threatening bleeding (10.4% vs 43.4%) and new atrial fibrillation (9.1% vs 26.4%) (all p<0.01)  SURTAVI  RCT  1077  3–15  Mean age 79.8 years Mean STS 4.5%  TAVI (CoreValve/Evolut R) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 12.6% TAVI vs. 14.0% SAVR, 95% credible interval −5.2 to 2.3%; P > 0.999  TAVI: higher rate of major vascular complications (6.0 vs. 1.1%), residual moderate or severe paravalvular leak (5.3% vs. 0.6%), and pacemaker implantation (25.9% vs. 6.6%); lower rates of acute kidney injury (1.7% vs. 4.4%) (differences outside 95% credible interval)  SURTAVI enrolled 1746 intermediate risk patients (estimated surgical mortality 3–15%) at 87 centres in Europe, the USA and Canada.19 Patients were randomized to TAVI using the CoreValve system (CoreValve 84%, next generation Evolut R 16%) or SAVR. The mean age was 79.8 years with a mean STS score of 4.5%. As in PARTNER 2A, SURTAVI found no significant difference in the primary endpoint (composite of death from any cause or disabling stroke) between TAVI and SAVR at 2 years. Further support for TAVI in intermediate risk patients has come from observational data in the SAPIEN 3 registry.23 In this cohort of 1077 intermediate risk patients (mean age 82 years, STS score 5.3%), TAVI was superior to a propensity-matched SAVR cohort, with a lower incidence of the composite of all-cause mortality, stroke and moderate or severe aortic regurgitation [pooled weighted proportion difference −9.2%, 95% confidence interval (CI) −13 to −5.4; P < 0.0001]. While PARTNER2A and SURTAVI found no difference in the headline primary outcome, there were important differences in the complication profiles of TAVI and SAVR. In PARTNER 2A, at 30 days TAVI was associated with a higher rate of major vascular complications (7.9% vs. 5.0%), but lower rates of new AF (9.1% vs. 26.4%) and life-threatening bleeding (10.4% vs. 43.4%) (all P < 0.01). In the trial, this included fatal bleeding, bleeding into a critical organ, bleeding causing hypovolaemic shock, or severe hypotension (requiring vasopressors or surgery), an overt source of bleeding with a drop in haemoglobin of ≥5 g/dL, or a transfusion of ≥4 units of blood or packed red cells. In SURTAVI, TAVI was also associated with higher rates of major vascular complication (6.0 vs. 1.1%), as well as residual moderate or severe PVL (5.3% vs. 0.6%), and pacemaker implantation (25.9% vs. 6.6%), but lower rates of acute kidney injury (1.7% vs. 4.4%) (differences outside 95% credible interval). The next frontier is patients at low surgical risk (STS < 4%), who account for 80% of patients undergoing SAVR. There are already early data in this group from the NOTION study, a small all-comers trial of 280 patients randomized to the CoreValve or SAVR.24 80% of patients had a mean STS score <4%, with a mean STS score in the TAVI arm of 2.9%. No difference was identified in the primary composite endpoint [all-cause mortality, stroke, or myocardial infarction (MI)] at 1 year (13.1% TAVI vs. 16.3% SAVR, −3.2% absolute difference, P = 0.43), although the study may have been underpowered. Transcatheter aortic valve implantation in low risk populations is being definitively addressed in three ongoing RCTs: PARTNER 3 (NCT02675114), Medtronic Evolut Low Risk (LR) (NCT02701283), and NOTION-2 (NCT02825134) (Figure 2). Notably, NOTION-2 is only enrolling patients <75 years and is therefore likely to report outcomes in the youngest TAVI population so far. Figure 2 View largeDownload slide Key ongoing randomized clinical trials in transcatheter aortic valve implantation (blue, Edwards Sapien 3; red, Medtronic Evolut R; green, any transcatheter valve), which will (A) expand the evidence base to patients with severe aortic stenosis at low surgical risk, (B) evaluate transcatheter aortic valve implantation for expanded indications, (C) define the optimal peri-procedural antithrombotic regime, and (D) clarify the role of cerebral protection devices. See text for specific details—timescales shown are estimated dates to primary endpoint completion (as shown on clinicaltrials.gov). Figure 2 View largeDownload slide Key ongoing randomized clinical trials in transcatheter aortic valve implantation (blue, Edwards Sapien 3; red, Medtronic Evolut R; green, any transcatheter valve), which will (A) expand the evidence base to patients with severe aortic stenosis at low surgical risk, (B) evaluate transcatheter aortic valve implantation for expanded indications, (C) define the optimal peri-procedural antithrombotic regime, and (D) clarify the role of cerebral protection devices. See text for specific details—timescales shown are estimated dates to primary endpoint completion (as shown on clinicaltrials.gov). Expanding indications for transcatheter aortic valve implantation As the incidence of complications associated with TAVI falls below that of SAVR, a debate is opening as to whether the classical indications for aortic valve replacement still stand. Transcatheter aortic valve implantation potentially provides an opportunity to intervene safely earlier in the natural history of AS using a minimally invasive technique that is highly acceptable to patients. However, given that long-term valve durability remains to be established, and redo valve procedures and coronary interventions following TAVI may be more challenging, its expanded use in younger populations must be supported by high quality clinical evidence. Trials are ongoing in two specific groups: those with moderate AS and impaired ventricular function, and asymptomatic patients with severe AS. Moderate aortic stenosis with impaired ventricular function Impaired left ventricular function is reported in up to a third of patients over 85 years of age, and commonly co-exists with AS.25 Outcomes in heart failure are improved by reduction in afterload, which improves cardiac output and organ perfusion. Aortic valve replacement reduces afterload in patients with severe aortic valve disease and left ventricular impairment to improve symptoms, contractile function, and survival.26 Patients with moderate AS and left ventricular dysfunction are at high risk of adverse outcome, with heart failure hospitalization or death occurring in 48% of patients at 4 years of follow-up in a recent series.27 It is unknown, however, whether valve replacement in patients with impaired ventricular function and co-existent moderate AS improves outcome. The ongoing TAVR UNLOAD trial (NCT02661451; Figure 2) will address precisely this question in patients with symptomatic heart failure, impaired left ventricular function (ejection fraction <50%, but >20%), and moderate AS [mean gradient (MG) ≥20 mmHg and <40 mmHg, and aortic valve area (AVA) 1.0–1.5 cm2 at rest]28 who will be randomized to transfemoral TAVI using the Sapien 3 valve or optimal heart failure therapy only. The primary endpoint is the hierarchical occurrence of all-cause death, disabling stroke, hospitalization for heart failure, symptomatic aortic valve disease, non-disabling stroke, and change in quality of life measures at 1 year. Asymptomatic severe aortic stenosis In asymptomatic AS, the upfront risks of SAVR have conventionally been thought to outweigh the benefits of intervention, leading to a strategy of active surveillance until symptoms or left ventricular impairment emerge.29 This approach has several problems. It is not always straightforward to determine whether symptoms are present, or whether AS is definitively responsible. The rate of progression of AS is variable, and despite surveillance ∼1% of asymptomatic patients die suddenly each year.30,31 In others, fibrosis or irreversible decline in cardiac function develop by the time of SAVR, leading to increased procedural risk and ongoing left ventricular dysfunction. While exercise treadmill testing or stress echocardiography can assist with risk stratification, even in those with a negative stress test (‘truly asymptomatic’), there is variable progression and an ongoing risk of sudden death.32,33 The development of TAVI as a less invasive lower risk procedure for aortic valve replacement may alter the risk-benefit balance of early intervention for patients with asymptomatic severe AS—a hypothesis currently being tested in the Early TAVR trial (NCT03042104; Figure 2). This study will randomize 1109 asymptomatic patients ≥65 years with severe AS (peak velocity ≥4m/s or MG ≥40 mmHg, AVA ≤1.0cm2 or AVA index ≤0.6) and a negative treadmill stress test to TAVI with the Edwards Sapien 3 valve or routine clinical surveillance. Primary endpoint data (composite of all-cause death, all stroke, and unplanned cardiovascular hospitalization) should be complete in December 2021. In parallel, there are evolving approaches to identify specific higher risk patient subsets who will benefit from early valve replacement. The ongoing EvoLVeD trial (NCT03094143) is currently assessing the significance of mid-wall fibrosis on cardiac magnetic resonance imaging (MRI)—patients with asymptomatic severe AS and mid-wall fibrosis are being randomized to valve replacement (by TAVI or SAVR) or routine care, with a primary endpoint of all-cause mortality or unplanned AS-related hospitalization. Current and future devices Clinical experience with TAVI is dominated by the Edwards Sapien and Medtronic CoreValve systems, but several newer valves are competing in expanding markets on design, repositionability and retrievability, and price. Improved valve sizing and design, and smaller delivery catheters have significantly reduced PVL and post-procedural complications, and this trend is likely to continue with future iterations.34 A comparison between the main valve systems is shown in Table 2. Many valves now incorporate sealing systems to reduce paravalvular aortic regurgitation—exemplified by an outer skirt on the Sapien 3 and a pericardial wrap on the Evolut PRO. The Acurate valve (Boston Scientific, previously Symetis) is a self-expanding supra-annular valve with a low rate of permanent pacemaker (PPM) implantation.35 The Portico valve (Abbott) is a self-expanding, fully resheathable and retrievable valve with leaflet geometry designed to function in both round and elliptical configurations. The repositionable and retrievable Lotus Valve is deployed using controlled mechanical expansion but has been recalled worldwide due to problems with its release mechanism.36 The JenaValve (JenaValve Technology, Germany) and J-valve (JieCheng Medical, China) have active fixation mechanisms that anchor the prosthesis to the valve leaflets, providing stability in the context of aortic regurgitation. The JenaValve is currently the only transcatheter valve with a Conformité Européene (CE) mark for use in patients with aortic regurgitation. Two further valves from China, the Venus-A® valve (Venus Medtech) and VitaFlow® (Microport), are at an advanced stage of development with high rates of procedural success in the challenging cohort of patients with bicuspid aortic valve (BAV) disease.37 Table 2 Comparative overview of selected transcatheter aortic valve systems   Acurate (Boston Scientific)  Allegra (NVT)  Centera (Edwards)  Evolut PRO (Medtronic)  Evolut R (Medtronic)  JenaValve (JenaValve)  Portico (St Jude)  Sapien 3 (Edwards)  VenusA (Venus Medtech)                      Design (leaflets, frame and delivery)  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Cobalt-chromium Balloon-expandble  Porcine pericardium Nitinol Self-expanding  Delivery routes and sheath size  TF, TA, TS 18 Fr/19 Fr  TF 18 Fr  TF, TS 14 Fr  TF, TAo, TS 16 Fr  TF, TAo, TS 14 Fr  TF, TA 18 Fr  TF, TA 18 Fr/19 Fr  TF, TA, TAo 14 Fr/16 Fr  TF, TA, TS 18 Fr/20 Fr  CE mark (years)  2011  2017  Awaited  2017  2013  2011 (AS) 2013 (AR)  2012  2014  NA  Specific advantages  Low PPM requirement  Resheathable up to 70% of deployment  Resheathable up to 85% deployment. PTFE skirt to reduce PVL. Motorized delivery system  Resheathable up to 80% deployment Double layer porcine pericardial skirt  Resheathable up to 80% deployment. Upcoming RCT data in low risk population  Active fixation for use in AR  Resheathable up to 85% deployment  External skirt to reduce PVL. Upcoming RCT data in low risk population  Experience in bicuspid valve population in China; reduced cost    Acurate (Boston Scientific)  Allegra (NVT)  Centera (Edwards)  Evolut PRO (Medtronic)  Evolut R (Medtronic)  JenaValve (JenaValve)  Portico (St Jude)  Sapien 3 (Edwards)  VenusA (Venus Medtech)                      Design (leaflets, frame and delivery)  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Cobalt-chromium Balloon-expandble  Porcine pericardium Nitinol Self-expanding  Delivery routes and sheath size  TF, TA, TS 18 Fr/19 Fr  TF 18 Fr  TF, TS 14 Fr  TF, TAo, TS 16 Fr  TF, TAo, TS 14 Fr  TF, TA 18 Fr  TF, TA 18 Fr/19 Fr  TF, TA, TAo 14 Fr/16 Fr  TF, TA, TS 18 Fr/20 Fr  CE mark (years)  2011  2017  Awaited  2017  2013  2011 (AS) 2013 (AR)  2012  2014  NA  Specific advantages  Low PPM requirement  Resheathable up to 70% of deployment  Resheathable up to 85% deployment. PTFE skirt to reduce PVL. Motorized delivery system  Resheathable up to 80% deployment Double layer porcine pericardial skirt  Resheathable up to 80% deployment. Upcoming RCT data in low risk population  Active fixation for use in AR  Resheathable up to 85% deployment  External skirt to reduce PVL. Upcoming RCT data in low risk population  Experience in bicuspid valve population in China; reduced cost  AR, aortic regurgitation; AS, aortic stenosis; PPM, permanent pacemaker; PVL, paravalvular leak; TA, transapical; TAo, transaortic; TF, transfemoral; TS, trans-subclavian. Table 2 Comparative overview of selected transcatheter aortic valve systems   Acurate (Boston Scientific)  Allegra (NVT)  Centera (Edwards)  Evolut PRO (Medtronic)  Evolut R (Medtronic)  JenaValve (JenaValve)  Portico (St Jude)  Sapien 3 (Edwards)  VenusA (Venus Medtech)                      Design (leaflets, frame and delivery)  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Cobalt-chromium Balloon-expandble  Porcine pericardium Nitinol Self-expanding  Delivery routes and sheath size  TF, TA, TS 18 Fr/19 Fr  TF 18 Fr  TF, TS 14 Fr  TF, TAo, TS 16 Fr  TF, TAo, TS 14 Fr  TF, TA 18 Fr  TF, TA 18 Fr/19 Fr  TF, TA, TAo 14 Fr/16 Fr  TF, TA, TS 18 Fr/20 Fr  CE mark (years)  2011  2017  Awaited  2017  2013  2011 (AS) 2013 (AR)  2012  2014  NA  Specific advantages  Low PPM requirement  Resheathable up to 70% of deployment  Resheathable up to 85% deployment. PTFE skirt to reduce PVL. Motorized delivery system  Resheathable up to 80% deployment Double layer porcine pericardial skirt  Resheathable up to 80% deployment. Upcoming RCT data in low risk population  Active fixation for use in AR  Resheathable up to 85% deployment  External skirt to reduce PVL. Upcoming RCT data in low risk population  Experience in bicuspid valve population in China; reduced cost    Acurate (Boston Scientific)  Allegra (NVT)  Centera (Edwards)  Evolut PRO (Medtronic)  Evolut R (Medtronic)  JenaValve (JenaValve)  Portico (St Jude)  Sapien 3 (Edwards)  VenusA (Venus Medtech)                      Design (leaflets, frame and delivery)  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Cobalt-chromium Balloon-expandble  Porcine pericardium Nitinol Self-expanding  Delivery routes and sheath size  TF, TA, TS 18 Fr/19 Fr  TF 18 Fr  TF, TS 14 Fr  TF, TAo, TS 16 Fr  TF, TAo, TS 14 Fr  TF, TA 18 Fr  TF, TA 18 Fr/19 Fr  TF, TA, TAo 14 Fr/16 Fr  TF, TA, TS 18 Fr/20 Fr  CE mark (years)  2011  2017  Awaited  2017  2013  2011 (AS) 2013 (AR)  2012  2014  NA  Specific advantages  Low PPM requirement  Resheathable up to 70% of deployment  Resheathable up to 85% deployment. PTFE skirt to reduce PVL. Motorized delivery system  Resheathable up to 80% deployment Double layer porcine pericardial skirt  Resheathable up to 80% deployment. Upcoming RCT data in low risk population  Active fixation for use in AR  Resheathable up to 85% deployment  External skirt to reduce PVL. Upcoming RCT data in low risk population  Experience in bicuspid valve population in China; reduced cost  AR, aortic regurgitation; AS, aortic stenosis; PPM, permanent pacemaker; PVL, paravalvular leak; TA, transapical; TAo, transaortic; TF, transfemoral; TS, trans-subclavian. There are few studies allowing direct comparison between current valve systems. The CHOICE study randomized patients to the Sapien XT or CoreValve, demonstrating similar mortality but a higher risk of PVL (>mild) with CoreValve.38 Both valves have now been superseded by newer versions, however, and a contemporary RCT of the S3 and Evolut R has not been conducted. The REPRISE III trial compared the mechanically-expanded Lotus Valve and the CoreValve, demonstrating non-inferiority of the Lotus Valve in terms of safety and a significant reduction in moderate and severe PVL (0.9% vs. 6.8%, P < 0.01), at the cost of higher pacemaker requirement (35.5% vs. 19.6%, P < 0.001).39 Meanwhile, the ongoing SCOPE I and SCOPE II studies will provide similar comparisons of the Acurate valve with the S3 and Evolut CoreValve systems, respectively. Further investigator-led studies into the range of new valve systems will be valuable to compare efficacy, durability and complication profiles. Ongoing challenges Despite the indisputable success of TAVI, there are numerous remaining challenges. It is important to look beyond early technical success and short-medium term safety, which have been the focus of most studies to date. A recent European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) statement, the internationally agreed VARC-2 endpoints, and a recent consensus document from the VIVIV group provide important standardization for trials focusing on long-term durability and late complications.40–42 Ultimately, the aim should be to not only match SAVR but also set a new gold standard for patients undergoing valve intervention. Valve durability and function Structural valve deterioration (SVD) is defined by permanent intrinsic changes of the valve (calcification, pannus, and leaflet failure) leading to degeneration and/or dysfunction, which in turn may result in valvular stenosis or intra-prosthetic regurgitation.41 The risk of SVD is heavily influenced by valve design and patient age at the time of implantation. Durable long-term outcomes have been reported for surgical bioprosthetic valves, but freedom from SVD at 15 years ranges from 67% in patients aged <60 years to 92% in patients >70 years.43,44 Valve design may influence SVD unpredictably—notable examples of early valve failure due to intrinsic design problems are the Ionescu-Shiley pericardial tissue valve and the St. Jude Toronto SPV valve.45 Concerns that transcatheter valves might suffer from early SVD have not so far materialized, with 5 years outcomes from PARTNER I showing that SVD requiring intervention is rare (∼0.2%).46 Moderate or severe transvalvular regurgitation developed in 3.7% after TAVI, increasing over time. In a multicentre registry study of 1521, TAVI patients over mean echocardiographic follow-up of 20 ± 13 months, 4.5% of patients developed an increase in mean transvalvular gradient of ≥10 mmHg, with a mean increase of 0.30 ± 4.99 mmHg/year.47 Independent predictors of a rising gradient were absence of anticoagulation, a valve-in-valve procedure, use of a 23 mm valve and greater body mass index. While this medium term follow-up is reassuring, studies of surgical bioprostheses indicate that SVD before 10 years is rare, and continued close follow-up is essential to establish the long-term durability of transcatheter valves. By the early 2020s, data will be available for a relatively small number of patients who received first generation valves. Establishing durability in large cohorts and determining the relative freedom from SVD of different valve designs will take longer but is of crucial importance as TAVI moves into lower age groups. In addition, development of transcatheter strategies for treatment of degenerated TAVI valves (i.e. redo-TAVI) is a current research and engineering priority. Although SVD appears rare, there may be a signal of concern regarding subclinical leaflet thrombosis.48 Identified on CT imaging in 10–15% of TAVI patients, this phenomenon that manifests as leaflet thickening and reduced leaflet motion has been correlated with thrombus. Although risk factors for subclinical leaflet thrombosis are not clearly identified, regional stent frame under-expansion has been associated with an increased risk of leaflet thickening, while post-dilatation of self-expanding valves and a supra-annular valve position seem to reduce its frequency.49 Furthermore, oral anticoagulant (OAC) therapy (but not dual antiplatelet therapy, DAPT) seems to prevent and resolve the phenomenon.39 Recent analysis of 931 patients in the combined RESOLVE-SAVORY registries demonstrates that valve dysfunction (aortic valve gradient >20 mmHg) remains uncommon but occurs more frequently in patients with valve thrombosis (14% vs. 1%, P < 0.0001).50 Even though leaflet thrombosis was associated with an increased risk of transient ischaemic attack (4.18 vs. 0.6 per 100 person years, P = 0.0005), these findings must be interpreted with caution due to temporal separation between the CT and the clinical event. Ongoing studies of different regimes of OAC or anti-platelet therapy following TAVI are keenly awaited and long-term OAC may prove necessary for some patients. Stroke Stroke is a devastating complication of TAVI and associated with a 5–10 fold increased risk of short-term mortality.51,52 Patients undergoing TAVI are at increased risk of embolic stroke during the procedure (associated primarily with valve positioning and deployment) and during a post-procedural phase lasting weeks to months.53 The risk of stroke in PARTNER I was over twice as high in the TAVI cohort compared with SAVR (5.5% vs. 2.4% at 30 days, P = 0.04), although this difference diminished over time and has not been observed in subsequent trials. The incidence of stroke 30 days following TAVI was 3.1% in PARTNER IIA and significantly lower than after SAVR in SURTAVI (3.3% TAVI vs. 5.4% SAVR, P = 0.031). Large scale data from the TVT registry report a rate of clinically significant stroke of 2.5% at 30 days and 4.1% at 1 year.54 Strategies to reduce stroke have focused on embolic protection and anticoagulation. Following TAVI up to 75% of patients have new ischaemic lesions on diffusion-weighted cerebral MRI, making embolic protection intuitively attractive.55 The CLEAN-TAVI trial randomized 100 patients undergoing TAVI to the Montage filter or control, and demonstrated a reduction in the primary endpoint of cerebral infarct volume.56 In contrast, the SENTINEL trial (Sentinel device, Claret Medical) found a trend towards reduced infarct volume (that did not reach statistical significance) and no difference in the rate of clinical stroke.57 A recent observational series has reported stroke reduction with the Sentinel device (4.6–1.4%, P = 0.03), but this requires further validation.58 Several trials are ongoing, including PROTECT-TAVI (Sentinel) and REFLECT (TriGuard) (Figure 2). Although new imaging lesions have been linked to deterioration in neurocognitive status, they do not represent stroke, and the clinical benefits of embolic protection remain to be clearly established. The role of antiplatelet and OAC agents to prevent stroke following TAVI is currently ill-defined, but the evidence base is evolving rapidly. Coronary disease, recent percutaneous intervention, and AF are common in the TAVI population, and between 10% and 30% of patients have new-onset AF following TAVI leading to increased risk of stroke.59,60 Although DAPT is routinely used post-TAVI, this is not supported by strong evidence. The recent ARTE trial compared DAPT with aspirin monotherapy post-TAVI in 222 patients and demonstrated that the composite of death, MI, stroke or transient ischaemic attack, or major or life-threatening bleeding tended to occur less frequently in the aspirin group (7.2% vs. 15.3%, P = 0.065), and that aspirin alone led to a reduction in major or life-threatening bleeding (3.6% vs. 10.8%, P = 0.038).61 Three further upcoming trials will inform the use of OAC following TAVI (Figure 2). The GALILEO RCT (NCT02556203) is comparing Rivaroxaban plus Aspirin with DAPT (Aspirin and Clopidogrel). The ATLANTIS study (NCT02664649) is randomising patients with an indication for OAC to a vitamin K antagonist or Apixaban, and those without to either DAPT, a single antiplatelet agent or Apixaban. Finally, the POPULAR-TAVI trial (NCT02247128) is investigating the additional role of Clopidogrel to OAC in patients who require anticoagulation, and the merits of DAPT against aspirin monotherapy in those without an indication for anticoagulation. Permanent pacemaker implantation Interference with the cardiac conduction system is common after TAVI, with new left bundle branch block (LBBB) or complete atrioventricular block necessitating PPM implantation in ∼5–35% of patients.62,63 The impact of new conduction disease is controversial: PARTNER I identified an increased incidence of mortality/repeat hospitalization at 1 year in patients requiring a PPM (42 vs. 32.6%, P = 0.007), with a similar increase in mortality associated with PPM implantation in the TVT registry (24.1% vs. 19.6%, hazard ratio 1.31; 95% CI 1.09–1.58).63,64 Although this adverse effect has not been observed in other studies, the consequences of long-term right ventricular pacing are well-documented and preferably avoided, especially in younger patients with longer life-expectancy.65,66 Patient, procedure and device-related risk factors have been identified. Those at increased risk of conduction disturbance include older, male patients, and those with pre-existing conduction disease (especially right bundle branch block), a small outflow tract, or calcification of the aortic or mitral valve annulus.67 Procedural risk factors include valve oversizing, deep implantation, and balloon post-dilatation. Valve design also has a major impact—the CoreValve and Lotus valve have the highest rates of PPM requirement (30–40% for the latter),68,69 whereas the Acurate NEO (Boston Scientific, previously Symetis) is associated with PPM rates as low as 2.3% (10.3% new LBBB). Further work is required to optimize valve design, implantation technique and device selection to reduce PPM requirements while ensuring minimal incidence of PVL. Vascular access Transfemoral TAVI now dominates as the safest and simplest vascular access route, and is associated with improved outcomes compared with other approaches. Facilitated by smaller delivery systems and expandable sheath or sheath-less approach, transfemoral valve delivery is achievable in at least 90% of cases, and the incidence of major vascular complications has reduced to ∼2% in contemporary practice. However, transfemoral access is not viable for a small minority of patients and alternative routes are required. Multiple possible strategies have been reported, including subclavian/axillary, carotid, transapical, direct aortic, and transcaval access. Although not all routes have been directly compared, retrospective data suggest that subclavian access is the safest choice for non-femoral access, with outcomes similar to the transfemoral approach.70 In future, direct aortic access via the inferior vena cava (transcaval approach) may be preferred, with recent series demonstrating feasibility in 99% of cases (n = 100), albeit with reported rates of retroperitoneal or life-threatening bleeding of 24% and 7%, respectively.71 Bicuspid aortic valve Bicuspid aortic valve anatomy is found in 0.5–2.0% of the population, and AS affecting a bicuspid valve is the most common indication for SAVR in patients <70 years of age. Bicuspid AS is associated with specific anatomic challenges relevant to TAVI; heavy valve calcification, an eccentrically shaped annulus, and a horizontal, dilated aorta. While technically feasible, the number of patients with BAV who have undergone TAVI is small, and this group demonstrate significant rates of moderate to severe PVL (∼10%) and major vascular complications.72 Patients with BAV are at specific risk of aortic root complications due to heavy calcification or associated aortopathy. For these reasons, BAV has been an exclusion criteria in many TAVI trials. However, outcomes are improving with new devices: in the Bicuspid TAVR registry of 301 patients, moderate or severe PVL was less frequent with new devices (Sapien 3 or Lotus) compared with the CoreValve or Sapien XT (0.0% vs. 8.5%, P = 0.002).73 The same registry also reported no significant difference in clinical outcomes or rates of PVL between Type 0 (’pure’) and Type I (single raphe) anatomy, in contrast to earlier studies in which Type I BAV was a risk factor for PVL.72,74 Further reductions in the incidence of PVL and aortic root complications in patients with challenging anatomy are an important next step in the evolution of TAVI. Infective endocarditis Infective endocarditis affects approximately 0.5–3% of patients within the first year following TAVI and has an in-hospital mortality of 30–60%.75,76 Management is extremely challenging: many patients have been previously deemed unfit for cardiac surgery and the majority are therefore treated with antibiotic therapy alone.75,77 TAVI-related endocarditis is most commonly caused by Enterococcus species, which gain access to the circulation from the gastrointestinal or genitourinary tract. Given the difficulties of treatment, prevention is the logical focus. TAVI recipients may benefit from expanded use of antibiotic prophylaxis to cover gastrointestinal and genitourinary procedures, and this warrants further research. Rigorous sterility is of paramount importance, particularly when TAVI is conducted in the catheter laboratory environment, although procedural location has not been found to be a specific risk factor for the development of endocarditis.77 Valve design may also play a role—the Xeltis valve, a bioabsorbable polymer scaffold, which is endothelialized and eventually replaced by recipient tissue, is in pre-clinical development and may reduce risk of bacterial adherence and consequent endocarditis.78 Current clinical guidelines The central position of TAVI in the contemporary management of AS has been underwritten by the ESC/EACTS 2017 guidelines for the management of valvular heart disease (Figure 3; Table 3),2 which not only outline straightforward pointers in favour of TAVI or SAVR, but also afford considerable discretion to the treating Heart Team. Patients at low surgical risk (STS < 4%) with no specific features to favour TAVI (Table 3) should undergo SAVR. For all others, however, the choice between TAVI and SAVR should be based on the risk: benefit ratio for a given individual and their technical suitability for either procedure. Specific factors in favour of TAVI include the presence of severe comorbidity, age ≥75 years, previous cardiac surgery, frailty, restricted mobility, conditions likely to affect rehabilitation, and aortic anatomy permitting transfemoral delivery. Table 3 Considerations for the Heart Team in the choice between TAVI and surgical aortic valve replacement   Favours TAVI  Favours SAVR  Clinical characteristics   STS/EuroSCORE II <4%    +   STS/EuroSCORE II ≥4%  +     Presence of severe comorbidity not adequately reflected by scores  +     Age <75    +   Age ≥75  +     Previous cardiac surgery  +     Frailty  +     Restricted mobility and conditions that may affect rehabilitation  +     Suspicion of endocarditis    +  Anatomical and technical aspects   Favourable transfemoral access  +     Unfavourable access (any) for TAVI    +   Sequelae of chest radiation  +     Porcelain aorta  +     Presence of intact CABG at risk when sternotomy is performed  +     Expected patient-prosthesis mismatch  +     Severe chest deformation or scoliosis  +     Short distance between coronary ostia and aortic valve annulus    +   Size of aortic valve annulus out of range for TAVI    +   Aortic root morphology unfavourable for TAVI    +   Valve morphology (bicuspid, degree, or pattern of calcification) unfavourable for TAVI    +   Presence of thrombi in the aorta    +  Cardiac conditions where concomitant intervention should be considered   Severe CAD requiring revascularization by CABG    +   Severe primary mitral valve disease, which could be treated surgically    +   Severe tricuspid disease    +   Aneurysm of the ascending aorta    +   Septal hypertrophy requiring myectomy    +    Favours TAVI  Favours SAVR  Clinical characteristics   STS/EuroSCORE II <4%    +   STS/EuroSCORE II ≥4%  +     Presence of severe comorbidity not adequately reflected by scores  +     Age <75    +   Age ≥75  +     Previous cardiac surgery  +     Frailty  +     Restricted mobility and conditions that may affect rehabilitation  +     Suspicion of endocarditis    +  Anatomical and technical aspects   Favourable transfemoral access  +     Unfavourable access (any) for TAVI    +   Sequelae of chest radiation  +     Porcelain aorta  +     Presence of intact CABG at risk when sternotomy is performed  +     Expected patient-prosthesis mismatch  +     Severe chest deformation or scoliosis  +     Short distance between coronary ostia and aortic valve annulus    +   Size of aortic valve annulus out of range for TAVI    +   Aortic root morphology unfavourable for TAVI    +   Valve morphology (bicuspid, degree, or pattern of calcification) unfavourable for TAVI    +   Presence of thrombi in the aorta    +  Cardiac conditions where concomitant intervention should be considered   Severe CAD requiring revascularization by CABG    +   Severe primary mitral valve disease, which could be treated surgically    +   Severe tricuspid disease    +   Aneurysm of the ascending aorta    +   Septal hypertrophy requiring myectomy    +  Reproduced with permission from Baumgartner et al.2 CABG, coronary artery bypass grafting; CAD, coronary artery disease. Table 3 Considerations for the Heart Team in the choice between TAVI and surgical aortic valve replacement   Favours TAVI  Favours SAVR  Clinical characteristics   STS/EuroSCORE II <4%    +   STS/EuroSCORE II ≥4%  +     Presence of severe comorbidity not adequately reflected by scores  +     Age <75    +   Age ≥75  +     Previous cardiac surgery  +     Frailty  +     Restricted mobility and conditions that may affect rehabilitation  +     Suspicion of endocarditis    +  Anatomical and technical aspects   Favourable transfemoral access  +     Unfavourable access (any) for TAVI    +   Sequelae of chest radiation  +     Porcelain aorta  +     Presence of intact CABG at risk when sternotomy is performed  +     Expected patient-prosthesis mismatch  +     Severe chest deformation or scoliosis  +     Short distance between coronary ostia and aortic valve annulus    +   Size of aortic valve annulus out of range for TAVI    +   Aortic root morphology unfavourable for TAVI    +   Valve morphology (bicuspid, degree, or pattern of calcification) unfavourable for TAVI    +   Presence of thrombi in the aorta    +  Cardiac conditions where concomitant intervention should be considered   Severe CAD requiring revascularization by CABG    +   Severe primary mitral valve disease, which could be treated surgically    +   Severe tricuspid disease    +   Aneurysm of the ascending aorta    +   Septal hypertrophy requiring myectomy    +    Favours TAVI  Favours SAVR  Clinical characteristics   STS/EuroSCORE II <4%    +   STS/EuroSCORE II ≥4%  +     Presence of severe comorbidity not adequately reflected by scores  +     Age <75    +   Age ≥75  +     Previous cardiac surgery  +     Frailty  +     Restricted mobility and conditions that may affect rehabilitation  +     Suspicion of endocarditis    +  Anatomical and technical aspects   Favourable transfemoral access  +     Unfavourable access (any) for TAVI    +   Sequelae of chest radiation  +     Porcelain aorta  +     Presence of intact CABG at risk when sternotomy is performed  +     Expected patient-prosthesis mismatch  +     Severe chest deformation or scoliosis  +     Short distance between coronary ostia and aortic valve annulus    +   Size of aortic valve annulus out of range for TAVI    +   Aortic root morphology unfavourable for TAVI    +   Valve morphology (bicuspid, degree, or pattern of calcification) unfavourable for TAVI    +   Presence of thrombi in the aorta    +  Cardiac conditions where concomitant intervention should be considered   Severe CAD requiring revascularization by CABG    +   Severe primary mitral valve disease, which could be treated surgically    +   Severe tricuspid disease    +   Aneurysm of the ascending aorta    +   Septal hypertrophy requiring myectomy    +  Reproduced with permission from Baumgartner et al.2 CABG, coronary artery bypass grafting; CAD, coronary artery disease. Figure 3 View largeDownload slide European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines for the management of severe aortic stenosis. Surgical aortic valve replacement is indicated in asymptomatic patients if there is left ventricular systolic dysfunction due to aortic stenosis (ejection fraction <50%) (Class I, level of evidence C). Risk stratification by exercise testing can be performed in those with normal ejection fraction—surgical aortic valve replacement is indicated if symptoms develop (or blood pressure drops) during exercise. In those with a normal exercise test (or unable to exercise), evaluation of predictors of progression (peak velocity ≥5.5 m/s, severe valve calcification + increase in peak velocity >0.3 m/s/year, elevated neurohormonal levels, or severe pulmonary hypertension), and surgical risk should guide the choice between activate surveillance and surgical aortic valve replacement. In patients with symptomatic severe aortic stenosis, there is a Class I, level of evidence B recommendation for aortic valve intervention. Surgical aortic valve replacement is the default in those at low risk with no characteristics favouring transcatheter aortic valve implantation. Heart Team evaluation to assess suitability and risk-benefit ratio of transcatheter aortic valve implantation vs. surgical aortic valve replacement is appropriate in all other patients. Reproduced with permission from Baumgartner et al.2 AS, aortic stenosis; LVEF, left ventricular ejection fraction; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation. Figure 3 View largeDownload slide European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines for the management of severe aortic stenosis. Surgical aortic valve replacement is indicated in asymptomatic patients if there is left ventricular systolic dysfunction due to aortic stenosis (ejection fraction <50%) (Class I, level of evidence C). Risk stratification by exercise testing can be performed in those with normal ejection fraction—surgical aortic valve replacement is indicated if symptoms develop (or blood pressure drops) during exercise. In those with a normal exercise test (or unable to exercise), evaluation of predictors of progression (peak velocity ≥5.5 m/s, severe valve calcification + increase in peak velocity >0.3 m/s/year, elevated neurohormonal levels, or severe pulmonary hypertension), and surgical risk should guide the choice between activate surveillance and surgical aortic valve replacement. In patients with symptomatic severe aortic stenosis, there is a Class I, level of evidence B recommendation for aortic valve intervention. Surgical aortic valve replacement is the default in those at low risk with no characteristics favouring transcatheter aortic valve implantation. Heart Team evaluation to assess suitability and risk-benefit ratio of transcatheter aortic valve implantation vs. surgical aortic valve replacement is appropriate in all other patients. Reproduced with permission from Baumgartner et al.2 AS, aortic stenosis; LVEF, left ventricular ejection fraction; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation. The ESC/EACTS guidelines advocate centralized care, with a Class I recommendation that TAVI is performed in a Heart Valve Centre with on-site surgery.2 The role of the Heart Team is core, in practice comprising two interventional cardiologists, two cardiac surgeons, and a cardiac imaging specialist, as well as input from care of the elderly, anaesthetics, and nurse specialists.79 A full spectrum of imaging modalities should be available, and outcomes should be transparently reported and publicly available. These recommendations may prove controversial: some TAVI procedures in Germany are already being performed at non-surgical sites.80 However, a direct relationship between higher case volume and lower mortality has been demonstrated in the same country, with an in-hospital mortality of 5.2% (95% CI 4.8–5.7) in the highest volume quintile vs. 7.6% (7.1–8.2) in the lowest volume quintile.81,82 The minimum number of cases required to fall below average mortality (6.6%) was 157/year. These data support the centralized Heart Valve Centre model, with access to the full spectrum of surgical and transcatheter valve interventions on-site, as defined in current ESC guidelines.2 This model incorporates side-by-side decision-making with surgical colleagues, alongside audit of outcomes and training of a new generation of structural interventionists. Importantly, it will also promote a critical mass of expertise as percutaneous treatment options for mitral and tricuspid valve disease emerge. The future In the context of an expanding, ageing population, the number of TAVI procedures is set to grow 4–10-fold over the next decade.83,84 In many countries, the challenges of cost and infrastructural development are already the rate-limiting step to implementation of TAVI, rather than the clinical evidence base. Transfemoral delivery and a simplified procedure are increasing availability, but the maintenance of high quality decision-making, excellent outcomes and specialist training in a Heart Valve Centre are critical. Meeting the logistic challenge of delivering TAVI care will require a new cadre of structural interventionists, derived through cardiological, surgical, or hybrid training routes. The relative cost of devices will come under increasing scrutiny in a competing market of valves with broad clinical equivalence, and this will improve affordability and overall cost-effectiveness. In 2018, TAVI is already a refined, low-risk procedure for aortic valve replacement with evidence of intermediate durability. Within a few years, transfemoral TAVI is likely to demonstrate non-inferiority to SAVR in patients at low procedural risk, and may show benefit over active surveillance in the asymptomatic population. More challenging is the transition to younger patients: TAVI must demonstrate durability equivalent to surgical bioprostheses, and options will be required for dealing with SVD when it occurs. Ongoing valve innovation is necessary, in particular to achieve comparable outcomes for challenging anatomy (particularly BAV). Specific patient subsets are likely to benefit from different antiplatelet and OAC combinations, and these remain to be defined. Reducing the requirement for PPM implantation while ensuring minimal incidence of PVL is a further important requirement before TAVI can be widely used in younger patients. These challenges are not insurmountable. TAVI has deftly navigated infancy and adolescence: as it comes of age its future looks extremely bright. Conflict of interest: K.H. is a clinical proctor for Edwards Lifesciences. A.L. is a consultant for Medtronic and Abbott Vascular and has received unrestricted research grants from Edwards Lifesciences and Medtronic. L.S. has received consulting fees and institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and Symetis. B.D.P. has received unrestricted research grants from Edwards Lifesciences and lecture fees from Edwards Lifesciences, Symetis and Boston Scientific. References 1 Cribier A, Eltchaninoff H, Bash A, Borenstein N, Tron C, Bauer F, Derumeaux G, Anselme F, Laborde F, Leon MB. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation  2002; 106: 3006– 3008. 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Transcatheter aortic valve implantation: current status and future perspectives

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Oxford University Press
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.
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0195-668X
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1522-9645
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Abstract

Abstract In the 16 years since the first pioneering procedure, transcatheter aortic valve implantation (TAVI) has come of age and become a routine strategy for aortic valve replacement, increasingly performed under conscious sedation via transfemoral access. Simplification of the procedure, accumulation of clinical experience, and improvements in valve design and delivery systems have led to a dramatic reduction in complication rates. These advances have allowed transition to lower risk populations, and outcome data from the PARTNER 2A and SURTAVI trials have established a clear evidence base for use in intermediate risk patients. Ongoing studies with an expanding portfolio of devices seem destined to expand indications for TAVI towards lower risk, younger and asymptomatic populations. In this article, we outline recent advances, new devices and current guidelines informing the use of TAVI, and describe remaining uncertainties that need to be addressed. Aortic stenosis, Aortic valve replacement, Computed tomography, Transcatheter aortic valve implantation, Transcatheter aortic valve replacement, TAVI, TAVR Introduction Since the first procedure in 2002, transcatheter aortic valve implantation (TAVI) has revolutionized the management of aortic stenosis (AS)1 and become the standard of care for patients with AS at prohibitive surgical risk, and the preferred treatment for many intermediate and high risk elderly patients.2 Its clinical and market impact cannot be overstated; over 300 000 patients have now received a transcatheter aortic valve in a global market worth $2 billion per annum. Newer generations of transcatheter valve design and optimization of patient selection, procedural planning and technique have driven stepwise improvements in efficacy and reduction in complication rates. The breakaway success of TAVI has been underpinned by the combination of patients in need and collaboration between cardiologists, surgeons, clinical investigators, and the device industry. While surgical aortic valve replacement (SAVR), first performed in 1960, is an established and durable option for AS, up to a third of patients are deemed unsuitable due to excess procedural risk.3 A lack of alternative therapeutic options led to the conception, development, and clinical application of the balloon-expandable Cribier-Edwards transcatheter valve. The pioneering success of the first procedure has since been translated into routine clinical practice through a series of landmark clinical trials enrolling over 15 000 patients [including eight randomized controlled trials (RCTs)] since 2007. As TAVI comes of age, there are new frontiers and potential hurdles. Percutaneous treatment is challenging SAVR in lower risk patient cohorts, and ongoing trials in patients with asymptomatic AS and moderate AS with heart failure may overturn traditional indications for valve replacement. However, questions remain over long-term valve durability, stroke risk, and complications such as haemorrhage, conduction abnormalities, paravalvular leak (PVL), and infective endocarditis. In this context, we review the state-of-the-art in TAVI, providing a current perspective on recent and ongoing trials, the contemporary device portfolio, clinical guidelines and strategies to further reduce complication rates. Current perspectives on transcatheter aortic valve implantation A decade of clinical experience with TAVI has led to substantial simplification of the procedure. Improved valve and delivery catheter technologies have been transformative. Newer generation devices offer improved sizing, deliverability and positioning compared with earlier forerunners, and valve implantation via transfemoral access is now achievable in approximately 90% of patients using expandable sheaths and/or atraumatic, small-bore delivery catheters. Pre-procedural planning and valve selection have been advanced by standardized computed tomography (CT) imaging, which has emerged as the optimal modality for assessing vascular access, annular dimensions and valve morphology, and predicting potential complications. An increasing proportion of TAVI cases worldwide are now performed using a ‘minimalist’ approach, under conscious sedation (CS), local anaesthesia, and transthoracic echocardiographic guidance.4 Conscious sedation is used routinely for transfemoral TAVI across much of Europe and has the potential advantages of reduced procedural time, faster recovery and reduced cost, but is associated with reduced use of peri-procedural transoesophageal echocardiography (TOE). While valve deployment and assessment of residual aortic regurgitation can be guided by fluoroscopy, aortography, haemodynamic measurement and standby transthoracic imaging, lack of TOE guidance is associated with increased contrast use and greater risk of post-procedural aortic regurgitation.4,5 This must be weighed against emerging US propensity-matched data from almost 11 000 patients undergoing transfemoral TAVI, which demonstrate that CS is associated with a shorter hospital stay and reduced short-term mortality.6 Above all, the chosen approach should be tailored for individual patients: for example, a limited post-procedural TOE to exclude PVL may assist in those with chronic kidney disease where contrast use is limited. Intracardiac echocardiography is also a valuable tool in specific high-risk patients where continuous echocardiographic guidance is desirable.7 This evolution of TAVI has led to a reduction in procedural mortality and major complication rates. Data from the UK TAVI registry (Figure 1) demonstrate a large reduction in mortality prior to hospital discharge (9.09% in 2008, 1.84% in 20168), and progressive reductions in mortality and complication rates have also been observed in registry studies from France, Germany, Japan and the USA.10–13 Between 2008 and 2016 the incidence of stroke fell from 3.4% to 2.2%, requirement for haemofiltration from 6.4% to 0.9%, and tamponade from 5.3% to 1.4%. These improvements have been associated with reduced length of stay, with median time from procedure to discharge falling from 130 h (2013) to 64 h (2016). This is likely to fall further with structured early discharge programmes. For example, preliminary outcomes from the Vancouver 3M Clinical Pathway show safe one-day discharge in up to 80% of patients after transfemoral TAVI, achieved by a minimalist procedure, avoidance of routine intensive care and use of criteria-led discharge.14 In a US cohort of 360 patients undergoing uncomplicated transfemoral TAVI with a Sapien valve, male sex, absence of atrial fibrillation (AF), lower creatinine, and young age were factors associated with safe next day discharge.15 Figure 1 View largeDownload slide Temporal change in complication rates in patients undergoing transcatheter aortic valve implantation. Over time, there has been a major reduction in the incidence of in-hospital mortality (A), serious complications including tamponade (B), post-procedural dialysis (C), and stroke prior to discharge (D). Data from British Cardiovascular Intervention Society TAVI Audit.8,9 Figure 1 View largeDownload slide Temporal change in complication rates in patients undergoing transcatheter aortic valve implantation. Over time, there has been a major reduction in the incidence of in-hospital mortality (A), serious complications including tamponade (B), post-procedural dialysis (C), and stroke prior to discharge (D). Data from British Cardiovascular Intervention Society TAVI Audit.8,9 Despite these improvements, global use of TAVI is patchy with several barriers to wider geographical use. First, device cost is currently prohibitive (>$30 000 in the USA) and international uptake correlates strongly with healthcare spend.16 Device costs have risen over time and seem unlikely to stabilize until, there are more competing valves available on the market. Second, infrastructural development in countries where there is no existing Heart Valve Centre model stretches scarce capital resources. Third, in populations with specific anatomic challenges (for example smaller ilio-femoral vessels, as in China and Asia) further valve innovation and specific studies are required to demonstrate equivalent outcomes to those seen in European and US trials. Nevertheless, the potential scope for future TAVI growth is well illustrated in Germany, where the number of patients undergoing TAVI exceeded SAVR by 2014 (while surgical numbers remained stable).17 Transcatheter aortic valve implantation for intermediate and low risk patients Two landmark RCTs have recently reported outcomes of TAVI in comparison with SAVR in elderly patients with severe symptomatic AS at intermediate surgical risk (Table 1).18,19 PARTNER 2A randomized 2032 patients with a Society of Thoracic Surgeons (STS) predicted mortality risk of 4–10% to TAVI with the Sapien XT valve, or SAVR.18 The mean age was 82 years with a mean STS score of 5.8%, well below that of the high risk PARTNER I and CoreValve US Pivotal trials (where mean STS scores were 12% and 7.4%, respectively).20,21 At 2 years, PARTNER 2A found no significant difference in the primary endpoint, a composite of death from any cause or disabling stroke. Furthermore, the transfemoral TAVI subset had a significantly lower rate of death or disabling stroke than those undergoing SAVR, a finding confirmed in a subsequent meta-analysis of the PARTNER 1A, US CoreVALVE, NOTION, and PARTNER 2A trials.22 Table 1 Randomized trials of TAVI vs. SAVR in intermediate risk patients with severe symptomatic AS Study  Design  Size  Predicted STS (%)  Age/STS  Trial arms  Outcomes  Complication profile  PARTNER 2A  RCT  2032  4–10  Mean age 82 years Mean STS 5.8%  TAVI (Sapien XT) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 19.3% TAVI vs. 21.1% SAVR, HR for TAVI 0.89, 95% CI 0.73–1.09; P = 0.25  TAVI: higher rate of major vascular complications (7.9% vs 5.0%); lower rates of life-threatening bleeding (10.4% vs 43.4%) and new atrial fibrillation (9.1% vs 26.4%) (all p<0.01)  SURTAVI  RCT  1077  3–15  Mean age 79.8 years Mean STS 4.5%  TAVI (CoreValve/Evolut R) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 12.6% TAVI vs. 14.0% SAVR, 95% credible interval −5.2 to 2.3%; P > 0.999  TAVI: higher rate of major vascular complications (6.0 vs. 1.1%), residual moderate or severe paravalvular leak (5.3% vs. 0.6%), and pacemaker implantation (25.9% vs. 6.6%); lower rates of acute kidney injury (1.7% vs. 4.4%) (differences outside 95% credible interval)  Study  Design  Size  Predicted STS (%)  Age/STS  Trial arms  Outcomes  Complication profile  PARTNER 2A  RCT  2032  4–10  Mean age 82 years Mean STS 5.8%  TAVI (Sapien XT) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 19.3% TAVI vs. 21.1% SAVR, HR for TAVI 0.89, 95% CI 0.73–1.09; P = 0.25  TAVI: higher rate of major vascular complications (7.9% vs 5.0%); lower rates of life-threatening bleeding (10.4% vs 43.4%) and new atrial fibrillation (9.1% vs 26.4%) (all p<0.01)  SURTAVI  RCT  1077  3–15  Mean age 79.8 years Mean STS 4.5%  TAVI (CoreValve/Evolut R) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 12.6% TAVI vs. 14.0% SAVR, 95% credible interval −5.2 to 2.3%; P > 0.999  TAVI: higher rate of major vascular complications (6.0 vs. 1.1%), residual moderate or severe paravalvular leak (5.3% vs. 0.6%), and pacemaker implantation (25.9% vs. 6.6%); lower rates of acute kidney injury (1.7% vs. 4.4%) (differences outside 95% credible interval)  Table 1 Randomized trials of TAVI vs. SAVR in intermediate risk patients with severe symptomatic AS Study  Design  Size  Predicted STS (%)  Age/STS  Trial arms  Outcomes  Complication profile  PARTNER 2A  RCT  2032  4–10  Mean age 82 years Mean STS 5.8%  TAVI (Sapien XT) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 19.3% TAVI vs. 21.1% SAVR, HR for TAVI 0.89, 95% CI 0.73–1.09; P = 0.25  TAVI: higher rate of major vascular complications (7.9% vs 5.0%); lower rates of life-threatening bleeding (10.4% vs 43.4%) and new atrial fibrillation (9.1% vs 26.4%) (all p<0.01)  SURTAVI  RCT  1077  3–15  Mean age 79.8 years Mean STS 4.5%  TAVI (CoreValve/Evolut R) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 12.6% TAVI vs. 14.0% SAVR, 95% credible interval −5.2 to 2.3%; P > 0.999  TAVI: higher rate of major vascular complications (6.0 vs. 1.1%), residual moderate or severe paravalvular leak (5.3% vs. 0.6%), and pacemaker implantation (25.9% vs. 6.6%); lower rates of acute kidney injury (1.7% vs. 4.4%) (differences outside 95% credible interval)  Study  Design  Size  Predicted STS (%)  Age/STS  Trial arms  Outcomes  Complication profile  PARTNER 2A  RCT  2032  4–10  Mean age 82 years Mean STS 5.8%  TAVI (Sapien XT) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 19.3% TAVI vs. 21.1% SAVR, HR for TAVI 0.89, 95% CI 0.73–1.09; P = 0.25  TAVI: higher rate of major vascular complications (7.9% vs 5.0%); lower rates of life-threatening bleeding (10.4% vs 43.4%) and new atrial fibrillation (9.1% vs 26.4%) (all p<0.01)  SURTAVI  RCT  1077  3–15  Mean age 79.8 years Mean STS 4.5%  TAVI (CoreValve/Evolut R) vs. SAVR  No significant difference in the primary endpoint (composite of death from any cause or disabling stroke) at 2 years 12.6% TAVI vs. 14.0% SAVR, 95% credible interval −5.2 to 2.3%; P > 0.999  TAVI: higher rate of major vascular complications (6.0 vs. 1.1%), residual moderate or severe paravalvular leak (5.3% vs. 0.6%), and pacemaker implantation (25.9% vs. 6.6%); lower rates of acute kidney injury (1.7% vs. 4.4%) (differences outside 95% credible interval)  SURTAVI enrolled 1746 intermediate risk patients (estimated surgical mortality 3–15%) at 87 centres in Europe, the USA and Canada.19 Patients were randomized to TAVI using the CoreValve system (CoreValve 84%, next generation Evolut R 16%) or SAVR. The mean age was 79.8 years with a mean STS score of 4.5%. As in PARTNER 2A, SURTAVI found no significant difference in the primary endpoint (composite of death from any cause or disabling stroke) between TAVI and SAVR at 2 years. Further support for TAVI in intermediate risk patients has come from observational data in the SAPIEN 3 registry.23 In this cohort of 1077 intermediate risk patients (mean age 82 years, STS score 5.3%), TAVI was superior to a propensity-matched SAVR cohort, with a lower incidence of the composite of all-cause mortality, stroke and moderate or severe aortic regurgitation [pooled weighted proportion difference −9.2%, 95% confidence interval (CI) −13 to −5.4; P < 0.0001]. While PARTNER2A and SURTAVI found no difference in the headline primary outcome, there were important differences in the complication profiles of TAVI and SAVR. In PARTNER 2A, at 30 days TAVI was associated with a higher rate of major vascular complications (7.9% vs. 5.0%), but lower rates of new AF (9.1% vs. 26.4%) and life-threatening bleeding (10.4% vs. 43.4%) (all P < 0.01). In the trial, this included fatal bleeding, bleeding into a critical organ, bleeding causing hypovolaemic shock, or severe hypotension (requiring vasopressors or surgery), an overt source of bleeding with a drop in haemoglobin of ≥5 g/dL, or a transfusion of ≥4 units of blood or packed red cells. In SURTAVI, TAVI was also associated with higher rates of major vascular complication (6.0 vs. 1.1%), as well as residual moderate or severe PVL (5.3% vs. 0.6%), and pacemaker implantation (25.9% vs. 6.6%), but lower rates of acute kidney injury (1.7% vs. 4.4%) (differences outside 95% credible interval). The next frontier is patients at low surgical risk (STS < 4%), who account for 80% of patients undergoing SAVR. There are already early data in this group from the NOTION study, a small all-comers trial of 280 patients randomized to the CoreValve or SAVR.24 80% of patients had a mean STS score <4%, with a mean STS score in the TAVI arm of 2.9%. No difference was identified in the primary composite endpoint [all-cause mortality, stroke, or myocardial infarction (MI)] at 1 year (13.1% TAVI vs. 16.3% SAVR, −3.2% absolute difference, P = 0.43), although the study may have been underpowered. Transcatheter aortic valve implantation in low risk populations is being definitively addressed in three ongoing RCTs: PARTNER 3 (NCT02675114), Medtronic Evolut Low Risk (LR) (NCT02701283), and NOTION-2 (NCT02825134) (Figure 2). Notably, NOTION-2 is only enrolling patients <75 years and is therefore likely to report outcomes in the youngest TAVI population so far. Figure 2 View largeDownload slide Key ongoing randomized clinical trials in transcatheter aortic valve implantation (blue, Edwards Sapien 3; red, Medtronic Evolut R; green, any transcatheter valve), which will (A) expand the evidence base to patients with severe aortic stenosis at low surgical risk, (B) evaluate transcatheter aortic valve implantation for expanded indications, (C) define the optimal peri-procedural antithrombotic regime, and (D) clarify the role of cerebral protection devices. See text for specific details—timescales shown are estimated dates to primary endpoint completion (as shown on clinicaltrials.gov). Figure 2 View largeDownload slide Key ongoing randomized clinical trials in transcatheter aortic valve implantation (blue, Edwards Sapien 3; red, Medtronic Evolut R; green, any transcatheter valve), which will (A) expand the evidence base to patients with severe aortic stenosis at low surgical risk, (B) evaluate transcatheter aortic valve implantation for expanded indications, (C) define the optimal peri-procedural antithrombotic regime, and (D) clarify the role of cerebral protection devices. See text for specific details—timescales shown are estimated dates to primary endpoint completion (as shown on clinicaltrials.gov). Expanding indications for transcatheter aortic valve implantation As the incidence of complications associated with TAVI falls below that of SAVR, a debate is opening as to whether the classical indications for aortic valve replacement still stand. Transcatheter aortic valve implantation potentially provides an opportunity to intervene safely earlier in the natural history of AS using a minimally invasive technique that is highly acceptable to patients. However, given that long-term valve durability remains to be established, and redo valve procedures and coronary interventions following TAVI may be more challenging, its expanded use in younger populations must be supported by high quality clinical evidence. Trials are ongoing in two specific groups: those with moderate AS and impaired ventricular function, and asymptomatic patients with severe AS. Moderate aortic stenosis with impaired ventricular function Impaired left ventricular function is reported in up to a third of patients over 85 years of age, and commonly co-exists with AS.25 Outcomes in heart failure are improved by reduction in afterload, which improves cardiac output and organ perfusion. Aortic valve replacement reduces afterload in patients with severe aortic valve disease and left ventricular impairment to improve symptoms, contractile function, and survival.26 Patients with moderate AS and left ventricular dysfunction are at high risk of adverse outcome, with heart failure hospitalization or death occurring in 48% of patients at 4 years of follow-up in a recent series.27 It is unknown, however, whether valve replacement in patients with impaired ventricular function and co-existent moderate AS improves outcome. The ongoing TAVR UNLOAD trial (NCT02661451; Figure 2) will address precisely this question in patients with symptomatic heart failure, impaired left ventricular function (ejection fraction <50%, but >20%), and moderate AS [mean gradient (MG) ≥20 mmHg and <40 mmHg, and aortic valve area (AVA) 1.0–1.5 cm2 at rest]28 who will be randomized to transfemoral TAVI using the Sapien 3 valve or optimal heart failure therapy only. The primary endpoint is the hierarchical occurrence of all-cause death, disabling stroke, hospitalization for heart failure, symptomatic aortic valve disease, non-disabling stroke, and change in quality of life measures at 1 year. Asymptomatic severe aortic stenosis In asymptomatic AS, the upfront risks of SAVR have conventionally been thought to outweigh the benefits of intervention, leading to a strategy of active surveillance until symptoms or left ventricular impairment emerge.29 This approach has several problems. It is not always straightforward to determine whether symptoms are present, or whether AS is definitively responsible. The rate of progression of AS is variable, and despite surveillance ∼1% of asymptomatic patients die suddenly each year.30,31 In others, fibrosis or irreversible decline in cardiac function develop by the time of SAVR, leading to increased procedural risk and ongoing left ventricular dysfunction. While exercise treadmill testing or stress echocardiography can assist with risk stratification, even in those with a negative stress test (‘truly asymptomatic’), there is variable progression and an ongoing risk of sudden death.32,33 The development of TAVI as a less invasive lower risk procedure for aortic valve replacement may alter the risk-benefit balance of early intervention for patients with asymptomatic severe AS—a hypothesis currently being tested in the Early TAVR trial (NCT03042104; Figure 2). This study will randomize 1109 asymptomatic patients ≥65 years with severe AS (peak velocity ≥4m/s or MG ≥40 mmHg, AVA ≤1.0cm2 or AVA index ≤0.6) and a negative treadmill stress test to TAVI with the Edwards Sapien 3 valve or routine clinical surveillance. Primary endpoint data (composite of all-cause death, all stroke, and unplanned cardiovascular hospitalization) should be complete in December 2021. In parallel, there are evolving approaches to identify specific higher risk patient subsets who will benefit from early valve replacement. The ongoing EvoLVeD trial (NCT03094143) is currently assessing the significance of mid-wall fibrosis on cardiac magnetic resonance imaging (MRI)—patients with asymptomatic severe AS and mid-wall fibrosis are being randomized to valve replacement (by TAVI or SAVR) or routine care, with a primary endpoint of all-cause mortality or unplanned AS-related hospitalization. Current and future devices Clinical experience with TAVI is dominated by the Edwards Sapien and Medtronic CoreValve systems, but several newer valves are competing in expanding markets on design, repositionability and retrievability, and price. Improved valve sizing and design, and smaller delivery catheters have significantly reduced PVL and post-procedural complications, and this trend is likely to continue with future iterations.34 A comparison between the main valve systems is shown in Table 2. Many valves now incorporate sealing systems to reduce paravalvular aortic regurgitation—exemplified by an outer skirt on the Sapien 3 and a pericardial wrap on the Evolut PRO. The Acurate valve (Boston Scientific, previously Symetis) is a self-expanding supra-annular valve with a low rate of permanent pacemaker (PPM) implantation.35 The Portico valve (Abbott) is a self-expanding, fully resheathable and retrievable valve with leaflet geometry designed to function in both round and elliptical configurations. The repositionable and retrievable Lotus Valve is deployed using controlled mechanical expansion but has been recalled worldwide due to problems with its release mechanism.36 The JenaValve (JenaValve Technology, Germany) and J-valve (JieCheng Medical, China) have active fixation mechanisms that anchor the prosthesis to the valve leaflets, providing stability in the context of aortic regurgitation. The JenaValve is currently the only transcatheter valve with a Conformité Européene (CE) mark for use in patients with aortic regurgitation. Two further valves from China, the Venus-A® valve (Venus Medtech) and VitaFlow® (Microport), are at an advanced stage of development with high rates of procedural success in the challenging cohort of patients with bicuspid aortic valve (BAV) disease.37 Table 2 Comparative overview of selected transcatheter aortic valve systems   Acurate (Boston Scientific)  Allegra (NVT)  Centera (Edwards)  Evolut PRO (Medtronic)  Evolut R (Medtronic)  JenaValve (JenaValve)  Portico (St Jude)  Sapien 3 (Edwards)  VenusA (Venus Medtech)                      Design (leaflets, frame and delivery)  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Cobalt-chromium Balloon-expandble  Porcine pericardium Nitinol Self-expanding  Delivery routes and sheath size  TF, TA, TS 18 Fr/19 Fr  TF 18 Fr  TF, TS 14 Fr  TF, TAo, TS 16 Fr  TF, TAo, TS 14 Fr  TF, TA 18 Fr  TF, TA 18 Fr/19 Fr  TF, TA, TAo 14 Fr/16 Fr  TF, TA, TS 18 Fr/20 Fr  CE mark (years)  2011  2017  Awaited  2017  2013  2011 (AS) 2013 (AR)  2012  2014  NA  Specific advantages  Low PPM requirement  Resheathable up to 70% of deployment  Resheathable up to 85% deployment. PTFE skirt to reduce PVL. Motorized delivery system  Resheathable up to 80% deployment Double layer porcine pericardial skirt  Resheathable up to 80% deployment. Upcoming RCT data in low risk population  Active fixation for use in AR  Resheathable up to 85% deployment  External skirt to reduce PVL. Upcoming RCT data in low risk population  Experience in bicuspid valve population in China; reduced cost    Acurate (Boston Scientific)  Allegra (NVT)  Centera (Edwards)  Evolut PRO (Medtronic)  Evolut R (Medtronic)  JenaValve (JenaValve)  Portico (St Jude)  Sapien 3 (Edwards)  VenusA (Venus Medtech)                      Design (leaflets, frame and delivery)  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Cobalt-chromium Balloon-expandble  Porcine pericardium Nitinol Self-expanding  Delivery routes and sheath size  TF, TA, TS 18 Fr/19 Fr  TF 18 Fr  TF, TS 14 Fr  TF, TAo, TS 16 Fr  TF, TAo, TS 14 Fr  TF, TA 18 Fr  TF, TA 18 Fr/19 Fr  TF, TA, TAo 14 Fr/16 Fr  TF, TA, TS 18 Fr/20 Fr  CE mark (years)  2011  2017  Awaited  2017  2013  2011 (AS) 2013 (AR)  2012  2014  NA  Specific advantages  Low PPM requirement  Resheathable up to 70% of deployment  Resheathable up to 85% deployment. PTFE skirt to reduce PVL. Motorized delivery system  Resheathable up to 80% deployment Double layer porcine pericardial skirt  Resheathable up to 80% deployment. Upcoming RCT data in low risk population  Active fixation for use in AR  Resheathable up to 85% deployment  External skirt to reduce PVL. Upcoming RCT data in low risk population  Experience in bicuspid valve population in China; reduced cost  AR, aortic regurgitation; AS, aortic stenosis; PPM, permanent pacemaker; PVL, paravalvular leak; TA, transapical; TAo, transaortic; TF, transfemoral; TS, trans-subclavian. Table 2 Comparative overview of selected transcatheter aortic valve systems   Acurate (Boston Scientific)  Allegra (NVT)  Centera (Edwards)  Evolut PRO (Medtronic)  Evolut R (Medtronic)  JenaValve (JenaValve)  Portico (St Jude)  Sapien 3 (Edwards)  VenusA (Venus Medtech)                      Design (leaflets, frame and delivery)  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Cobalt-chromium Balloon-expandble  Porcine pericardium Nitinol Self-expanding  Delivery routes and sheath size  TF, TA, TS 18 Fr/19 Fr  TF 18 Fr  TF, TS 14 Fr  TF, TAo, TS 16 Fr  TF, TAo, TS 14 Fr  TF, TA 18 Fr  TF, TA 18 Fr/19 Fr  TF, TA, TAo 14 Fr/16 Fr  TF, TA, TS 18 Fr/20 Fr  CE mark (years)  2011  2017  Awaited  2017  2013  2011 (AS) 2013 (AR)  2012  2014  NA  Specific advantages  Low PPM requirement  Resheathable up to 70% of deployment  Resheathable up to 85% deployment. PTFE skirt to reduce PVL. Motorized delivery system  Resheathable up to 80% deployment Double layer porcine pericardial skirt  Resheathable up to 80% deployment. Upcoming RCT data in low risk population  Active fixation for use in AR  Resheathable up to 85% deployment  External skirt to reduce PVL. Upcoming RCT data in low risk population  Experience in bicuspid valve population in China; reduced cost    Acurate (Boston Scientific)  Allegra (NVT)  Centera (Edwards)  Evolut PRO (Medtronic)  Evolut R (Medtronic)  JenaValve (JenaValve)  Portico (St Jude)  Sapien 3 (Edwards)  VenusA (Venus Medtech)                      Design (leaflets, frame and delivery)  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Porcine pericardium Nitinol Self-expanding  Bovine pericardium Nitinol Self-expanding  Bovine pericardium Cobalt-chromium Balloon-expandble  Porcine pericardium Nitinol Self-expanding  Delivery routes and sheath size  TF, TA, TS 18 Fr/19 Fr  TF 18 Fr  TF, TS 14 Fr  TF, TAo, TS 16 Fr  TF, TAo, TS 14 Fr  TF, TA 18 Fr  TF, TA 18 Fr/19 Fr  TF, TA, TAo 14 Fr/16 Fr  TF, TA, TS 18 Fr/20 Fr  CE mark (years)  2011  2017  Awaited  2017  2013  2011 (AS) 2013 (AR)  2012  2014  NA  Specific advantages  Low PPM requirement  Resheathable up to 70% of deployment  Resheathable up to 85% deployment. PTFE skirt to reduce PVL. Motorized delivery system  Resheathable up to 80% deployment Double layer porcine pericardial skirt  Resheathable up to 80% deployment. Upcoming RCT data in low risk population  Active fixation for use in AR  Resheathable up to 85% deployment  External skirt to reduce PVL. Upcoming RCT data in low risk population  Experience in bicuspid valve population in China; reduced cost  AR, aortic regurgitation; AS, aortic stenosis; PPM, permanent pacemaker; PVL, paravalvular leak; TA, transapical; TAo, transaortic; TF, transfemoral; TS, trans-subclavian. There are few studies allowing direct comparison between current valve systems. The CHOICE study randomized patients to the Sapien XT or CoreValve, demonstrating similar mortality but a higher risk of PVL (>mild) with CoreValve.38 Both valves have now been superseded by newer versions, however, and a contemporary RCT of the S3 and Evolut R has not been conducted. The REPRISE III trial compared the mechanically-expanded Lotus Valve and the CoreValve, demonstrating non-inferiority of the Lotus Valve in terms of safety and a significant reduction in moderate and severe PVL (0.9% vs. 6.8%, P < 0.01), at the cost of higher pacemaker requirement (35.5% vs. 19.6%, P < 0.001).39 Meanwhile, the ongoing SCOPE I and SCOPE II studies will provide similar comparisons of the Acurate valve with the S3 and Evolut CoreValve systems, respectively. Further investigator-led studies into the range of new valve systems will be valuable to compare efficacy, durability and complication profiles. Ongoing challenges Despite the indisputable success of TAVI, there are numerous remaining challenges. It is important to look beyond early technical success and short-medium term safety, which have been the focus of most studies to date. A recent European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) statement, the internationally agreed VARC-2 endpoints, and a recent consensus document from the VIVIV group provide important standardization for trials focusing on long-term durability and late complications.40–42 Ultimately, the aim should be to not only match SAVR but also set a new gold standard for patients undergoing valve intervention. Valve durability and function Structural valve deterioration (SVD) is defined by permanent intrinsic changes of the valve (calcification, pannus, and leaflet failure) leading to degeneration and/or dysfunction, which in turn may result in valvular stenosis or intra-prosthetic regurgitation.41 The risk of SVD is heavily influenced by valve design and patient age at the time of implantation. Durable long-term outcomes have been reported for surgical bioprosthetic valves, but freedom from SVD at 15 years ranges from 67% in patients aged <60 years to 92% in patients >70 years.43,44 Valve design may influence SVD unpredictably—notable examples of early valve failure due to intrinsic design problems are the Ionescu-Shiley pericardial tissue valve and the St. Jude Toronto SPV valve.45 Concerns that transcatheter valves might suffer from early SVD have not so far materialized, with 5 years outcomes from PARTNER I showing that SVD requiring intervention is rare (∼0.2%).46 Moderate or severe transvalvular regurgitation developed in 3.7% after TAVI, increasing over time. In a multicentre registry study of 1521, TAVI patients over mean echocardiographic follow-up of 20 ± 13 months, 4.5% of patients developed an increase in mean transvalvular gradient of ≥10 mmHg, with a mean increase of 0.30 ± 4.99 mmHg/year.47 Independent predictors of a rising gradient were absence of anticoagulation, a valve-in-valve procedure, use of a 23 mm valve and greater body mass index. While this medium term follow-up is reassuring, studies of surgical bioprostheses indicate that SVD before 10 years is rare, and continued close follow-up is essential to establish the long-term durability of transcatheter valves. By the early 2020s, data will be available for a relatively small number of patients who received first generation valves. Establishing durability in large cohorts and determining the relative freedom from SVD of different valve designs will take longer but is of crucial importance as TAVI moves into lower age groups. In addition, development of transcatheter strategies for treatment of degenerated TAVI valves (i.e. redo-TAVI) is a current research and engineering priority. Although SVD appears rare, there may be a signal of concern regarding subclinical leaflet thrombosis.48 Identified on CT imaging in 10–15% of TAVI patients, this phenomenon that manifests as leaflet thickening and reduced leaflet motion has been correlated with thrombus. Although risk factors for subclinical leaflet thrombosis are not clearly identified, regional stent frame under-expansion has been associated with an increased risk of leaflet thickening, while post-dilatation of self-expanding valves and a supra-annular valve position seem to reduce its frequency.49 Furthermore, oral anticoagulant (OAC) therapy (but not dual antiplatelet therapy, DAPT) seems to prevent and resolve the phenomenon.39 Recent analysis of 931 patients in the combined RESOLVE-SAVORY registries demonstrates that valve dysfunction (aortic valve gradient >20 mmHg) remains uncommon but occurs more frequently in patients with valve thrombosis (14% vs. 1%, P < 0.0001).50 Even though leaflet thrombosis was associated with an increased risk of transient ischaemic attack (4.18 vs. 0.6 per 100 person years, P = 0.0005), these findings must be interpreted with caution due to temporal separation between the CT and the clinical event. Ongoing studies of different regimes of OAC or anti-platelet therapy following TAVI are keenly awaited and long-term OAC may prove necessary for some patients. Stroke Stroke is a devastating complication of TAVI and associated with a 5–10 fold increased risk of short-term mortality.51,52 Patients undergoing TAVI are at increased risk of embolic stroke during the procedure (associated primarily with valve positioning and deployment) and during a post-procedural phase lasting weeks to months.53 The risk of stroke in PARTNER I was over twice as high in the TAVI cohort compared with SAVR (5.5% vs. 2.4% at 30 days, P = 0.04), although this difference diminished over time and has not been observed in subsequent trials. The incidence of stroke 30 days following TAVI was 3.1% in PARTNER IIA and significantly lower than after SAVR in SURTAVI (3.3% TAVI vs. 5.4% SAVR, P = 0.031). Large scale data from the TVT registry report a rate of clinically significant stroke of 2.5% at 30 days and 4.1% at 1 year.54 Strategies to reduce stroke have focused on embolic protection and anticoagulation. Following TAVI up to 75% of patients have new ischaemic lesions on diffusion-weighted cerebral MRI, making embolic protection intuitively attractive.55 The CLEAN-TAVI trial randomized 100 patients undergoing TAVI to the Montage filter or control, and demonstrated a reduction in the primary endpoint of cerebral infarct volume.56 In contrast, the SENTINEL trial (Sentinel device, Claret Medical) found a trend towards reduced infarct volume (that did not reach statistical significance) and no difference in the rate of clinical stroke.57 A recent observational series has reported stroke reduction with the Sentinel device (4.6–1.4%, P = 0.03), but this requires further validation.58 Several trials are ongoing, including PROTECT-TAVI (Sentinel) and REFLECT (TriGuard) (Figure 2). Although new imaging lesions have been linked to deterioration in neurocognitive status, they do not represent stroke, and the clinical benefits of embolic protection remain to be clearly established. The role of antiplatelet and OAC agents to prevent stroke following TAVI is currently ill-defined, but the evidence base is evolving rapidly. Coronary disease, recent percutaneous intervention, and AF are common in the TAVI population, and between 10% and 30% of patients have new-onset AF following TAVI leading to increased risk of stroke.59,60 Although DAPT is routinely used post-TAVI, this is not supported by strong evidence. The recent ARTE trial compared DAPT with aspirin monotherapy post-TAVI in 222 patients and demonstrated that the composite of death, MI, stroke or transient ischaemic attack, or major or life-threatening bleeding tended to occur less frequently in the aspirin group (7.2% vs. 15.3%, P = 0.065), and that aspirin alone led to a reduction in major or life-threatening bleeding (3.6% vs. 10.8%, P = 0.038).61 Three further upcoming trials will inform the use of OAC following TAVI (Figure 2). The GALILEO RCT (NCT02556203) is comparing Rivaroxaban plus Aspirin with DAPT (Aspirin and Clopidogrel). The ATLANTIS study (NCT02664649) is randomising patients with an indication for OAC to a vitamin K antagonist or Apixaban, and those without to either DAPT, a single antiplatelet agent or Apixaban. Finally, the POPULAR-TAVI trial (NCT02247128) is investigating the additional role of Clopidogrel to OAC in patients who require anticoagulation, and the merits of DAPT against aspirin monotherapy in those without an indication for anticoagulation. Permanent pacemaker implantation Interference with the cardiac conduction system is common after TAVI, with new left bundle branch block (LBBB) or complete atrioventricular block necessitating PPM implantation in ∼5–35% of patients.62,63 The impact of new conduction disease is controversial: PARTNER I identified an increased incidence of mortality/repeat hospitalization at 1 year in patients requiring a PPM (42 vs. 32.6%, P = 0.007), with a similar increase in mortality associated with PPM implantation in the TVT registry (24.1% vs. 19.6%, hazard ratio 1.31; 95% CI 1.09–1.58).63,64 Although this adverse effect has not been observed in other studies, the consequences of long-term right ventricular pacing are well-documented and preferably avoided, especially in younger patients with longer life-expectancy.65,66 Patient, procedure and device-related risk factors have been identified. Those at increased risk of conduction disturbance include older, male patients, and those with pre-existing conduction disease (especially right bundle branch block), a small outflow tract, or calcification of the aortic or mitral valve annulus.67 Procedural risk factors include valve oversizing, deep implantation, and balloon post-dilatation. Valve design also has a major impact—the CoreValve and Lotus valve have the highest rates of PPM requirement (30–40% for the latter),68,69 whereas the Acurate NEO (Boston Scientific, previously Symetis) is associated with PPM rates as low as 2.3% (10.3% new LBBB). Further work is required to optimize valve design, implantation technique and device selection to reduce PPM requirements while ensuring minimal incidence of PVL. Vascular access Transfemoral TAVI now dominates as the safest and simplest vascular access route, and is associated with improved outcomes compared with other approaches. Facilitated by smaller delivery systems and expandable sheath or sheath-less approach, transfemoral valve delivery is achievable in at least 90% of cases, and the incidence of major vascular complications has reduced to ∼2% in contemporary practice. However, transfemoral access is not viable for a small minority of patients and alternative routes are required. Multiple possible strategies have been reported, including subclavian/axillary, carotid, transapical, direct aortic, and transcaval access. Although not all routes have been directly compared, retrospective data suggest that subclavian access is the safest choice for non-femoral access, with outcomes similar to the transfemoral approach.70 In future, direct aortic access via the inferior vena cava (transcaval approach) may be preferred, with recent series demonstrating feasibility in 99% of cases (n = 100), albeit with reported rates of retroperitoneal or life-threatening bleeding of 24% and 7%, respectively.71 Bicuspid aortic valve Bicuspid aortic valve anatomy is found in 0.5–2.0% of the population, and AS affecting a bicuspid valve is the most common indication for SAVR in patients <70 years of age. Bicuspid AS is associated with specific anatomic challenges relevant to TAVI; heavy valve calcification, an eccentrically shaped annulus, and a horizontal, dilated aorta. While technically feasible, the number of patients with BAV who have undergone TAVI is small, and this group demonstrate significant rates of moderate to severe PVL (∼10%) and major vascular complications.72 Patients with BAV are at specific risk of aortic root complications due to heavy calcification or associated aortopathy. For these reasons, BAV has been an exclusion criteria in many TAVI trials. However, outcomes are improving with new devices: in the Bicuspid TAVR registry of 301 patients, moderate or severe PVL was less frequent with new devices (Sapien 3 or Lotus) compared with the CoreValve or Sapien XT (0.0% vs. 8.5%, P = 0.002).73 The same registry also reported no significant difference in clinical outcomes or rates of PVL between Type 0 (’pure’) and Type I (single raphe) anatomy, in contrast to earlier studies in which Type I BAV was a risk factor for PVL.72,74 Further reductions in the incidence of PVL and aortic root complications in patients with challenging anatomy are an important next step in the evolution of TAVI. Infective endocarditis Infective endocarditis affects approximately 0.5–3% of patients within the first year following TAVI and has an in-hospital mortality of 30–60%.75,76 Management is extremely challenging: many patients have been previously deemed unfit for cardiac surgery and the majority are therefore treated with antibiotic therapy alone.75,77 TAVI-related endocarditis is most commonly caused by Enterococcus species, which gain access to the circulation from the gastrointestinal or genitourinary tract. Given the difficulties of treatment, prevention is the logical focus. TAVI recipients may benefit from expanded use of antibiotic prophylaxis to cover gastrointestinal and genitourinary procedures, and this warrants further research. Rigorous sterility is of paramount importance, particularly when TAVI is conducted in the catheter laboratory environment, although procedural location has not been found to be a specific risk factor for the development of endocarditis.77 Valve design may also play a role—the Xeltis valve, a bioabsorbable polymer scaffold, which is endothelialized and eventually replaced by recipient tissue, is in pre-clinical development and may reduce risk of bacterial adherence and consequent endocarditis.78 Current clinical guidelines The central position of TAVI in the contemporary management of AS has been underwritten by the ESC/EACTS 2017 guidelines for the management of valvular heart disease (Figure 3; Table 3),2 which not only outline straightforward pointers in favour of TAVI or SAVR, but also afford considerable discretion to the treating Heart Team. Patients at low surgical risk (STS < 4%) with no specific features to favour TAVI (Table 3) should undergo SAVR. For all others, however, the choice between TAVI and SAVR should be based on the risk: benefit ratio for a given individual and their technical suitability for either procedure. Specific factors in favour of TAVI include the presence of severe comorbidity, age ≥75 years, previous cardiac surgery, frailty, restricted mobility, conditions likely to affect rehabilitation, and aortic anatomy permitting transfemoral delivery. Table 3 Considerations for the Heart Team in the choice between TAVI and surgical aortic valve replacement   Favours TAVI  Favours SAVR  Clinical characteristics   STS/EuroSCORE II <4%    +   STS/EuroSCORE II ≥4%  +     Presence of severe comorbidity not adequately reflected by scores  +     Age <75    +   Age ≥75  +     Previous cardiac surgery  +     Frailty  +     Restricted mobility and conditions that may affect rehabilitation  +     Suspicion of endocarditis    +  Anatomical and technical aspects   Favourable transfemoral access  +     Unfavourable access (any) for TAVI    +   Sequelae of chest radiation  +     Porcelain aorta  +     Presence of intact CABG at risk when sternotomy is performed  +     Expected patient-prosthesis mismatch  +     Severe chest deformation or scoliosis  +     Short distance between coronary ostia and aortic valve annulus    +   Size of aortic valve annulus out of range for TAVI    +   Aortic root morphology unfavourable for TAVI    +   Valve morphology (bicuspid, degree, or pattern of calcification) unfavourable for TAVI    +   Presence of thrombi in the aorta    +  Cardiac conditions where concomitant intervention should be considered   Severe CAD requiring revascularization by CABG    +   Severe primary mitral valve disease, which could be treated surgically    +   Severe tricuspid disease    +   Aneurysm of the ascending aorta    +   Septal hypertrophy requiring myectomy    +    Favours TAVI  Favours SAVR  Clinical characteristics   STS/EuroSCORE II <4%    +   STS/EuroSCORE II ≥4%  +     Presence of severe comorbidity not adequately reflected by scores  +     Age <75    +   Age ≥75  +     Previous cardiac surgery  +     Frailty  +     Restricted mobility and conditions that may affect rehabilitation  +     Suspicion of endocarditis    +  Anatomical and technical aspects   Favourable transfemoral access  +     Unfavourable access (any) for TAVI    +   Sequelae of chest radiation  +     Porcelain aorta  +     Presence of intact CABG at risk when sternotomy is performed  +     Expected patient-prosthesis mismatch  +     Severe chest deformation or scoliosis  +     Short distance between coronary ostia and aortic valve annulus    +   Size of aortic valve annulus out of range for TAVI    +   Aortic root morphology unfavourable for TAVI    +   Valve morphology (bicuspid, degree, or pattern of calcification) unfavourable for TAVI    +   Presence of thrombi in the aorta    +  Cardiac conditions where concomitant intervention should be considered   Severe CAD requiring revascularization by CABG    +   Severe primary mitral valve disease, which could be treated surgically    +   Severe tricuspid disease    +   Aneurysm of the ascending aorta    +   Septal hypertrophy requiring myectomy    +  Reproduced with permission from Baumgartner et al.2 CABG, coronary artery bypass grafting; CAD, coronary artery disease. Table 3 Considerations for the Heart Team in the choice between TAVI and surgical aortic valve replacement   Favours TAVI  Favours SAVR  Clinical characteristics   STS/EuroSCORE II <4%    +   STS/EuroSCORE II ≥4%  +     Presence of severe comorbidity not adequately reflected by scores  +     Age <75    +   Age ≥75  +     Previous cardiac surgery  +     Frailty  +     Restricted mobility and conditions that may affect rehabilitation  +     Suspicion of endocarditis    +  Anatomical and technical aspects   Favourable transfemoral access  +     Unfavourable access (any) for TAVI    +   Sequelae of chest radiation  +     Porcelain aorta  +     Presence of intact CABG at risk when sternotomy is performed  +     Expected patient-prosthesis mismatch  +     Severe chest deformation or scoliosis  +     Short distance between coronary ostia and aortic valve annulus    +   Size of aortic valve annulus out of range for TAVI    +   Aortic root morphology unfavourable for TAVI    +   Valve morphology (bicuspid, degree, or pattern of calcification) unfavourable for TAVI    +   Presence of thrombi in the aorta    +  Cardiac conditions where concomitant intervention should be considered   Severe CAD requiring revascularization by CABG    +   Severe primary mitral valve disease, which could be treated surgically    +   Severe tricuspid disease    +   Aneurysm of the ascending aorta    +   Septal hypertrophy requiring myectomy    +    Favours TAVI  Favours SAVR  Clinical characteristics   STS/EuroSCORE II <4%    +   STS/EuroSCORE II ≥4%  +     Presence of severe comorbidity not adequately reflected by scores  +     Age <75    +   Age ≥75  +     Previous cardiac surgery  +     Frailty  +     Restricted mobility and conditions that may affect rehabilitation  +     Suspicion of endocarditis    +  Anatomical and technical aspects   Favourable transfemoral access  +     Unfavourable access (any) for TAVI    +   Sequelae of chest radiation  +     Porcelain aorta  +     Presence of intact CABG at risk when sternotomy is performed  +     Expected patient-prosthesis mismatch  +     Severe chest deformation or scoliosis  +     Short distance between coronary ostia and aortic valve annulus    +   Size of aortic valve annulus out of range for TAVI    +   Aortic root morphology unfavourable for TAVI    +   Valve morphology (bicuspid, degree, or pattern of calcification) unfavourable for TAVI    +   Presence of thrombi in the aorta    +  Cardiac conditions where concomitant intervention should be considered   Severe CAD requiring revascularization by CABG    +   Severe primary mitral valve disease, which could be treated surgically    +   Severe tricuspid disease    +   Aneurysm of the ascending aorta    +   Septal hypertrophy requiring myectomy    +  Reproduced with permission from Baumgartner et al.2 CABG, coronary artery bypass grafting; CAD, coronary artery disease. Figure 3 View largeDownload slide European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines for the management of severe aortic stenosis. Surgical aortic valve replacement is indicated in asymptomatic patients if there is left ventricular systolic dysfunction due to aortic stenosis (ejection fraction <50%) (Class I, level of evidence C). Risk stratification by exercise testing can be performed in those with normal ejection fraction—surgical aortic valve replacement is indicated if symptoms develop (or blood pressure drops) during exercise. In those with a normal exercise test (or unable to exercise), evaluation of predictors of progression (peak velocity ≥5.5 m/s, severe valve calcification + increase in peak velocity >0.3 m/s/year, elevated neurohormonal levels, or severe pulmonary hypertension), and surgical risk should guide the choice between activate surveillance and surgical aortic valve replacement. In patients with symptomatic severe aortic stenosis, there is a Class I, level of evidence B recommendation for aortic valve intervention. Surgical aortic valve replacement is the default in those at low risk with no characteristics favouring transcatheter aortic valve implantation. Heart Team evaluation to assess suitability and risk-benefit ratio of transcatheter aortic valve implantation vs. surgical aortic valve replacement is appropriate in all other patients. Reproduced with permission from Baumgartner et al.2 AS, aortic stenosis; LVEF, left ventricular ejection fraction; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation. Figure 3 View largeDownload slide European Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines for the management of severe aortic stenosis. Surgical aortic valve replacement is indicated in asymptomatic patients if there is left ventricular systolic dysfunction due to aortic stenosis (ejection fraction <50%) (Class I, level of evidence C). Risk stratification by exercise testing can be performed in those with normal ejection fraction—surgical aortic valve replacement is indicated if symptoms develop (or blood pressure drops) during exercise. In those with a normal exercise test (or unable to exercise), evaluation of predictors of progression (peak velocity ≥5.5 m/s, severe valve calcification + increase in peak velocity >0.3 m/s/year, elevated neurohormonal levels, or severe pulmonary hypertension), and surgical risk should guide the choice between activate surveillance and surgical aortic valve replacement. In patients with symptomatic severe aortic stenosis, there is a Class I, level of evidence B recommendation for aortic valve intervention. Surgical aortic valve replacement is the default in those at low risk with no characteristics favouring transcatheter aortic valve implantation. Heart Team evaluation to assess suitability and risk-benefit ratio of transcatheter aortic valve implantation vs. surgical aortic valve replacement is appropriate in all other patients. Reproduced with permission from Baumgartner et al.2 AS, aortic stenosis; LVEF, left ventricular ejection fraction; SAVR, surgical aortic valve replacement; TAVI, transcatheter aortic valve implantation. The ESC/EACTS guidelines advocate centralized care, with a Class I recommendation that TAVI is performed in a Heart Valve Centre with on-site surgery.2 The role of the Heart Team is core, in practice comprising two interventional cardiologists, two cardiac surgeons, and a cardiac imaging specialist, as well as input from care of the elderly, anaesthetics, and nurse specialists.79 A full spectrum of imaging modalities should be available, and outcomes should be transparently reported and publicly available. These recommendations may prove controversial: some TAVI procedures in Germany are already being performed at non-surgical sites.80 However, a direct relationship between higher case volume and lower mortality has been demonstrated in the same country, with an in-hospital mortality of 5.2% (95% CI 4.8–5.7) in the highest volume quintile vs. 7.6% (7.1–8.2) in the lowest volume quintile.81,82 The minimum number of cases required to fall below average mortality (6.6%) was 157/year. These data support the centralized Heart Valve Centre model, with access to the full spectrum of surgical and transcatheter valve interventions on-site, as defined in current ESC guidelines.2 This model incorporates side-by-side decision-making with surgical colleagues, alongside audit of outcomes and training of a new generation of structural interventionists. Importantly, it will also promote a critical mass of expertise as percutaneous treatment options for mitral and tricuspid valve disease emerge. The future In the context of an expanding, ageing population, the number of TAVI procedures is set to grow 4–10-fold over the next decade.83,84 In many countries, the challenges of cost and infrastructural development are already the rate-limiting step to implementation of TAVI, rather than the clinical evidence base. Transfemoral delivery and a simplified procedure are increasing availability, but the maintenance of high quality decision-making, excellent outcomes and specialist training in a Heart Valve Centre are critical. Meeting the logistic challenge of delivering TAVI care will require a new cadre of structural interventionists, derived through cardiological, surgical, or hybrid training routes. The relative cost of devices will come under increasing scrutiny in a competing market of valves with broad clinical equivalence, and this will improve affordability and overall cost-effectiveness. In 2018, TAVI is already a refined, low-risk procedure for aortic valve replacement with evidence of intermediate durability. Within a few years, transfemoral TAVI is likely to demonstrate non-inferiority to SAVR in patients at low procedural risk, and may show benefit over active surveillance in the asymptomatic population. More challenging is the transition to younger patients: TAVI must demonstrate durability equivalent to surgical bioprostheses, and options will be required for dealing with SVD when it occurs. Ongoing valve innovation is necessary, in particular to achieve comparable outcomes for challenging anatomy (particularly BAV). Specific patient subsets are likely to benefit from different antiplatelet and OAC combinations, and these remain to be defined. Reducing the requirement for PPM implantation while ensuring minimal incidence of PVL is a further important requirement before TAVI can be widely used in younger patients. These challenges are not insurmountable. TAVI has deftly navigated infancy and adolescence: as it comes of age its future looks extremely bright. Conflict of interest: K.H. is a clinical proctor for Edwards Lifesciences. A.L. is a consultant for Medtronic and Abbott Vascular and has received unrestricted research grants from Edwards Lifesciences and Medtronic. 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European Heart JournalOxford University Press

Published: Apr 27, 2018

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