**7. Intermediate risk patients: who are they? And how do we have to manage them?**

As we described before, currently AHA/ACC guideline for the management of patients with valvular heart disease [7, 19] defines the intermediate-risk patients as those who has an **STS 4**–**8%** with no more than mild frailty or one major organ system compromise not to be improved postoperatively and minimal procedurespecific impediments. In the other hand, the European guidelines define such patient as at "increased surgical risk" (STS or EuroSCORE II >4% or logistic EuroSCORE I > 10% or other risk factors not included in these scores such as frailty, porcelain aorta, and sequelae of chest radiation) [8].

### *This cohort of patients has two therapeutic options, surgical AVR or TAVI, and the decision pathway goes through the accurate interpretation of all data by the Heart Team.*

Nowadays, increased operator experience and enhanced transcatheter valve systems have led to a worldwide trend to use TAVI in patients who are at low or intermediate risk [45]. This tendency has been evaluated in small observational studies, but since most patients who are currently recommended for surgery are at low or intermediate risk, the expansion of the use of TAVI demands more rigorous clinicaltrial validation [46]. The intermediate-surgical-risk trials were approved comparing TAVI to surgery, with the balloon-expandable SAPIEN XT valve (PARTNER 2 trial) and the self-expandable CoreValve (SUrgical Replacement and Transcatheter Aortic Valve Implantation trial (SURTAVI trial)) [46, 47].

**The PARTNER 2** trial [46] was a multicenter, randomized control trial conducted, which enrolled 2032 patients with severe symptomatic aortic stenosis and intermediate-surgical-risk, and randomized them in a 1:1 fashion across the TAVI arm and the surgical arm [48]. After 2 years, the all-cause mortality or disabling stroke was similar in the TAVI group and the SAVR group (19.3 vs. 21.1%, p = 0.33 and p = 0.001 for **noninferiority**). In the transfemoral access cohort, TAVI demonstrated a lower mortality and disabling stroke (hazard ratio = 0.79; 95% CI = 0.62–1.00; p = 0.05). TAVI resulted in larger aortic valve areas, lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; SAVR resulted in fewer major vascular complications and less paravalvular aortic leak [49]. As a result of the PARTNER 2 trial, the current guideline from the American Heart Association and American College of Cardiology recommended TAVI as an alternative to surgery in patients at intermediate surgical risk [18, 48].

**The SURTAVI trial** [47] analyzes the self-expanding CoreValve in intermediaterisk patients and was a randomized, multicenter control trial, which recruited a total of 1746 patients [46]. The combined primary endpoint (all-cause mortality or disabling stroke) at 24 months was 12.6% in the TAVI group and 14.0% in the surgery group. Residual aortic regurgitation and need for pacemaker implantation were more frequent among TAVI patients. In the other hand, SAVR was associated with the higher rates of atrial fibrillation, acute kidney injury, and transfusion requirements. The TAVI resulted in lower mean gradients and larger aortic valve areas than surgery did. Structural valve deterioration at 24 months did not occur in either group. SURTAVI revealed that CoreValve TAVI was not inferior to surgery in patients with intermediate surgical risk [49].

**Bicuspid aortic valves**: the extreme and asymmetrical calcification noted with bicuspid valves can prevent adequate expansion of the valve frame of TAVI valves, affecting valve hemodynamics, and leading to higher aortic valve gradients and more paravalvular leaks [48].

**Prostheses thrombosis**: the Portico Re-sheathable Transcatheter Aortic Valve System U.S. Investigational Device Exemption (PORTICO IDE) study evaluates TAVI with either a Portico valve (St. Jude Medical) or a commercially available valve. Computed tomography (CT) was performed in a subgroup of patients to assess the stent frame of the implanted valve. A finding of reduced leaflet motion on CT in a patient who had had a stroke after TAVI and similar findings in an asymptomatic patient at one clinical site led to a closer look of this observation. Additional CT review by the core laboratory revealed that this finding was not isolated, which prompted a more extensive investigation. This findings encourage to create two registries to evaluate the prostheses thrombosis (SAVORY registry and RESOLVE registry), and find out that therapeutic anticoagulation with warfarin,

**41**

*Current Management of Severe Aortic Stenosis in Intermediate Risk Patients*

but not therapy with antiplatelet drugs, prevented and effectively treated this phenomenon. Better characterization of this observation is needed to determine its

**Durability:** intermediate surgical-risk patients are expected to survive longer after TAVI when compared to higher-risk patients; the broad application of TAVI in low-risk patients should be limited until in vivo durability results are available for the TAVI prostheses [48]. While structural valve deterioration in surgically replaced valves has been thoroughly investigated, long-term follow-up data for TAVI valves

Nowadays, the patients with intermediate risk are in the frontier of TAVI and surgical AVR, and more than ever, the heart team has to be more accurate to choose between the different treatment options available. Current expansion of TAVI into lower surgical risk patients encourages the need to remain cautious about unbridled expansion into those patients, as many questions remain about valve durability, leaflet thrombosis, and higher rates of paravalvular leak and permanent pacemakers [48]. Meanwhile, the surgical approach has improved and evolved to a reduction in surgical aggression. TAVI and minimally invasive aortic valve replacement [51] have become alternatives to surgical aortic valve replacement via median sternotomy (SAVR) to treat severe aortic stenosis (AS). Despite increased interest and utilization, few studies have directly compared TAVI and miniAVR. MiniAVR maintains potential advantages over SAVR, including the implantation of a durable prosthesis and low rates of perioperative myocardial infarction and paravalvular leak. It is associated with longer aortic crossclamp and cardiopulmonary bypass (CPB) times; however, the use of rapid deployment valves can circumvent this. Studies comparing TAVI and miniAVR demonstrate decreased postoperative mortality, valvular regurgitation, and incidence of stroke

From economic point of view, it is clear that for high-risk operable patients, TAVI is currently a more expensive therapy and probably a less effective alternative to surgical AVR, with an incremental cost-effectiveness ratio (ICER) that may be acceptable for high-income countries, but definitely not for the moderate- or low-income countries [52]. When use of TAVI is extended to include a larger number of moderate- to low-risk patients suitable for AVR, overall economic results become less favorable. When manufacturers reduce the exuberant cost of the valve and its accessories, TAVI may become the predominant therapy for patients with severe

Finally, it is clear that both strategies will be the cornerstones in the modern AVR era, but the situations in which to apply each strategy have not yet been clearly delineated. More studies are needed to compare TAVI and miniAVR in low- and intermediate-risk patients. However, the current practice guidelines give a good pathway to choose the adequate therapeutic option in each individual case.

We want to give thanks to the cardiac surgery team at Policlinica de Guipuzcoa and Hospital Clinico Universitario de Valladolid, and especially to our colleagues:

I. Gallo, A. Saenz, I. Perez-Moreiras, and A. Granda y E. Berruti.

*DOI: http://dx.doi.org/10.5772/intechopen.83422*

frequency and evaluate its clinical effect [50].

implanted in patients remain sparse [48].

**8. Conclusions**

in the miniAVR cohorts [51].

aortic stenosis. [52].

**Acknowledgements**

*Current Management of Severe Aortic Stenosis in Intermediate Risk Patients DOI: http://dx.doi.org/10.5772/intechopen.83422*

but not therapy with antiplatelet drugs, prevented and effectively treated this phenomenon. Better characterization of this observation is needed to determine its frequency and evaluate its clinical effect [50].

**Durability:** intermediate surgical-risk patients are expected to survive longer after TAVI when compared to higher-risk patients; the broad application of TAVI in low-risk patients should be limited until in vivo durability results are available for the TAVI prostheses [48]. While structural valve deterioration in surgically replaced valves has been thoroughly investigated, long-term follow-up data for TAVI valves implanted in patients remain sparse [48].

## **8. Conclusions**

*Aortic Stenosis - Current Perspectives*

Valve Implantation trial (SURTAVI trial)) [46, 47].

patients with intermediate surgical risk [49].

more paravalvular leaks [48].

*Heart Team.*

risk [18, 48].

*This cohort of patients has two therapeutic options, surgical AVR or TAVI, and the decision pathway goes through the accurate interpretation of all data by the* 

Nowadays, increased operator experience and enhanced transcatheter valve systems have led to a worldwide trend to use TAVI in patients who are at low or intermediate risk [45]. This tendency has been evaluated in small observational studies, but since most patients who are currently recommended for surgery are at low or intermediate risk, the expansion of the use of TAVI demands more rigorous clinicaltrial validation [46]. The intermediate-surgical-risk trials were approved comparing TAVI to surgery, with the balloon-expandable SAPIEN XT valve (PARTNER 2 trial) and the self-expandable CoreValve (SUrgical Replacement and Transcatheter Aortic

**The PARTNER 2** trial [46] was a multicenter, randomized control trial conducted, which enrolled 2032 patients with severe symptomatic aortic stenosis and intermediate-surgical-risk, and randomized them in a 1:1 fashion across the TAVI arm and the surgical arm [48]. After 2 years, the all-cause mortality or disabling stroke was similar in the TAVI group and the SAVR group (19.3 vs. 21.1%, p = 0.33 and p = 0.001 for **noninferiority**). In the transfemoral access cohort, TAVI demonstrated a lower mortality and disabling stroke (hazard ratio = 0.79; 95% CI = 0.62–1.00; p = 0.05). TAVI resulted in larger aortic valve areas, lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; SAVR resulted in fewer major vascular complications and less paravalvular aortic leak [49]. As a result of the PARTNER 2 trial, the current guideline from the American Heart Association and American College of Cardiology recommended TAVI as an alternative to surgery in patients at intermediate surgical

**The SURTAVI trial** [47] analyzes the self-expanding CoreValve in intermediaterisk patients and was a randomized, multicenter control trial, which recruited a total of 1746 patients [46]. The combined primary endpoint (all-cause mortality or disabling stroke) at 24 months was 12.6% in the TAVI group and 14.0% in the surgery group. Residual aortic regurgitation and need for pacemaker implantation were more frequent among TAVI patients. In the other hand, SAVR was associated with the higher rates of atrial fibrillation, acute kidney injury, and transfusion requirements. The TAVI resulted in lower mean gradients and larger aortic valve areas than surgery did. Structural valve deterioration at 24 months did not occur in either group. SURTAVI revealed that CoreValve TAVI was not inferior to surgery in

**Bicuspid aortic valves**: the extreme and asymmetrical calcification noted with bicuspid valves can prevent adequate expansion of the valve frame of TAVI valves, affecting valve hemodynamics, and leading to higher aortic valve gradients and

**Prostheses thrombosis**: the Portico Re-sheathable Transcatheter Aortic Valve System U.S. Investigational Device Exemption (PORTICO IDE) study evaluates TAVI with either a Portico valve (St. Jude Medical) or a commercially available valve. Computed tomography (CT) was performed in a subgroup of patients to assess the stent frame of the implanted valve. A finding of reduced leaflet motion on CT in a patient who had had a stroke after TAVI and similar findings in an asymptomatic patient at one clinical site led to a closer look of this observation. Additional CT review by the core laboratory revealed that this finding was not isolated, which prompted a more extensive investigation. This findings encourage to create two registries to evaluate the prostheses thrombosis (SAVORY registry and RESOLVE registry), and find out that therapeutic anticoagulation with warfarin,

**40**

Nowadays, the patients with intermediate risk are in the frontier of TAVI and surgical AVR, and more than ever, the heart team has to be more accurate to choose between the different treatment options available. Current expansion of TAVI into lower surgical risk patients encourages the need to remain cautious about unbridled expansion into those patients, as many questions remain about valve durability, leaflet thrombosis, and higher rates of paravalvular leak and permanent pacemakers [48]. Meanwhile, the surgical approach has improved and evolved to a reduction in surgical aggression. TAVI and minimally invasive aortic valve replacement [51] have become alternatives to surgical aortic valve replacement via median sternotomy (SAVR) to treat severe aortic stenosis (AS). Despite increased interest and utilization, few studies have directly compared TAVI and miniAVR. MiniAVR maintains potential advantages over SAVR, including the implantation of a durable prosthesis and low rates of perioperative myocardial infarction and paravalvular leak. It is associated with longer aortic crossclamp and cardiopulmonary bypass (CPB) times; however, the use of rapid deployment valves can circumvent this. Studies comparing TAVI and miniAVR demonstrate decreased postoperative mortality, valvular regurgitation, and incidence of stroke in the miniAVR cohorts [51].

From economic point of view, it is clear that for high-risk operable patients, TAVI is currently a more expensive therapy and probably a less effective alternative to surgical AVR, with an incremental cost-effectiveness ratio (ICER) that may be acceptable for high-income countries, but definitely not for the moderate- or low-income countries [52]. When use of TAVI is extended to include a larger number of moderate- to low-risk patients suitable for AVR, overall economic results become less favorable. When manufacturers reduce the exuberant cost of the valve and its accessories, TAVI may become the predominant therapy for patients with severe aortic stenosis. [52].

Finally, it is clear that both strategies will be the cornerstones in the modern AVR era, but the situations in which to apply each strategy have not yet been clearly delineated. More studies are needed to compare TAVI and miniAVR in low- and intermediate-risk patients. However, the current practice guidelines give a good pathway to choose the adequate therapeutic option in each individual case.

#### **Acknowledgements**

We want to give thanks to the cardiac surgery team at Policlinica de Guipuzcoa and Hospital Clinico Universitario de Valladolid, and especially to our colleagues: I. Gallo, A. Saenz, I. Perez-Moreiras, and A. Granda y E. Berruti.
