**4. Strategies for improved outcome**

As stated above poor left ventricular function is a negative prognostic factor after aortic valve Replacement regardless the type of the aortic valve disease. Therefore it is important to find objective prognostic variables to identify patients who benefit the most from a surgical intervention and to exclude patients with an excessively high operative risk.

Several studies have reported various approaches to improve postoperative outcome in theses patients.

#### **4.1 B-Type natriuretic peptide as a predictor of heart failure following aortic valve surgery**

Biomarkers, especially pro-BNP have been associated with heart failure and poor ventricular function.

Pro-BNP might be an objective prognostic variable for outcome after surgical aortic valve replacement. (Nozohoor et al. 2009)

NT pro-BNP levels have been to be elevated in patients with aortic valve stenosis. And has already been suggested to monitor the progression of the disease non-invasively as well as to time surgery for aortic stenosis optimally. Further more pro-BNP correlates with endsystolic wallstress in patients with aortic stenosis.

At our department it has become standard of care to administer a 24 hour infusion course of levosimendan 3 days prior to surgery in patients with low EF and high proBNP levels, in order to precondition patients for surgery (data not yet published). In our experience pro-BNP decrease more than 50% on average due to this treatment.

Aortic Valve Surgery and Reduced Ventricular Function 161

Prosthesis patient mismatch (PPM) occurs when the effective orifice area (EOA) of a prosthetic valve is too small relative to the patient's body size. It is graded as moderate if the ratio of effective orifice area (EOA) in cm square to body surface area in m square is <0.85 cm2/m2 and severe if it is <0.65 cm2/m2. PPM has been a controversial topic ever since

Urso et al. concluded in their best evidence topic that there is no strong evidence that moderate patient-prosthesis mismatch (PPM) (indexed IEOA0.85 and >0.65 cm2/m2) is an independent risk factor for 30-day or mid-term overall mortality for adult patients undergoing AVR. An exception could be represented by patients with poor ejection fraction, a condition that can make moderate mismatch a predictor of overall mortality after AVR. On the other hand, severe mismatch is a predictor of overall 30-day or mid-term mortality for patients undergoing AVR independently from the presence of poor ejection fraction. In conclusion, our review suggests that the condition of severe PPM should be always avoided, while the presence of moderate mismatch could be tolerated in patients with normal ejection

Ruel an colleagues concluded that prosthesis–patient mismatch at an indexed effective orifice area of 0.85 cm2/m2 or less after aortic valve replacement primarily affects patients with impaired preoperative left ventricular function and results in decreased survival, lower freedom from heart failure, and incomplete left ventricular mass regression. Patients with impaired left ventricular function represent a critical population in whom prosthesis–patient

There are various ways for reduction of PPM including aortic root enlargement, use of a supra-annular or high performance prosthesis, and the use of a stentless bioprosthesis,

Since heart valve surgery in high-risk patients is associated with considerable morbidity and mortality epidural anaesthesia without mechanical ventilation has been proposed to reduce invasiveness. Bottio et al. showed that heart valve surgery utilising cardiopulmonary bypass is feasible and can be safe using epidural anaesthesia. By maintaining autonomic ventilation, a low mid-term morbidity and mortality was observed in patients in whom there was an

Nevertheless we feel that this is only a niche for cardiac surgical adventurers and only an important step in as far that proof of concept has been demonstrated, however not a method

A substantial number of AS patients have reduced ejection fraction and severe coexisting conditions that preclude surgery. Recently transcatheter aortic-valve implantation (TAVI) has emerged as less invasive and saver alternative for those patients. TAVI can be performed either by a retrograde approach, in which a catheter is inserted through the common femoral artery, or by an antegrade, transapical approach, in which a catheter is inserted through the apex of the left ventricle with the use of an anterolateral thoracotomy. (Lazar, 2010) Initially single-center, nonrandomized trials have shown the feasibility of TAVI in patients who are not suitable candidates for surgical replacement of the aortic

mismatch should be avoided at the time of aortic valve replacement. (Ruel 2005)

valves have been implanted. (Mascherbauer, 2008; Yap CH 2007))

fraction without any impact on overall survival. (Urso 2009)

aortic homograft, or pulmonary autograft. (Hashimoto 2006)

**4.4 The awake patient in cardiac surgeons** 

unacceptable operative risk. (Bottio 2007)

**4.5 Future perspectives** 

we would recommend to any of our patients.

valve. (Himbert et al. 2009, Webb et al. 2009)

**4.5.1 Transcatheter aortic valve implantation (TAVI)** 

**4.3 Prosthesis patient mismatch** 

Järvelä et al. investigated the impact of levosimendan in aortic valve surgery. A total of 24 patients were included in this study, 12 per arm however only with a moderate reduction in pump-function (treatment group 48%, control 54%). Levosimendan was started at induction of anaesthesia and continued over 24 hours. While induction of anesthesia led to reduction of EF in both groups, ejection fraction slowly recovered almost to preoperative levels in the control group. In contrast to that the ejection fraction of patients receiving levosimendan even improved in comparison to the preoperative levels. (Figure 7). (Järvelä et al. 2008) Eventhough the preoperative ejection fraction was only moderately reduced. The application of levosimendan led to an improvement of EF. This seems rather promising especially when having in mind, that patients with severely reduced EF don not improve in ventricular function after aortic valve replacement without any concomitant treatment.

Reprinted with permission of Circulation

Fig. 7. Effects of levosimendan on cardiac performance and recovery in aortic valve surgery (Järvelä et al. 2008)

#### **4.2 Statins**

Statins have become a blockbuster drug primarily for artherosclerotic diseases, but they have pleotropic effects. This triggered the interest on potential beneficial effects of these drugs for other indications like aortic aneurysms and calcific valvular heart disease.

Considerations regarding statin-therapy for valvular heart diseases are on the one hand slower progression of calcification in patients with aortic stenosis and on the other hand there are studies showing that statin therapy improves the outcome after aortic valve replacement.

Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid lowering studies have had conflicting results. There are studies suggesting statin-therapy for every patient with aortic stenosis. (Fedoruk et al. 2008) However Rossebo et al. showed that statin-therapy did not reduce the composite outcome of combined aortic-valve events and ischemic events in AS patients. Statin-therapy resulted in reduced incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis. (Rossebo et al. 2008) Nevertheless the overall outcome of patients with statin-therapy in this study was superior to those without statin-therapy, this might be due to the fact that a high percentage of AS patient have concomitant ischemic cardiovascular diseases. Therefore we would suggest statin-therapy as standard of care for every patient with aortic stenosis.

#### **4.3 Prosthesis patient mismatch**

160 Aortic Valve Surgery

Järvelä et al. investigated the impact of levosimendan in aortic valve surgery. A total of 24 patients were included in this study, 12 per arm however only with a moderate reduction in pump-function (treatment group 48%, control 54%). Levosimendan was started at induction of anaesthesia and continued over 24 hours. While induction of anesthesia led to reduction of EF in both groups, ejection fraction slowly recovered almost to preoperative levels in the control group. In contrast to that the ejection fraction of patients receiving levosimendan even improved in comparison to the preoperative levels. (Figure 7). (Järvelä et al. 2008) Eventhough the preoperative ejection fraction was only moderately reduced. The application of levosimendan led to an improvement of EF. This seems rather promising especially when having in mind, that patients with severely reduced EF don not improve in ventricular function after aortic valve replacement without any concomitant treatment.

Fig. 7. Effects of levosimendan on cardiac performance and recovery in aortic valve surgery

Statins have become a blockbuster drug primarily for artherosclerotic diseases, but they have pleotropic effects. This triggered the interest on potential beneficial effects of these

Considerations regarding statin-therapy for valvular heart diseases are on the one hand slower progression of calcification in patients with aortic stenosis and on the other hand there are studies showing that statin therapy improves the outcome after aortic valve

Hyperlipidemia has been suggested as a risk factor for stenosis of the aortic valve, but lipid lowering studies have had conflicting results. There are studies suggesting statin-therapy for every patient with aortic stenosis. (Fedoruk et al. 2008) However Rossebo et al. showed that statin-therapy did not reduce the composite outcome of combined aortic-valve events and ischemic events in AS patients. Statin-therapy resulted in reduced incidence of ischemic cardiovascular events but not events related to aortic-valve stenosis. (Rossebo et al. 2008) Nevertheless the overall outcome of patients with statin-therapy in this study was superior to those without statin-therapy, this might be due to the fact that a high percentage of AS patient have concomitant ischemic cardiovascular diseases. Therefore we would suggest

drugs for other indications like aortic aneurysms and calcific valvular heart disease.

statin-therapy as standard of care for every patient with aortic stenosis.

Reprinted with permission of Circulation

(Järvelä et al. 2008)

**4.2 Statins** 

replacement.

Prosthesis patient mismatch (PPM) occurs when the effective orifice area (EOA) of a prosthetic valve is too small relative to the patient's body size. It is graded as moderate if the ratio of effective orifice area (EOA) in cm square to body surface area in m square is <0.85 cm2/m2 and severe if it is <0.65 cm2/m2. PPM has been a controversial topic ever since valves have been implanted. (Mascherbauer, 2008; Yap CH 2007))

Urso et al. concluded in their best evidence topic that there is no strong evidence that moderate patient-prosthesis mismatch (PPM) (indexed IEOA0.85 and >0.65 cm2/m2) is an independent risk factor for 30-day or mid-term overall mortality for adult patients undergoing AVR. An exception could be represented by patients with poor ejection fraction, a condition that can make moderate mismatch a predictor of overall mortality after AVR. On the other hand, severe mismatch is a predictor of overall 30-day or mid-term mortality for patients undergoing AVR independently from the presence of poor ejection fraction. In conclusion, our review suggests that the condition of severe PPM should be always avoided, while the presence of moderate mismatch could be tolerated in patients with normal ejection fraction without any impact on overall survival. (Urso 2009)

Ruel an colleagues concluded that prosthesis–patient mismatch at an indexed effective orifice area of 0.85 cm2/m2 or less after aortic valve replacement primarily affects patients with impaired preoperative left ventricular function and results in decreased survival, lower freedom from heart failure, and incomplete left ventricular mass regression. Patients with impaired left ventricular function represent a critical population in whom prosthesis–patient mismatch should be avoided at the time of aortic valve replacement. (Ruel 2005)

There are various ways for reduction of PPM including aortic root enlargement, use of a supra-annular or high performance prosthesis, and the use of a stentless bioprosthesis, aortic homograft, or pulmonary autograft. (Hashimoto 2006)

#### **4.4 The awake patient in cardiac surgeons**

Since heart valve surgery in high-risk patients is associated with considerable morbidity and mortality epidural anaesthesia without mechanical ventilation has been proposed to reduce invasiveness. Bottio et al. showed that heart valve surgery utilising cardiopulmonary bypass is feasible and can be safe using epidural anaesthesia. By maintaining autonomic ventilation, a low mid-term morbidity and mortality was observed in patients in whom there was an unacceptable operative risk. (Bottio 2007)

Nevertheless we feel that this is only a niche for cardiac surgical adventurers and only an important step in as far that proof of concept has been demonstrated, however not a method we would recommend to any of our patients.

#### **4.5 Future perspectives**

#### **4.5.1 Transcatheter aortic valve implantation (TAVI)**

A substantial number of AS patients have reduced ejection fraction and severe coexisting conditions that preclude surgery. Recently transcatheter aortic-valve implantation (TAVI) has emerged as less invasive and saver alternative for those patients. TAVI can be performed either by a retrograde approach, in which a catheter is inserted through the common femoral artery, or by an antegrade, transapical approach, in which a catheter is inserted through the apex of the left ventricle with the use of an anterolateral thoracotomy. (Lazar, 2010) Initially single-center, nonrandomized trials have shown the feasibility of TAVI in patients who are not suitable candidates for surgical replacement of the aortic valve. (Himbert et al. 2009, Webb et al. 2009)

Aortic Valve Surgery and Reduced Ventricular Function 163

In 2011 Leon and his coauthors report the results of the placement of Aortic Transcatheter Valves (PARTNER) trial, a prospective, randomized, multicenter trial to determine the optimal method of treating patients with critical aortic stenosis who are considered not to be suitable candidates for surgery. This revealed promising results showed a 20% reduction in mortality in comparison to medical treatment alone in patients with significant aortic stenosis not suitable for surgery. Furthermore the trial revealed that TAVI can achieve

Another step towards reduction of operative time and thus lowering the burden of surgical intervention for the patient is the invention of sutureless aortic bioprosthesis. Currently there are 3 different valve types on the market: Perceval (Sorin), Enable (ATS, Medical) and Aortic Quick Connect (Edwards Lifesciences). They require only three stitches at the nadirs of the annulus to navigate the valve into the right plane prior to deployment of the nitinol stent. Initial clinical experience with these valves was satisfactory revealing promising results. In case of the Perceval valve the study investigators were able to implant a wellfunctioning sutureless stent-mounted valve in the aortic position in less than 20 minutes of aortic crossclamping. This was associated with excellent early clinical and hemodynamic outcome in high-risk patients. (Flameng et al. 2011). The sutureless valve implantation technique is also feasible and safe with the ATS 3f Enable Bioprosthesis. Valve implantation resulted in excellent hemodynamics and significant clinical improvement. Overall, these data confirm the safety and clinical utility of the Enable(®) Bioprosthesis for aortic valve replacement. (Martens et al., 2011) Data for the most recent sutureless valve to appear on the

The quick implantation procedure shortens the operative time, in particular the cross clamp time. Which has been shown to be a variable for poor outcome after aortic valve

Aortic-valve replacement or transcatheter aortic valve implantation are the most effective treatments to alleviate symptoms and improve survival in patients with critical aortic stenosis. Aortic valve disease especially stenosis is on the rise as it is primarily a disease of the elderly. Patients with decreased EF are clearly a high risk population, demonstrating both increased morbidity and mortality after aortic valve surgery. However in this chapter we could show that the cardiovascular medical community has so far responded to this challenge by devising new strategies to cope with the problem of an ever sicker patient population. A substantial number of these patients with coexisting conditions that used to preclude surgery are nowadays treated by less invasive approaches like TAVI. Furthermore there is progress on many fronts: Serum markers like BNP will help to time the intervention, levosimendan is already employed to precondition the patients prior to surgical interventions. New technologies like sutureless valves and TAVI significantly reduced the burden of the intervention. Apart from these new inventions one of the most important strategies to improve the outcome of patients undergoing aortic valve replacement with and without impaired left ventricular function is meticulous surgical

similar results as surgery in high risk patients. (Leon 2011)

market, the Aortic Quick Connect, are also excellent. (Kocher et al., 2011)

**4.5.2 Sutureless aortic valve bio prostheses** 

replacement.

**5. Conclusion** 

performance.

Fig. 8. Implantation of an Aortic Quick Connect Bioprosthetic valve (Edwards Lifesciences)

Fig. 8. Implantation of an Aortic Quick Connect Bioprosthetic valve (Edwards Lifesciences)

In 2011 Leon and his coauthors report the results of the placement of Aortic Transcatheter Valves (PARTNER) trial, a prospective, randomized, multicenter trial to determine the optimal method of treating patients with critical aortic stenosis who are considered not to be suitable candidates for surgery. This revealed promising results showed a 20% reduction in mortality in comparison to medical treatment alone in patients with significant aortic stenosis not suitable for surgery. Furthermore the trial revealed that TAVI can achieve similar results as surgery in high risk patients. (Leon 2011)

#### **4.5.2 Sutureless aortic valve bio prostheses**

Another step towards reduction of operative time and thus lowering the burden of surgical intervention for the patient is the invention of sutureless aortic bioprosthesis. Currently there are 3 different valve types on the market: Perceval (Sorin), Enable (ATS, Medical) and Aortic Quick Connect (Edwards Lifesciences). They require only three stitches at the nadirs of the annulus to navigate the valve into the right plane prior to deployment of the nitinol stent. Initial clinical experience with these valves was satisfactory revealing promising results. In case of the Perceval valve the study investigators were able to implant a wellfunctioning sutureless stent-mounted valve in the aortic position in less than 20 minutes of aortic crossclamping. This was associated with excellent early clinical and hemodynamic outcome in high-risk patients. (Flameng et al. 2011). The sutureless valve implantation technique is also feasible and safe with the ATS 3f Enable Bioprosthesis. Valve implantation resulted in excellent hemodynamics and significant clinical improvement. Overall, these data confirm the safety and clinical utility of the Enable(®) Bioprosthesis for aortic valve replacement. (Martens et al., 2011) Data for the most recent sutureless valve to appear on the market, the Aortic Quick Connect, are also excellent. (Kocher et al., 2011)

The quick implantation procedure shortens the operative time, in particular the cross clamp time. Which has been shown to be a variable for poor outcome after aortic valve replacement.

## **5. Conclusion**

Aortic-valve replacement or transcatheter aortic valve implantation are the most effective treatments to alleviate symptoms and improve survival in patients with critical aortic stenosis. Aortic valve disease especially stenosis is on the rise as it is primarily a disease of the elderly. Patients with decreased EF are clearly a high risk population, demonstrating both increased morbidity and mortality after aortic valve surgery. However in this chapter we could show that the cardiovascular medical community has so far responded to this challenge by devising new strategies to cope with the problem of an ever sicker patient population. A substantial number of these patients with coexisting conditions that used to preclude surgery are nowadays treated by less invasive approaches like TAVI. Furthermore there is progress on many fronts: Serum markers like BNP will help to time the intervention, levosimendan is already employed to precondition the patients prior to surgical interventions. New technologies like sutureless valves and TAVI significantly reduced the burden of the intervention. Apart from these new inventions one of the most important strategies to improve the outcome of patients undergoing aortic valve replacement with and without impaired left ventricular function is meticulous surgical performance.

Aortic Valve Surgery and Reduced Ventricular Function 165

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Patients with an aortic valve pathology and a severely reduced ejection fraction constitute a significant challenge. However, in light of the recent inventions, innovations, new technologies and strategies for this patient cohort we are positive that the scientist and medical professionals in the field of cardiovascular medicine will be able to tackle this problem.
