**3. Treatment options**

It has been well established that the mortality difference between symptomatic aortic stenosis patients treated with surgery and those treated medically is one of the most striking mortality differences in all of medicine. In fact, it is argued that it is unethical to withhold therapy in symptomatic patients regardless of approach unless there are compelling contraindications. The percent survival of critical aortic stenosis patients is less than 20% at two years compared to a greater than 85% 4- to 5-year survival in those undergoing surgery [3]. A variety of tools have been developed over the years regarding risk assessment for surgery to aid in decision-making. One of the most commonly used is the Society of Thoracic Surgeons predicted risk of mortality calculator [4, 5]. Additional variables include a formal assessment of patient frailty, existing comorbidities and major organ system dysfunction, and technical or anatomical aspects of the procedure that may increase perioperative risks. Putting all of these variables together allows patients to be stratified as low, intermediate, high, and prohibitive risk. These tools are then used to help patients participate in shared decision-making regarding management options as guided by a Heart Team of cardiovascular specialists [6]. Historically, the options for treatment focused on surgery with a variety of biologic and mechanical valve choices – each with advantages and disadvantages, with trade-offs being either durability or the need for lifelong anticoagulation. The development over the past 10 to 15 years of catheter-based options, specifically transaortic valve replacement (TAVR) has resulted in a dramatic increase in therapies offered to patients who otherwise were prohibitive risk [7, 8]. Recent data has allowed for catheter-based therapies to be offered to lower risk populations [9]. However, despite the appeal of catheter-based therapies over conventional openheart surgery, there are still many questions that need to be answered with regards to durability, paravalvular leaks, need for permanent pacemaker implantation, and the growing concerns surrounding both short- and long-term complications that are only slowly being definitively reported. Nevertheless, despite the evolving data and significant amount of industry-driven support stimulating the excitement over transcatheter therapies, combined with the significant costs associated with these based therapies, there are still concerns that surgery might still be the preferred approach for certain patients.

Some of the initial multi-center randomized trials that focused on high and extreme risk patients demonstrated a survival advantage which led to a considerable amount of enthusiasm regarding the potential for catheter-based valves as a viable option for patients who would otherwise die of complications related to their critical aortic stenosis. Following regulatory approval of these devices, additional studies in intermediate and lower risk patients were undertaken. While the selection criteria for intermediate risk patients was based upon their predicted risk of mortality, other significant comorbidities and baseline characteristics were considered in the decision-making. Again, despite the appeal of non-surgical options, the early data in the intermediate risk patient population demonstrated similar all-cause mortality and risk of disabling stroke of around 13 to 14% at two years [10]. These results suggested that catheter-based therapies were non-inferior to surgical approaches, and despite the similarities in outcomes, these findings have often been cited to imply that a non-surgical approach may be preferred by the patients and are even potentially superior with regards to both short- and long-term outcomes when compared to conventional surgery [11]. In fact, while surgery was associated with a period of recovery that impacted formal quality of life assessments, by six months, the objective assessment of quality of life was

**5**

surgical approach.

consented.

*Introductory Chapter: The Evolution of Complex Valve Pathology - The Surgeon's Perspective*

similar in the surgical and catheter-based patients. In addition, similar short- and long-term mortality and stroke risks were seen in low, intermediate, and higher risk patients, again illustrating that both approaches were similar with regards to patient outcomes. Nevertheless, there has been a significant appeal, for a variety of reasons, for trans-catheter therapies, and numerous studies have been undertaken to define which patient characteristics and comorbidities might be better suited for one therapy over the other. A review of 9500 intermediate risk patients enrolled in multiple studies showed no significant benefit of one therapy over another at one year [12]. Similar reviews were also performed in lower risk patients. Specifically looking at the mortality at two years in almost 3500 patients, there was no benefit to a trans-catheter approach over surgery, further emphasizing the concept of noninferior outcomes [13]. In this meta-analysis, there were also similar outcomes with regards to procedure-related stroke. However, there was evidence of a potential 2-year survival advantage for patients undergoing surgery. This survival advantage was also seen in a meta-analysis of intermediate risk patients enrolled in 14 studies consisting of almost 4200 patients. All told, at three years, there appeared to be a significant survival advantage for the intermediate risk patients undergoing surgical aortic valve replacement when compared to trans-catheter therapies [14]. Despite these concerns regarding the long-term outcomes in patients undergoing catheter-based therapies, there have been several randomized multi-center studies exploring their potential role in lower risk patients. The early data has suggested non-inferior outcomes, although some suggest a potential small survival advantage in those undergoing catheter-based therapies with specific types of valves. However, these trials have been heavily criticized. For example, in the PARTNER-3 trial, there was some concern that, despite enrolling low risk patients only, some of the comorbidities and surgical procedures required for these patients implied an inherently much higher risk profile [15]. Furthermore, there was concern that many patients were excluded based upon anatomical considerations, and patient selection might have played a substantial role in reported outcomes favoring catheter-based therapies [16]. Other low risk trials validated some of the shortterm outcome experiences that contributed to regulatory approval with low-risk patients. A fundamental consideration is that low risk is not synonymous with younger patients, and given some of the evolving concerns surrounding intermediate- and long-term survival differences, there are still substantial concerns about offering catheter-based therapies to patients who have a predicted life expectancy beyond several years. Unfortunately, this has not attenuated the astronomical growth of catheter-based therapies at the expense of surgery in a patient population that still, based upon best available evidence, might still benefit from a

The selection bias and concerns of the low-risk trials for TAVR have prompted investigators to report some of the real-world outcomes in similar patients. For example, registry data out of Israel looking at very low risk and low risk patients demonstrated a 10 to 15% two-year mortality, respectively [17]. These outcomes were substantially worse than similar two-year survival rates reported in contemporary surgical studies in which the reported mortality was almost half of those reported in similar TAVR patients [18]. It is unclear if patients are aware of the substantial risks of these procedures when they are making decisions or are being

Clearly, there is still much to learn with regards to the risks, benefits, and patient selection for specific therapies used to treat aortic stenosis. Furthermore, as experiences evolve, especially with the rapid proliferation of transcatheter therapies, there

are still many challenges and unanswered questions.

*DOI: http://dx.doi.org/10.5772/intechopen.95049*

### *Introductory Chapter: The Evolution of Complex Valve Pathology - The Surgeon's Perspective DOI: http://dx.doi.org/10.5772/intechopen.95049*

similar in the surgical and catheter-based patients. In addition, similar short- and long-term mortality and stroke risks were seen in low, intermediate, and higher risk patients, again illustrating that both approaches were similar with regards to patient outcomes. Nevertheless, there has been a significant appeal, for a variety of reasons, for trans-catheter therapies, and numerous studies have been undertaken to define which patient characteristics and comorbidities might be better suited for one therapy over the other. A review of 9500 intermediate risk patients enrolled in multiple studies showed no significant benefit of one therapy over another at one year [12]. Similar reviews were also performed in lower risk patients. Specifically looking at the mortality at two years in almost 3500 patients, there was no benefit to a trans-catheter approach over surgery, further emphasizing the concept of noninferior outcomes [13]. In this meta-analysis, there were also similar outcomes with regards to procedure-related stroke. However, there was evidence of a potential 2-year survival advantage for patients undergoing surgery. This survival advantage was also seen in a meta-analysis of intermediate risk patients enrolled in 14 studies consisting of almost 4200 patients. All told, at three years, there appeared to be a significant survival advantage for the intermediate risk patients undergoing surgical aortic valve replacement when compared to trans-catheter therapies [14]. Despite these concerns regarding the long-term outcomes in patients undergoing catheter-based therapies, there have been several randomized multi-center studies exploring their potential role in lower risk patients. The early data has suggested non-inferior outcomes, although some suggest a potential small survival advantage in those undergoing catheter-based therapies with specific types of valves. However, these trials have been heavily criticized. For example, in the PARTNER-3 trial, there was some concern that, despite enrolling low risk patients only, some of the comorbidities and surgical procedures required for these patients implied an inherently much higher risk profile [15]. Furthermore, there was concern that many patients were excluded based upon anatomical considerations, and patient selection might have played a substantial role in reported outcomes favoring catheter-based therapies [16]. Other low risk trials validated some of the shortterm outcome experiences that contributed to regulatory approval with low-risk patients. A fundamental consideration is that low risk is not synonymous with younger patients, and given some of the evolving concerns surrounding intermediate- and long-term survival differences, there are still substantial concerns about offering catheter-based therapies to patients who have a predicted life expectancy beyond several years. Unfortunately, this has not attenuated the astronomical growth of catheter-based therapies at the expense of surgery in a patient population that still, based upon best available evidence, might still benefit from a surgical approach.

The selection bias and concerns of the low-risk trials for TAVR have prompted investigators to report some of the real-world outcomes in similar patients. For example, registry data out of Israel looking at very low risk and low risk patients demonstrated a 10 to 15% two-year mortality, respectively [17]. These outcomes were substantially worse than similar two-year survival rates reported in contemporary surgical studies in which the reported mortality was almost half of those reported in similar TAVR patients [18]. It is unclear if patients are aware of the substantial risks of these procedures when they are making decisions or are being consented.

Clearly, there is still much to learn with regards to the risks, benefits, and patient selection for specific therapies used to treat aortic stenosis. Furthermore, as experiences evolve, especially with the rapid proliferation of transcatheter therapies, there are still many challenges and unanswered questions.

*Advances in Complex Valvular Disease*

It has been well established that the mortality difference between symptomatic aortic stenosis patients treated with surgery and those treated medically is one of the most striking mortality differences in all of medicine. In fact, it is argued that it is unethical to withhold therapy in symptomatic patients regardless of approach unless there are compelling contraindications. The percent survival of critical aortic stenosis patients is less than 20% at two years compared to a greater than 85% 4- to 5-year survival in those undergoing surgery [3]. A variety of tools have been developed over the years regarding risk assessment for surgery to aid in decision-making. One of the most commonly used is the Society of Thoracic Surgeons predicted risk of mortality calculator [4, 5]. Additional variables include a formal assessment of patient frailty, existing comorbidities and major organ system dysfunction, and technical or anatomical aspects of the procedure that may increase perioperative risks. Putting all of these variables together allows patients to be stratified as low, intermediate, high, and prohibitive risk. These tools are then used to help patients participate in shared decision-making regarding management options as guided by a Heart Team of cardiovascular specialists [6]. Historically, the options for treatment focused on surgery with a variety of biologic and mechanical valve choices – each with advantages and disadvantages, with trade-offs being either durability or the need for lifelong anticoagulation. The development over the past 10 to 15 years of catheter-based options, specifically transaortic valve replacement (TAVR) has resulted in a dramatic increase in therapies offered to patients who otherwise were prohibitive risk [7, 8]. Recent data has allowed for catheter-based therapies to be offered to lower risk populations [9]. However, despite the appeal of catheter-based therapies over conventional openheart surgery, there are still many questions that need to be answered with regards to durability, paravalvular leaks, need for permanent pacemaker implantation, and the growing concerns surrounding both short- and long-term complications that are only slowly being definitively reported. Nevertheless, despite the evolving data and significant amount of industry-driven support stimulating the excitement over transcatheter therapies, combined with the significant costs associated with these based therapies, there are still concerns that surgery might still be the preferred

Some of the initial multi-center randomized trials that focused on high and extreme risk patients demonstrated a survival advantage which led to a considerable amount of enthusiasm regarding the potential for catheter-based valves as a viable option for patients who would otherwise die of complications related to their critical aortic stenosis. Following regulatory approval of these devices, additional studies in intermediate and lower risk patients were undertaken. While the selection criteria for intermediate risk patients was based upon their predicted risk of mortality, other significant comorbidities and baseline characteristics were considered in the decision-making. Again, despite the appeal of non-surgical options, the early data in the intermediate risk patient population demonstrated similar all-cause mortality and risk of disabling stroke of around 13 to 14% at two years [10]. These results suggested that catheter-based therapies were non-inferior to surgical approaches, and despite the similarities in outcomes, these findings have often been cited to imply that a non-surgical approach may be preferred by the patients and are even potentially superior with regards to both short- and long-term outcomes when compared to conventional surgery [11]. In fact, while surgery was associated with a period of recovery that impacted formal quality of life assessments, by six months, the objective assessment of quality of life was

**3. Treatment options**

approach for certain patients.

**4**
