**Abstract**

Severe calcific aortic stenosis (AS) is commonly seen in the elderly population, and as human longevity increases, the prevalence of severe AS is bound to increase. Symptomatic severe AS, if left untreated, carries high mortality with 2-year survival below 50%. Surgical aortic valve replacement (SAVR) had been the standard of care for such patients with excellent outcome. As the patient's comorbidities increase, so does surgical risk for SAVR. Since its first human use in 2002 and commercial approval in 2007 (CE mark, Europe), transcatheter aortic valve replacement (TAVR) has come up as an excellent alternative to SAVR in patients with higher surgical risk profile. Iterations in device design added to enhanced operator experience can be attributed towards improved clinical outcomes. Indications for TAVR continues to expand and now includes patients with intermediate surgical risk as well. This chapter discusses indications and evidence for TAVR and touches upon patient selection and complications after TAVR.

**Keywords:** severe aortic stenosis, transcatheter aortic valve replacement, indications of TAVR, complications of TAVR, trials on TAVR

#### **1. Introduction**

A population-based study done by Eveborn et al. demonstrated an increase in the prevalence of AS with age, from 0.2% at 50–59 years to 9.8% at 80–89 years [1].

Prevalence of any AS and severe AS from pooled data involving multiple studies was shown to be 12.5 and 3.4% respectively among people of age >75. Approximately half to one-third of patients with severe AS may be asymptomatic at the time of diagnosis [2].

Due to long asymptomatic period associated with severe Aortic stenosis, patients may not report any overt symptoms, or compensate for their decreased exertional capacity by slowing down their daily activities attributing it to normal aging. Addressing symptom onset in patients with severe AS is extremely important as the onset of symptoms markedly decreases survival unless aortic valve replacement is performed.

Early observation done by Ross and Braunwald [3] showed that patients with angina have a 50% 5-year survival rate without AVR, those with syncope have 50% 3-year survival. Heart failure carries worse prognosis with mean survival rate of less than 2 years without AVR.

#### **Table 1.**

*Indications for balloon aortic valvuloplasty (BAV).*

While SAVR is considered standard of care for management of symptomatic severe aortic stenosis, one-third of patients with severe AS with indications for SAVR may be denied surgery in view of advanced age and comorbidities.

Catheter-based balloon aortic valvuloplasty (BAV) was developed in 1985 as a less invasive solution for patients with symptomatic severe AS who were denied SAVR.

High rates of recurrence (80%) at 1 year associated with BAV hindered its widespread adaptability and search for other less invasive therapeutic option for severe AS patients was continued.

Contemporary indications for BAV are listed in **Table 1**. Currently, BAV is reserved for use as a bridge-to-decision to provide more definitive therapy for AS and for patients with contraindications for TAVR in whom relief of Aortic obstruction will improve quality of life.

#### **2. TAVR: early concepts**

To circumvent restenosis after BAV, a combination of stent frame and valve within was thought as an alternative. This arrangement could potentially implant an aortic valve in place of diseased native aortic valve using minimally invasive catheterization technique, thus avoiding high morbidity and mortality associated with high risk SAVR. Routine observation of high-pressure balloon inflation (4–5 atmospheres) leading to opening of all calcified aortic valves in a circular fashion led to the concept of TAVR [4].

In 1992, Andersen and colleagues [5], used a hand-made porcine valve contained within a metallic mesh and successfully implanted at various cardiac sites in a pig model. This was the first evidence of use of a stented valve.

In 1999 percutaneous valve technologies (PVT) designed early models of balloon expandable transcatheter heart valve (THV) [4].

The first human implantation of a percutaneous stented valve to a degenerated right ventricle-to-pulmonary artery conduit was done in 2000 by Bonhoeffer and colleagues [6]. This was a bovine jugular valve mounted on stent platform.

After initial success with the sheep model, Dr. Alain Cribier and his team performed the first successful TAVR in human using a balloon expandable THV on 16th April 2002 as a bailout procedure after failed emergency BAV [4].

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*Transcatheter Aortic Valve Replacement: Clinical Indications and Outcomes*

**3. Evolution of TAVR: indications and clinical trial evidence for TAVR**

After initial success with the Sheep model, first human implantation with the balloon expandable Edwards valve was done on 16th April 2002 after failed emer-

After encouraging initial results, Dr. Cribier and team were able to recapitulate TAVR in a few patients. Worldwide demonstrations of this innovative therapy led to its increased acceptance. TAVR was transforming from a crazy idea to a viable therapy option. The Cribier valve technology was acquired by Edwards Lifesciences (Irvine, CA) for further development, and the THV was further marketed as

Simultaneously scientists from Europe were working on a self-expandable valve (CoreValve, Medtronic, Inc.; Minneapolis, MN) platform as an alternative to balloon expandable valve since 2004 and human implantations were being done

As the number of TAVR implantations increased, data from multiple small studies and registries like SOURCE, ADVANCE, FRANCE I and FRANCE II showed

With the available data, the European CE mark authorization was granted in August 2007 for the Edwards Sapien balloon expandable THV with the transfemoral RetroFlex delivery system and in January 2008 for use with the transapical

PARTNER was the first randomized trial that compared TAVR with standard therapy. Cohort B of this landmark trial demonstrated superiority of TAVR over medical therapy in patients with severe symptomatic AS who were considered extreme (or prohibitive) risk for SAVR. At 1 year follow up, absolute risk reduction in all-cause mortality of 20% was observed, a finding which held true even at

Cohort A of PARTNER trial compared TAVR with SAVR and showed that TAVR was non-inferior to SAVR in patients with high surgical risk (society of thoracic surgeons (STS) score >8%). CoreValve extreme risk trial data showed benefit of

With the available evidence from randomised control trials (RCTs) and multiple

Intermediate surgical risk (STS score ≥4–8%) patients with symptomatic severe AS were enrolled in PARTNER 2 trial comparing TAVR using second generation Sapien valve (Sapien XT) with SAVR along with subgroup analysis of transfemoral and transthoracic cohorts. All-cause mortality in TAVR arm was non-inferior to SAVR at 2 years with comparable stroke and permanent pacemaker rates.

The SURTAVI (surgical replacement and transcatheter aortic valve implantation) trial used Self-expandable CoreValve and enrolled patients with symptomatic severe AS with intermediate surgical risk and showed all-cause mortality in TAVR

registry data, TAVR was given Class I LOE B recommendation in patients with prohibitive (not suitable for SAVR) and increased surgical risk by ESC guidelines

Another important observation noted in PARTNER 1 trial was diminishing survival benefit of TAVR with higher STS score. This led to stress more importance

In November 2011, United States Food and Drug Administration (US FDA) approved TAVR as a treatment option for patients with symptomatic severe AS who were considered inoperable for SAVR. Favourable clinical data using self-expanding THV CoreValve (Medtronic) led to its USFDA approval in 2014 on similar patient

procedural success (30 days survival) ranging from 67–92%.

*DOI: http://dx.doi.org/10.5772/intechopen.84909*

gency BAV as a bailout procedure [4].

Edwards Sapien valve.

Ascendra delivery device.

5 years follow up [7].

on patient selection.

subset.

TAVR with reduction in all-cause mortality.

[8] and Class I LOE A by ACC/AHA guidelines [9].

group non-inferior to SAVR at 1 and 2 years.

successfully.

*Aortic Stenosis - Current Perspectives*

While SAVR is considered standard of care for management of symptomatic severe aortic stenosis, one-third of patients with severe AS with indications for SAVR may be denied surgery in view of advanced age and comorbidities.

Catheter-based balloon aortic valvuloplasty (BAV) was developed in 1985 as a less invasive solution for patients with symptomatic severe AS who were denied

High rates of recurrence (80%) at 1 year associated with BAV hindered its widespread adaptability and search for other less invasive therapeutic option for severe

Contemporary indications for BAV are listed in **Table 1**. Currently, BAV is reserved for use as a bridge-to-decision to provide more definitive therapy for AS and for patients with contraindications for TAVR in whom relief of Aortic obstruc-

To circumvent restenosis after BAV, a combination of stent frame and valve within was thought as an alternative. This arrangement could potentially implant an aortic valve in place of diseased native aortic valve using minimally invasive catheterization technique, thus avoiding high morbidity and mortality associated with high risk SAVR. Routine observation of high-pressure balloon inflation (4–5 atmospheres) leading to opening of all calcified aortic valves in a circular fashion led to

In 1992, Andersen and colleagues [5], used a hand-made porcine valve contained within a metallic mesh and successfully implanted at various cardiac sites in a pig

In 1999 percutaneous valve technologies (PVT) designed early models of bal-

The first human implantation of a percutaneous stented valve to a degenerated right ventricle-to-pulmonary artery conduit was done in 2000 by Bonhoeffer and

colleagues [6]. This was a bovine jugular valve mounted on stent platform. After initial success with the sheep model, Dr. Alain Cribier and his team performed the first successful TAVR in human using a balloon expandable THV on

16th April 2002 as a bailout procedure after failed emergency BAV [4].

model. This was the first evidence of use of a stented valve.

loon expandable transcatheter heart valve (THV) [4].

**50**

SAVR.

**Table 1.**

AS patients was continued.

tion will improve quality of life.

*Indications for balloon aortic valvuloplasty (BAV).*

**2. TAVR: early concepts**

the concept of TAVR [4].
