**2. Rationale for proposing surgical AVR for the elderly**

#### **2.1 Natural history of severe AS**

Above all, the natural history of severe aortic stenosis (SAS) has a dismal prognosis. Once symptoms appear, life expectancy is 5 years for angina, 3 years for dyspnea or syncope and 2 years for cardiac failure (Chizner et al., 1980; Ross and Braunwald, 1968). Even though those results were obtained from old studies conducted during the 1960s and 1970s (Chizner et al., 1980; Horstkotte & Loogen, 1988; Ross & Braunwald, 1968), concerned young patients

Relationship Between Aortic Valve Replacement and Old Age 169

role of aging itself on organ decline is difficult to demonstrate. Indeed, a study on elderly individuals in very good health (old senior athletes) often had physiological cardiovascular system performances quite close to those of younger athletes but that is not the case for their osteoarticular system! Thus, the descriptions of so-called changes 'linked' to aging (i.e., frequent or typical of the old-old), be they histological or physiological performances, are the means of populations heterogeneous in terms of life style, exposures to personal or environmental risk factors and pathologies. When an attempt was made to show the same 'age-linked' changes exclusively in healthy aged or physically fit subjects, none was found (Somme et al., 2009). Hence, defining the slope of line 1 for individuals is difficult (Fig. 1), as it depends, organ by organ, on personal and environmental factors. Nevertheless, it could be useful to predict vulnerability, like an old person's response to treatment or knowing his/her level of physical activity, which is probably a better marker of physiological cardiovascular aging than chronological age. It is widely accepted that, for the young subject, cardiac function is the main parameter conditioning the maximal stress level, whereas for the elderly subject, it seems more often to be limited by respiratory function (Chan & Welsch, 1998). Finally, physiological aging can be represented as the functional state of adaptation mechanisms (or reserves) that are overwhelmed during stress or effort. These physiological particularities render the elderly more susceptible to acute diseases. This frailty should not limit access to intensive care for old patients, but should rather plead

1+2+3 1+2 1+3

Fig. 1. Organ decline (regardless of the organ) due to aging is represented by slope 1. Two types of events are able to shift this organ under the threshold (dashed line) of organ insufficiency: a chronic (according to slope 2) or acute disease (the steepest slope 3).

In practice, old age is defined 2 ways: that set by a chronological age and a dynamic

approach taking into consideration the evolution of the health of the population.

Adapted from 1+2+3: how to be effective in geriatrics? (Bouchon, 1984)

**2.5 Threshold of old age** 

1

in favor of their adapted and early management.

(20 and 60 years old) and included small numbers of patients (15–55), more recent publications continue to emphasize the very poor natural history of SAS (Schueler et al., 2010; Varadarajan et al., 2006).

#### **2.2 Failure of medical treatment**

The introduction of medical treatments, such as beta-blockers, statins and angiotensinconverting–enzyme inhibitors, has not specifically modified SAS prognosis (Schueler et al., 2010). Recently, Schueler et al. prospectively compared the prognoses of medically treated elderly SAS patients (mean age: 86 years) at high surgical risk to age- and sex-matched patients with non-severe AS; at 2 years, 41.8% and 59.8%, respectively, were survivors. Independent factors associated with death of SAS patients were Society Thoracic Surgeons predicted risk of mortality (STS-PROM) score (Shroyer et al., 2003), pulmonary arterial pressure >30 mm Hg, creatinine and diabetes (Schueler et al., 2010). Scharwz et al. (1982) compared the prognoses of 135 SAS patients treated surgically with AVR versus 19 denied surgery: at 3 years, 87% of the surgical group were alive vs 21% of medically treated group (p<0.001). Varadarajan et al. (2006) showed that conservatively treated SAS patients had poorer outcomes, with respective 1-, 5- and 10-year survival rates of 62%, 32% and 18%.

#### **2.3 Failure of balloon aortic valvuloplasty**

Although balloon aortic valvuloplasty (BAV) acutely increases the aortic valve area and attenuates symptoms, neither change significantly improved prognosis, with high mortality and complication rates (NHLBI Balloon Valvuloplasty Registry participants, 1991). Moreover, its restenosis rate at 1 year was >80% (Eltchaninoff et al., 1995). Current indications for BAV are very limited, with valvuloplasty primarily considered a bridge to surgery or transvalvular aortic implantation (TAVI) in hemodynamically unstable patients (Vahanian and Otto, 2010).

Thus, for the time being, surgical AVR remains the treatment of choice for SAS. Notably, the international recommendations do not provide any specific guidelines concerning age (Bonow et al., 2006; Vahanian et al., 2007).

#### **2.4 Age, aging and prognosis**

Age is a known independent risk factor for in-hospital mortality after admission to the intensive care unit after cardiac surgery (Knaus et al., 1993; Roques & Nashef, 2003). However, although disease severity assessed with APACHE III can explain 80% of inhospital deaths, age can explain only 13% (Knaus et al., 1993). The mechanism of excess death independent of elderly patients' disease severity has not yet been clearly elucidated. Setting aside the excess mortality linked to less intensive treatment of the elderly, it could be intrinsic, because of the greater vulnerability to disease, or extrinsic, attributable to a poorer response or even poorer tolerance of the therapeutic modalities used in intensive care. For both hypotheses, physiological particularities specific to the older patient are implicated. From a global perspective, Bouchon (1984) proposed a model in which morbidity of elderly patients resulted from 3 components (Figure 1).

Clinically detectable morbidity is usually the sum of organ aging, possible organic deterioration resulting from more-or-less quiescent chronic disease and deterioration appended by acute disease. We cannot detail here all those deteriorations organ-by-organ (Somme et al., 2009), but retain the broad lines that transcend organ specificities. First, the

(20 and 60 years old) and included small numbers of patients (15–55), more recent publications continue to emphasize the very poor natural history of SAS (Schueler et al.,

The introduction of medical treatments, such as beta-blockers, statins and angiotensinconverting–enzyme inhibitors, has not specifically modified SAS prognosis (Schueler et al., 2010). Recently, Schueler et al. prospectively compared the prognoses of medically treated elderly SAS patients (mean age: 86 years) at high surgical risk to age- and sex-matched patients with non-severe AS; at 2 years, 41.8% and 59.8%, respectively, were survivors. Independent factors associated with death of SAS patients were Society Thoracic Surgeons predicted risk of mortality (STS-PROM) score (Shroyer et al., 2003), pulmonary arterial pressure >30 mm Hg, creatinine and diabetes (Schueler et al., 2010). Scharwz et al. (1982) compared the prognoses of 135 SAS patients treated surgically with AVR versus 19 denied surgery: at 3 years, 87% of the surgical group were alive vs 21% of medically treated group (p<0.001). Varadarajan et al. (2006) showed that conservatively treated SAS patients had poorer outcomes, with respective 1-, 5- and 10-year survival rates of 62%, 32% and 18%.

Although balloon aortic valvuloplasty (BAV) acutely increases the aortic valve area and attenuates symptoms, neither change significantly improved prognosis, with high mortality and complication rates (NHLBI Balloon Valvuloplasty Registry participants, 1991). Moreover, its restenosis rate at 1 year was >80% (Eltchaninoff et al., 1995). Current indications for BAV are very limited, with valvuloplasty primarily considered a bridge to surgery or transvalvular aortic implantation (TAVI) in hemodynamically unstable patients

Thus, for the time being, surgical AVR remains the treatment of choice for SAS. Notably, the international recommendations do not provide any specific guidelines concerning age

Age is a known independent risk factor for in-hospital mortality after admission to the intensive care unit after cardiac surgery (Knaus et al., 1993; Roques & Nashef, 2003). However, although disease severity assessed with APACHE III can explain 80% of inhospital deaths, age can explain only 13% (Knaus et al., 1993). The mechanism of excess death independent of elderly patients' disease severity has not yet been clearly elucidated. Setting aside the excess mortality linked to less intensive treatment of the elderly, it could be intrinsic, because of the greater vulnerability to disease, or extrinsic, attributable to a poorer response or even poorer tolerance of the therapeutic modalities used in intensive care. For both hypotheses, physiological particularities specific to the older patient are implicated. From a global perspective, Bouchon (1984) proposed a model in which morbidity of elderly

Clinically detectable morbidity is usually the sum of organ aging, possible organic deterioration resulting from more-or-less quiescent chronic disease and deterioration appended by acute disease. We cannot detail here all those deteriorations organ-by-organ (Somme et al., 2009), but retain the broad lines that transcend organ specificities. First, the

2010; Varadarajan et al., 2006).

**2.2 Failure of medical treatment** 

**2.3 Failure of balloon aortic valvuloplasty** 

(Bonow et al., 2006; Vahanian et al., 2007).

patients resulted from 3 components (Figure 1).

(Vahanian and Otto, 2010).

**2.4 Age, aging and prognosis** 

role of aging itself on organ decline is difficult to demonstrate. Indeed, a study on elderly individuals in very good health (old senior athletes) often had physiological cardiovascular system performances quite close to those of younger athletes but that is not the case for their osteoarticular system! Thus, the descriptions of so-called changes 'linked' to aging (i.e., frequent or typical of the old-old), be they histological or physiological performances, are the means of populations heterogeneous in terms of life style, exposures to personal or environmental risk factors and pathologies. When an attempt was made to show the same 'age-linked' changes exclusively in healthy aged or physically fit subjects, none was found (Somme et al., 2009). Hence, defining the slope of line 1 for individuals is difficult (Fig. 1), as it depends, organ by organ, on personal and environmental factors. Nevertheless, it could be useful to predict vulnerability, like an old person's response to treatment or knowing his/her level of physical activity, which is probably a better marker of physiological cardiovascular aging than chronological age. It is widely accepted that, for the young subject, cardiac function is the main parameter conditioning the maximal stress level, whereas for the elderly subject, it seems more often to be limited by respiratory function (Chan & Welsch, 1998). Finally, physiological aging can be represented as the functional state of adaptation mechanisms (or reserves) that are overwhelmed during stress or effort. These physiological particularities render the elderly more susceptible to acute diseases. This frailty should not limit access to intensive care for old patients, but should rather plead in favor of their adapted and early management.

Fig. 1. Organ decline (regardless of the organ) due to aging is represented by slope 1. Two types of events are able to shift this organ under the threshold (dashed line) of organ insufficiency: a chronic (according to slope 2) or acute disease (the steepest slope 3). Adapted from 1+2+3: how to be effective in geriatrics? (Bouchon, 1984)

#### **2.5 Threshold of old age**

In practice, old age is defined 2 ways: that set by a chronological age and a dynamic approach taking into consideration the evolution of the health of the population.

Relationship Between Aortic Valve Replacement and Old Age 171

2009). Descriptions of the complications, their definitions, their characteristics and rates varied widely from one study to another. The most frequent complications are transfusion (48.8–81.4%), new onset supraventricular arrhythmia (31.2–45.2%), low cardiac output (16.7–35.7%), prolonged mechanical ventilation (≥24 hours) (22–26%), reoperation for bleeding (6–9%), permanent strokes (3–6%), acute renal failure (4.6–12%), infections (2.4–5.6%) and heart block requiring a pacemaker (2.3–5%) (Collart et al., 2005; Kohl et al., 2007; Maillet et

I AVR Mean

66% 50% 50% 50% 50% 100% 45% 42% 100% 33.1% NR 74% 62.1% 85.2% 77.8% 27.2% 57% 76% 25% 100% 100% 49% 51% 52%

Table 2. Postoperative mortality rates after AVR with/without CABG for octogenarians

At intermediate term, all studies documented impressive symptom regression, with 73.2– 92.5% of the survivors being in New York Heart Association (NYHA) classification I or II (Collart et al., 2005; Kolh et al., 2007; Maillet et al., 2009,). The mean NYHA classification of survivors fell from 3.1 to 1.7 (p<0.001) (Sundt et al., 2000). Lastly, 91% of survivors were

age, yr

Overall operative mortality

> NR 9.4% 12.5% 12.7 15.7% 14% 17.5% 4.5% 6.6% 11% 3.4% 8.8% 8.5% 10.1% 7.5% 9.8% 9% 13% 4.4% 5.7% 9.2% 16.7% 8.4% 7.8%

Operative mortality I AVR AVR+CABG

> 23.5% 16.1% 16.6% 19.4% 17.9%

> 27.7% 6.6%

> > NR NR NR NR NR NR 9.7% NR 24% NR

25.7% 9.5% NR

30% 3.2% 8.3% 5.7% 9.6% 14% 5.2% 1.8% 6.6% NR NR NR NR NR NR 9.4% 10% 9% NR 5.7% 9.2% 10.2% 7.6% NR

al., 2009; Melby et al. 2007; Sundt et al., 2000; Thourani et al., 2008).

period

1976–1987 1974–1987 1983–1986 1976–1988 1982–1986 1981–1989 1975–1991 1982–1992 1986–1995 1993–1998 1990–1993 1993–2003 1992–2003 1978–2003 2000–2004 1996–2003 1993–2005 1992–2004 1999–2003 1996–2006 1995–2006 1998–2003 1996–2006 2005–2007

First Author Year N Study

AVR = aortic valve replacement; I AVR = isolated AVR; CABG = coronary artery bypass graft; NR = not reported.

Edmunds Levinson Bashour Culliford Freeman Olsson Elayda Tsai

Asimakopoulos

between 1976 and 2010

**2.7 Intermediate-term AVR results** 

angina-free (Kolh et al., 2007).

Sundt Sjögren Collart Chiappini Langanay Langanay Stoica Melby Kolh Huber Thourani Leonteyv Maillet Florath Folkmann

The fixed chronological age definition (around 65–75 years for young-old; between 75–80 and 85–90 for the old-old, and >85–90 for the oldest-old) is the most extensively used in the medical literature. It has the advantages of enabling comparisons between published historical data and not encouraging interpretation. However, it does not account for the evolution of life expectancy at 60 years and, even less, its evolution without handicap(s). Indeed, life expectancy for a 60-year-old man in France increased from 15.4 to 21.7 years between 1950 and 2010. This prolongation obviously has an impact on the premonitory usefulness of aggressive therapies, like cardiac surgery after 60 years during that interval. A dynamic definition of the old-age threshold can take those aspects into consideration. Several can be proposed but one seems readily accessible: survival at life expectancy at birth (Table 1). If we accept this definition, the percentage of 'aged' individuals (so defined) in France did not increase between 1950 (~11%) and 2010 (~9%), because life expectancy rose

more quickly than the number of aged persons.


Table 1. 1950 to 2010: Evolution of life expectancy in France and the aged population

Age has always been identified as a major risk factor for mortality after cardiac surgery (Roques et al., 2003; Shroyer et al., 2003), but the mean age of operated patients is rising. Indeed, surgery on octogenarians is performed daily in western countries. Are there some limits for age and cardiac surgery? Florath et al. (2010) identified >84 years as an important independent risk factor for mortality 6 months after AVR for octogenarians. However, some publications indicated that surgeons seem less-and-less reluctant to operate on nonagenarians (Edwards et al., 2003; Praschker et al., 2006). During the 1980s, the age limit for cardiac surgery was progressively increased >80 years without drama considering outcomes (Edmunds et al., 1988). Should the story repeat itself for nonagenarians or even centenarians in the future?

#### **2.6 Postoperative outcomes of surgical AVR for octogenarians**

Surgical AVR results for octogenarians are acceptable and compare favorably with those of younger patients (Alexander et al., 2000; Thourani et al., 2008). Table 2 summarizes the early postoperative mortality (≤30 days) rate after AVR for octogenarians.

De facto, studies during the 1990s and 2000s included more patients than during 1980s. For example, in the UK, between 1996 and 2003, the rate of surgery performed on octogenarians increased 2-fold, from 4.1% to 9.8% (Stoica et al., 2006). For the studies with >200 patients, early in-hospital mortality (≤30 days) ranged from 6.6% to 10.1%. Very few studies included only patients with isolated AVR (Table 2). Most studies included AVR with and without coronary-artery bypass graft (CABG). Postoperative mortality rates were higher when CABG was combined with AVR compared to AVR alone.

However, the postoperative morbidity rate was very high for octogenarians after AVR (Melby et al., 2007; Thourani et al., 2008) and more than two-thirds of octogenarians will develop ≥1 postoperative complications (Collart et al., 2005; Kolh et al., 2007; Maillet et al.,

The fixed chronological age definition (around 65–75 years for young-old; between 75–80 and 85–90 for the old-old, and >85–90 for the oldest-old) is the most extensively used in the medical literature. It has the advantages of enabling comparisons between published historical data and not encouraging interpretation. However, it does not account for the evolution of life expectancy at 60 years and, even less, its evolution without handicap(s). Indeed, life expectancy for a 60-year-old man in France increased from 15.4 to 21.7 years between 1950 and 2010. This prolongation obviously has an impact on the premonitory usefulness of aggressive therapies, like cardiac surgery after 60 years during that interval. A dynamic definition of the old-age threshold can take those aspects into consideration. Several can be proposed but one seems readily accessible: survival at life expectancy at birth (Table 1). If we accept this definition, the percentage of 'aged' individuals (so defined) in France did not increase between 1950 (~11%) and 2010 (~9%), because life expectancy rose

Life expectancy at birth for males, years 63.4 78.1 Life expectancy at birth for females, years 69.2 84.8

Persons >75 years old in the population 9% Table 1. 1950 to 2010: Evolution of life expectancy in France and the aged population

Age has always been identified as a major risk factor for mortality after cardiac surgery (Roques et al., 2003; Shroyer et al., 2003), but the mean age of operated patients is rising. Indeed, surgery on octogenarians is performed daily in western countries. Are there some limits for age and cardiac surgery? Florath et al. (2010) identified >84 years as an important independent risk factor for mortality 6 months after AVR for octogenarians. However, some publications indicated that surgeons seem less-and-less reluctant to operate on nonagenarians (Edwards et al., 2003; Praschker et al., 2006). During the 1980s, the age limit for cardiac surgery was progressively increased >80 years without drama considering outcomes (Edmunds et al., 1988). Should the story repeat itself for nonagenarians or even centenarians

Surgical AVR results for octogenarians are acceptable and compare favorably with those of younger patients (Alexander et al., 2000; Thourani et al., 2008). Table 2 summarizes the early

De facto, studies during the 1990s and 2000s included more patients than during 1980s. For example, in the UK, between 1996 and 2003, the rate of surgery performed on octogenarians increased 2-fold, from 4.1% to 9.8% (Stoica et al., 2006). For the studies with >200 patients, early in-hospital mortality (≤30 days) ranged from 6.6% to 10.1%. Very few studies included only patients with isolated AVR (Table 2). Most studies included AVR with and without coronary-artery bypass graft (CABG). Postoperative mortality rates were higher when

However, the postoperative morbidity rate was very high for octogenarians after AVR (Melby et al., 2007; Thourani et al., 2008) and more than two-thirds of octogenarians will develop ≥1 postoperative complications (Collart et al., 2005; Kolh et al., 2007; Maillet et al.,

Persons >65 years old in the population 11.4%

**2.6 Postoperative outcomes of surgical AVR for octogenarians** 

postoperative mortality (≤30 days) rate after AVR for octogenarians.

CABG was combined with AVR compared to AVR alone.

1950 2010

more quickly than the number of aged persons.

in the future?

2009). Descriptions of the complications, their definitions, their characteristics and rates varied widely from one study to another. The most frequent complications are transfusion (48.8–81.4%), new onset supraventricular arrhythmia (31.2–45.2%), low cardiac output (16.7–35.7%), prolonged mechanical ventilation (≥24 hours) (22–26%), reoperation for bleeding (6–9%), permanent strokes (3–6%), acute renal failure (4.6–12%), infections (2.4–5.6%) and heart block requiring a pacemaker (2.3–5%) (Collart et al., 2005; Kohl et al., 2007; Maillet et al., 2009; Melby et al. 2007; Sundt et al., 2000; Thourani et al., 2008).


AVR = aortic valve replacement; I AVR = isolated AVR;

CABG = coronary artery bypass graft; NR = not reported.

Table 2. Postoperative mortality rates after AVR with/without CABG for octogenarians between 1976 and 2010

#### **2.7 Intermediate-term AVR results**

At intermediate term, all studies documented impressive symptom regression, with 73.2– 92.5% of the survivors being in New York Heart Association (NYHA) classification I or II (Collart et al., 2005; Kolh et al., 2007; Maillet et al., 2009,). The mean NYHA classification of survivors fell from 3.1 to 1.7 (p<0.001) (Sundt et al., 2000). Lastly, 91% of survivors were angina-free (Kolh et al., 2007).

Relationship Between Aortic Valve Replacement and Old Age 173

comparable to that predicted for the general population >75 years old. Olsson et al. (1996), prospectively compared QOL evolution for 2 groups of patients referred for isolated AVR; 30 octogenarians vs 30 patients 65–75 years old. At 1-year postAVR, octogenarians, despite their more compromised preoperative status, had markedly regressed symptoms, and their physical abilities and general well-being were of a similar magnitude to those of the younger patients. Those improvements appeared as of 3 months. With mean follow-up of 8.3±1.9 years, Sjögren & Thulin (2004) found long-term postoperative QOL to be comparable to that of an age-matched population. In addition, Huber et al. (2007) showed that 97% of the survivors lived in their own homes. Finally, 81% had no or few self-perceived restrictions in their daily activities (Kohl et al., 2007), 93% felt much better after the operation and 81% of octogenarians had few disabilities in daily activities (Huber et al., 2007). Also, QOL was not affected by the constraints entailed by treatment(s) associated with the type of prosthesis. Indeed, after postoperative month 3, >90% who had received a bioprosthesis were in sinus rhythm and were taking only low-dose aspirin. Vicchio et al. (2008) compared the QOL of 62 octogenarians with bioprosthetic valves vs 98 with mechanical valves during a mean follow-up of 3.4 ± 2.8 years and found that the prosthesis

However, all those studies had some limitations. Indeed, all of them were retrospective except for Olsson et al. (1996). Only those by Asimakopoulos et al. (1997) and Stoica et al. (2007), representing UK registry results, were multicenter investigations. Very few studies specifically and exclusively evaluated the outcomes of isolated AVR for SAS (Asimakopoulos et al., 1997; Leonteyv et al., 2009; Thourani et al., 2008). Some studies mixed AVR with CABG or other operations, whereas others mixed AVR for SAS or severe aortic insufficiency (i.e., Stoica et al., 2006; Sundt et al., 2000). The sample sizes also varied widely from one study to another: ranging from 24 (Bashour et al., 1990) to 1100 patients (Asimakopoulos et al., 1997). Lastly, those studies retrospectively covered long periods, lasting 5 (Sundt et al.,

Those results must be interpreted carefully, keeping in mind that octogenarians with SAS referred to a surgeon are highly selected, as that decision-making is complex. Bouma et al. (1999) showed that only 59% of the patients who should have had an AVR according to international guidelines (Bonow et al., 2006) were actually offered surgical treatment. They were mainly symptomatic, >80 years old and had high transaortic valve gradients. On the other hand, Iung et al. (2005) observed that a decision not to operate was made for 33% of SAS patients. Multivariate analyses retained left ventricular ejection fraction and age (OR 1.84 for 80–85 year olds, OR = 3.38 for those ≥85 years) as being significantly and independently associated with the decision not to operate. Neurological dysfunction was the only comorbidity associated with that decision. During 2007, Freed et al. (2007) retrospectively studied the outcomes of SAS patients referred to their echocardiography laboratory. Among the 106 SAS patients, only 31% underwent surgery. The most common reasons symptomatic SAS patients did not undergo AVR were: their symptoms were thought to be unrelated to AS, too high surgical risk and/or patients refused (Freed et al.,

type had no impact on their QOL.

**2.9 Limitations of those studies** 

2000) to 16 years (Elayda et al., 1993).

**2.10 Decision-making** 

2010).

Concerning the intermediate-term prognosis, crude results were good (Table 3), particularly compared with the natural course of SAS (Schwarz et al., 1982). At 5 years, survival ranged from 52% (Florath et al., 2010) to 82% (Stoica et al., 2006) for populations whose mean age at surgery was 83 years. Some authors reported a 30% 10-year survival rate with a Kaplan– Meier median-survival estimate of 7.4 years (Thourani et al., 2008). Many studies also showed that, compared to an age- and sex-matched population, prognoses were comparable in different western countries: France (Maillet et al., 2009) and Sweden (Sjögren & Thulin, 2004). Stoica et al. (2006) found that the standardized mortality ratio (observed postAVR mortality/observed mortality for matched population) was 45.6% in favor of the surgical population in the UK, with 5-year survival rates of 82.1% for the surgical group versus 55.9% for a general population with the same age–sex distribution (p<0.001). The most common causes of late death were dominated by malignancy (20.5%), non-valve related cardiac failure (18.5%), valve-related stroke (18%) and pneumonia (11%) in a cohort of 1100 elderly patients included in the UK Heart Valve Registry. It must be kept in mind that onethird of the patients with malignancy died within 18 months after cardiac surgery. That observation emphasizes the improved preoperative cancer screening of elderly patients before AVR (Asimakopoulos et al., 1997).


AVR = aortic valve replacement; I AVR = isolated AVR; NR = not reported.

Table 3. Intermediate-term AVR outcomes of octogenarians

#### **2.8 Impact of AVR on QOL among octogenarians**

Improving QOL is one of the most important aims of AVR especially for octogenarians. Authors of retrospective studies concluded that QOL was good after AVR at intermediate term but, in many studies, preoperative QOL had not been evaluated (Maillet et al., 2009; Sundt et al., 2000). Using the medical outcomes study Short Form-36 (SF-36), Sundt et al. (2000) showed that the QOL of a surgical population with a mean age of 84 years was

Concerning the intermediate-term prognosis, crude results were good (Table 3), particularly compared with the natural course of SAS (Schwarz et al., 1982). At 5 years, survival ranged from 52% (Florath et al., 2010) to 82% (Stoica et al., 2006) for populations whose mean age at surgery was 83 years. Some authors reported a 30% 10-year survival rate with a Kaplan– Meier median-survival estimate of 7.4 years (Thourani et al., 2008). Many studies also showed that, compared to an age- and sex-matched population, prognoses were comparable in different western countries: France (Maillet et al., 2009) and Sweden (Sjögren & Thulin, 2004). Stoica et al. (2006) found that the standardized mortality ratio (observed postAVR mortality/observed mortality for matched population) was 45.6% in favor of the surgical population in the UK, with 5-year survival rates of 82.1% for the surgical group versus 55.9% for a general population with the same age–sex distribution (p<0.001). The most common causes of late death were dominated by malignancy (20.5%), non-valve related cardiac failure (18.5%), valve-related stroke (18%) and pneumonia (11%) in a cohort of 1100 elderly patients included in the UK Heart Valve Registry. It must be kept in mind that onethird of the patients with malignancy died within 18 months after cardiac surgery. That observation emphasizes the improved preoperative cancer screening of elderly patients

First Author Year N Study I Age at Survival at

1975–1991 1982–1992 1986–1995 1993–1998 1992–2003 1990–1993 1993–2003 1996–2003 1999–2003 1992–2004 1993–2005 1996–2006 1995–2006 1996–2006

AVR = aortic valve replacement; I AVR = isolated AVR; NR = not reported.

Table 3. Intermediate-term AVR outcomes of octogenarians

**2.8 Impact of AVR on QOL among octogenarians** 

period AVR surgery 1

45% 42% 100% 33.1% 62.1% NR 74% 27.2% 25% 76% 57% 100% 100% 51%

Improving QOL is one of the most important aims of AVR especially for octogenarians. Authors of retrospective studies concluded that QOL was good after AVR at intermediate term but, in many studies, preoperative QOL had not been evaluated (Maillet et al., 2009; Sundt et al., 2000). Using the medical outcomes study Short Form-36 (SF-36), Sundt et al. (2000) showed that the QOL of a surgical population with a mean age of 84 years was

year

90.8% 82% 89% 80% 86.4% 92.3% 84% 83.7% 94% 85.5% 82% 87% 81% 82%

3 years

84.2%

94% 80.8% 70% 68.2% 71%

5 years

76% 62% 69% 55% 69.4% 65% 56% 82.1% 75% 73.2% 56% 61% 57% 52%

8 years

45.8%

30%

before AVR (Asimakopoulos et al., 1997).

Elayda Tsai

Sundt Chiappini Sjögren Collart Stoica Huber Kolh Melby Thourani Leontyev Florath

Asimakopoulos

comparable to that predicted for the general population >75 years old. Olsson et al. (1996), prospectively compared QOL evolution for 2 groups of patients referred for isolated AVR; 30 octogenarians vs 30 patients 65–75 years old. At 1-year postAVR, octogenarians, despite their more compromised preoperative status, had markedly regressed symptoms, and their physical abilities and general well-being were of a similar magnitude to those of the younger patients. Those improvements appeared as of 3 months. With mean follow-up of 8.3±1.9 years, Sjögren & Thulin (2004) found long-term postoperative QOL to be comparable to that of an age-matched population. In addition, Huber et al. (2007) showed that 97% of the survivors lived in their own homes. Finally, 81% had no or few self-perceived restrictions in their daily activities (Kohl et al., 2007), 93% felt much better after the operation and 81% of octogenarians had few disabilities in daily activities (Huber et al., 2007). Also, QOL was not affected by the constraints entailed by treatment(s) associated with the type of prosthesis. Indeed, after postoperative month 3, >90% who had received a bioprosthesis were in sinus rhythm and were taking only low-dose aspirin. Vicchio et al. (2008) compared the QOL of 62 octogenarians with bioprosthetic valves vs 98 with mechanical valves during a mean follow-up of 3.4 ± 2.8 years and found that the prosthesis type had no impact on their QOL.

#### **2.9 Limitations of those studies**

However, all those studies had some limitations. Indeed, all of them were retrospective except for Olsson et al. (1996). Only those by Asimakopoulos et al. (1997) and Stoica et al. (2007), representing UK registry results, were multicenter investigations. Very few studies specifically and exclusively evaluated the outcomes of isolated AVR for SAS (Asimakopoulos et al., 1997; Leonteyv et al., 2009; Thourani et al., 2008). Some studies mixed AVR with CABG or other operations, whereas others mixed AVR for SAS or severe aortic insufficiency (i.e., Stoica et al., 2006; Sundt et al., 2000). The sample sizes also varied widely from one study to another: ranging from 24 (Bashour et al., 1990) to 1100 patients (Asimakopoulos et al., 1997). Lastly, those studies retrospectively covered long periods, lasting 5 (Sundt et al., 2000) to 16 years (Elayda et al., 1993).

#### **2.10 Decision-making**

Those results must be interpreted carefully, keeping in mind that octogenarians with SAS referred to a surgeon are highly selected, as that decision-making is complex. Bouma et al. (1999) showed that only 59% of the patients who should have had an AVR according to international guidelines (Bonow et al., 2006) were actually offered surgical treatment. They were mainly symptomatic, >80 years old and had high transaortic valve gradients. On the other hand, Iung et al. (2005) observed that a decision not to operate was made for 33% of SAS patients. Multivariate analyses retained left ventricular ejection fraction and age (OR 1.84 for 80–85 year olds, OR = 3.38 for those ≥85 years) as being significantly and independently associated with the decision not to operate. Neurological dysfunction was the only comorbidity associated with that decision. During 2007, Freed et al. (2007) retrospectively studied the outcomes of SAS patients referred to their echocardiography laboratory. Among the 106 SAS patients, only 31% underwent surgery. The most common reasons symptomatic SAS patients did not undergo AVR were: their symptoms were thought to be unrelated to AS, too high surgical risk and/or patients refused (Freed et al., 2010).

Relationship Between Aortic Valve Replacement and Old Age 175

improved physical and mental component summary scores from 28.4±10 to 46.8±9.2

The results of all studies demonstrated that TAVI can be implanted safely, with intraprocedural mortality now a mean of 1% (Webb et al., 2009; Tamburino et al., 2011). Implantation failure is becoming rare, with the successful implantation rate ≥98% in the most recent studies (Bleiziffer et al., 2009; Tamburino et al., 2011). Changing the surgical

Coronary obstruction rarely complicates valve implantation (<1%). Valve positioning is challenging, particularly when the distance between the annulus and the coronary artery is short, as the native valve may be pushed against the coronary ostium (Lefèvre et al., 2011). Some complications seem to be related to the access route used. With TF access, major vascular complications occur in 6.8–11.7% of the cases (Bleiziffer et al., 2009; Webb et al., 2009). However, technological advances have permitted sheath-size reduction from 24F to 18F, thereby allowing a percutaneous procedure with locoregional anesthesia and fewer vascular injuries. Improved screening, case selection and experience should surely lower the

Second, 10% of the patients suffer clinical strokes (Grube et al. 2007). In a recent diffusionweighted, magnetic resonance imaging study on TAVI patients, the risk of diffuse cerebral embolism was 72.7%, with patients frequently having multiple new but clinically silent brain lesions. Although cerebral embolism was extremely common in the TF-TAVI cohort, the clinical stroke rate was 3.6% (Ghanem et al., 2010). It was suggested that TA-TAVI might be associated with fewer cerebral embolic events. However, results are controversial and further studies with larger cohorts are needed. Two mechanisms are involved: aortic atheroemboli and valvular calcific emboli. The elderly are at particularly high risk for perioperative neurological events because of advanced cerebral ischemic disease present

For both accesses, annulus measurement is challenging. Indeed, no gold standard currently exists for aortic annular measurement but transesophageal echocardiography provides accurate data to guide valve sizing before implantation (Messika-Zeitoun et al., 2010). Paravalvular aortic regurgitation is common after TAVI but remains stable at late follow-up (Webb et al., 2009). In the PARTNER study, moderate-or-severe perivalvular leakage was present in 11.8% of the patients at 30 days and 10.5% at 1 year (Leon et al., 2010). However, postprocedural paravalvular aortic regurgitation ≥2+ (HR 3.79) mainly affected later

Conduction abnormalities are frequent after TAVI (Roten et al., 2010). The occurrence of atrioventricular block requiring pacemaker insertion at 30 days seems lower with the Edwards SAPIEN™ (<5%) (Lefèvre et al., 2011) than the CoreValve™ (up to 30%) (Jilaihawi et al., 2009). One possible explanation could be that the CoreValve™ was designed to be seated lower than the SAPIEN™ valve and might compress the underlying conduction system. However, based on a cohort of 67 patients (41 received CoreValve™ and 26 SAPIEN™), Roten et al. showed that the sole independent risk factor for complete atrioventricular block after TAVI was preexisting right bundle branch block (Roten et al., 2010). Because prosthesis sizing is a critical issue, to avoid perivalvular leakage and valve migration, "over sizing" of TAVI might have increased the risk of atrioventricular block

(p<0.001) and from 37.3±10.8 to 50.6±10.1 (p<0.001), respectively.

approach during the intervention has also become very rare.

outcomes between 30 days and 1 year (Tamburino et al., 2011).

(Bleiziffer et al., 2009). Further investigations are mandatory.

**3.2 Specific TAVI-related complications** 

vascular injury rate further.

preoperatively (Wang et al., 2010).
