Clinical outcome and quality of life in octogenarians following transcatheter aortic valve implantation (TAVI) for symptomatic aortic stenosis

International Journal of Cardiology 168 (2013) 281–286

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Clinical outcome and quality of life in octogenarians following transcatheter aortic valve implantation (TAVI) for symptomatic aortic stenosis Antonio Grimaldi a,⁎, Filippo Figini a, Francesco Maisano a, Matteo Montorfano a, Alaide Chieffo a, Azeem Latib a, Federico Pappalardo a, Pietro Spagnolo b, Micaela Cioni a, Anna Chiara Vermi a, Santo Ferrarello a, Daniela Piraino a, Valeria Cammalleri a, Enrico Ammirati a, Francesco Maria Sacco a, Iryna Arendar a, Egidio Collu a, Giovanni La Canna a, Ottavio Alfieri a, Antonio Colombo a a b

Cardiovascular and Thoracic Department, San Raffaele Scientific Institute and Università Vita-Salute, Milan, Italy Cardiovascular Prevention Centre, San Raffaele Scientific Institute and Università Vita-Salute, Milan, Italy

a r t i c l e

i n f o

Article history: Received 30 September 2011 Received in revised form 14 May 2012 Accepted 15 September 2012 Available online 10 November 2012 Keywords: TAVI Aortic stenosis Quality of life

a b s t r a c t Objective: TAVI is the alternative option in pts with AS deemed ineligible for surgery. Although mortality and morbidity are measures to assess the effectiveness of treatments, quality of life (QOL) should be an additional target. We assessed clinical outcome and QOL in octogenarians following TAVI. Design: All octogenarians with a risk profile considered by the Heart Team to be unacceptable for surgery entered in this registry. QOL was assessed by questionnaires concerning physical and psychic performance. Patients: A hundred forty-five octogenarians (age: 84.7 ± 3.4 years; male: 48.3%) underwent TAVI for AS (97.2%) or isolated AR (2.8%). NYHA class: 2.8 ± 0.6; Logistic EuroScore: 26.1 ± 16.7; STS score: 9.2 ± 7.7.Echocardiographic assessments included AVA (0.77 ± 0.21 cm2), mean/peak gradients (54.5 ± 12.2/ 88 ± 19.5 mmHg), LVEF (21% = EF ≤ 40%), sPAP (43.1 ± 11.6 mmHg). Interventions: All pts underwent successful TAVI using Edward-SAPIEN valve (71.2%) or Medtronic CoreValve (28.8%). Main outcome measures: Rates of mortality at 30 days, 6 months and 1 year were 2.8%, 11.2% and 17.5%. Results: At 16-month follow up, 85.5% survived showing improved NYHA class (2.8 ± 0.6 vs 1.5 ± 0.7; p b 0.001), decreased sPAP (43.1 ± 11.6 mmHg vs 37.1 ± 7.7 mmHg; p b 0.001) and increased LVEF in those with EF ≤ 40% (34.9 ± 6% vs 43.5 ± 14.4%; p = 0.006). Concerning QOL, 49% walked unassisted, 79% (39.5% among pts ≥ 85 years) reported self-awareness improvement; QOL was reported as “good” in 58% (31.4% among pts ≥85 years), “acceptable according to age” in 34% (16% among pts ≥85 years) and “bad” in 8%. Conclusion: TAVI procedures improve clinical outcome and subjective health-related QOL in very elderly patients with symptomatic AS. © 2012 Elsevier Ireland Ltd. All rights reserved.

1. Introduction Changing clinical epidemiology in patients with valvular heart disease have brought challenges for cardiologists and cardiac surgeons alike. The definition of ‘elderly’ population in the cardiology literature has evolved: initially >70 years, then >75 years [1], now > 80 years of age. Life expectancy and quality of life (QOL) of the elderly continue to expand at the cost of an increasing prevalence of cardiovascular conditions [2–5]. Aortic stenosis (AS) is the most common form of valvular heart disease predominatly affecting the elderly (wich are very often high risk candidates for surgical aortic valve replacement (AVR), still considered as the gold standard treatment [6,7]. The alternatives

⁎ Corresponding author. Tel.: +39 0226437124. E-mail address: [email protected] (A. Grimaldi). 0167-5273/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2012.09.079

percutaneous approaches to the management of symptomatic AS in high-risk patients have become more attractive and raised profound interest in recent years. The superiority of transcatheter aortic valve implantation (TAVI) compared with medical therapy for patients deemed unfit for surgery has been recently established by the “Placement of AoRTic TraNscathetER Valve” (PARTNER) Trial [8] and preliminary randomized data in high-risk patients have confirmed that TAVI is non-inferior to AVR in terms of a safety and effectiveness [9]. This finding will probably lead to an exponential increase in TAVI procedures over the next decade. Although mortality and morbidity are typical outcome measures used to assess the effectiveness of various treatments, QOL should be an additional target and a major expectation for this elderly patient's profile [10–12]. Purpose of the study was therefore to assess clinical outcomes of octogenarians following TAVI procedure, with a special emphasis on symptoms, echocardiographic assessment and QOL of very elderly patients (included those ≥ 85 years).

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2. Material and methods All octogenarians with a risk profile considered by the Heart Team to be unacceptable for surgery entered in this prospective registry. 2.1. Patient evaluation All the patients have been evaluated by a multidisciplinary heart team. Pre-procedural screening included standard transthoracic and/or transesophageal echocardiography, multislice computed tomography (MSCT), and if required, coronary angiography. Transthoracic echocardiography was performed at 24 to 48 h post-procedure and during clinical follow up at 1, 6 and 12 months, allowing to evaluate clinical improvement by reverse NYHA class and to assess prosthesis performance and left ventricular (LV) function. The indication for TAVI was based on symptomatic severe AS [aortic valve area (AVA) b1 cm2 or mean gradient >40 mmHg] and high surgical risk profile defined as a logistic European System for Cardiac Operative Risk Evaluation (logistic-EuroSCORE) ≥10% or Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) ≥10% or by associated co-morbidities not captured by the two scores (e.g. prior thoracic radiotherapy, porcelain aorta, liver cirrhosis, marked patient frailty) [13,14]. Some patients affected by symptomatic isolated grade 4 AR entered in the registry. The suitability for the transfemoral approach was determined by evaluating the ilio-femoral artery diameters on MSCT. †All patients provided written informed consent for the procedures and subsequent data collection and analysis for research purposes. The devices currently available were the ballon-expandable Edwards Sapien (USA) and Sapien XT (Edwards Lifesciences Inc, Irvine, CA, USA) and the self-expandable CoreValve Revalving System (Medtronic, Medtronic Inc, Minneapolis MN). 2.2. Quality of life Post-TAVI QOL was assessed by a tailored questionnaire based on living conditions, physical status, walking capacity, perception of daily activity and psychic performance status (Table 1). Data were obtained from patients or family during the follow up visit or through further phone contact. Living conditions were classified as patient living “at home or in an institution” and general status as patient having or not “diffuse bodily pain”; physical performance status was defined by perception of daily activity (heavy, moderate or light) and by walking capacity, classified as patient “confined to a wheelchair”, or “able to walk unassisted ≥ 500 mt/per day”, or “walking with trouble” (assisted, with sticks or walking frame). Psychic performance status was defined as patient being “satisfied”, “not satisfied” or not being influenced by TAVI procedure. As a whole, QOL was classified as “good”, as “acceptable according to age” or “bad”. Being retrospective, the analysis of QOL was only descriptive; hence, no statistical test was performed.

3. Results Clinical and echocardiographic characteristics of population entered in the study are summarized in Table 2. A hundred forty-five prospectively studied octogenarians (mean age: 84.7±3.4 years; male: 70 pts, 48.3%) undergone successful TAVI procedure for severe AS (141 pts; Table 1 Questionnaire concerning quality of life (QOL) following TAVI procedure in the population study. QOL Lifestyle At home In a nursery Physical status Diffuse bodily pain No bodily pain Perception of daily activity Heavy Moderate Light Walking capacity On a weelchair Walking with trouble Walking unassisted ≥ 500 m/per day Psychic performance status Satisfied Not satisfied No change QOL as a whole Good Acceptable according to age Bad

97.2%) (AVA: 0.77±0.21 cm2; mean gradient: 54.5±12.2 mmHg; peak gradient: 88±19.5 mmHg) or isolated grade 4 AR (4 pts; 2.8%). All patients were symptomatic (NYHA class: 2.8±0.6) and deemed unfit for conventional AVR according to advanced age and other risk factors (Logistic EuroSCORE: 26.1±16.7; STS score: 9.2±7.74). Pre-TAVI echocardiography included assessments of LV systolic function (20.1%, 30 pts with EF≤40%) and of systolic pulmonary arterial pressure (sPAP) (43.1±11.6 mmHg). All patients underwent successful TAVI procedure using both systems devices, Edwards-SAPIEN valve (ESV) (63.5%) and Medtronic CoreValve (MCV) (35.9%) delivered by different approaches: transfemoral (83.4%), transaxillary (7.6%), transapical (8.3%) and transaortic (0.7%). 4. Outcomes Clinical outcomes and echocardiographic endpoints are shown in Table 3. Rates of mortality at 30 days, 6 months and 1 year were respectively 2.8% (4/145 pts), 11.2% (13/116 pts) and 17.5% (14/80 pts) (Fig. 1). With a median follow-up of 13.5± 10 months, survival rate was 85.5% (124 pts) (Fig. 2); the median follow-up for patients able to attend the visit and answer QOL questionnaires was 16± 10 months. All patients referred improvement of clinical symptoms (NYHA baseline 2.8 ±0.6 vs after 1.5 ± 0.7; p b 0.001) showing significant decrease of sPAP (baseline 43.1± 11.6 mmHg vs after 37.1 ± 7.7 mmHg; p b 0.001) and increase of LVEF in those with EF ≤40% (baseline 34.9± 6.1% vs after 43.5 ± 14.4%; p = 0.006). 5. Quality of life Results from QOL questionnaires are shown in Table 4. Among the overall population, 99% of patients lived at home, 80.7 did not complain bodily pain, 65.3% described moderate daily fatigue, 47% walked with sticks and 49% walked unassisted. Concerning the psychic performance

Table 2 Clinical and echocardiographic characteristics of population study. Variable

Mean ± SD (%)

N Age (years) Gender distribution (M) NYHA class Logistic Euroscore STS score Indication for TAVI AS AR AVA (cm2) Aortic PG (mmHg) Mean Max EF (%) ≤40 (30 pts) sPAP (mmHg) Procedural approach Transfemoral Transaxillary Transapical Transaortic Device system Corevalve (MCV) Edwards SAPIEN (ESV) Valve size 23 26 29

145 84.7 ± 3.4 70 (48.3) 2.8 ± 0.58 26.1 ± 16.7 9.2 ± 7.74 141 (97.2) 4 (2.8) 0.77 ± 0.21 54.5 ± 12.2 88.14 ± 19.55 52.4 ± 11.5 34.9 ± 6.1 43.4 ± 11.7 121 (83.4) 11 (7.6) 12 (8.3) 1 (0.7) 52 (35.9) 93 (63.5) 39 (26.9) 74 (51) 32 (22.1)

Values are expressed as mean ± standard deviation. NYHA, New York Heart Association; STS, Society of Thoracic Surgeons; AS, aortic stenosis; AR, aortic regurgitation; AVA, aortic valve area; EF, ejection fraction; sPAP, systolic pulmonary arterial pressure. MCV, Medtronic CoreValve; ESV, Edwards-SAPIEN valve.

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Table 3 Clinical outcome and echocardiographic endpoints in the overall population. Variable

Mean ± SD N (%)

Population Study Total deaths at follow-up Mortality rates at follow-up 30 days 6 months 1 year Leading causes of death Sudden death Arrhythmic storm CHF following iatrogenic VSD Aortic rupture (in-hospital) Cancer Non cardiogenic respiratory failure Intracranial bleeding Ischemic stroke Other Unknown NYHA class

145 21/145 (14.5)

Echocardiographic Endpoints EF (%) >40 ≤40 sPAP (mmHg)

4/145 (2.8) 13/116 (11.2) 14/80 (17.5) 21 3 1 1 2 3 2 2 1 3 3 Pre-TAVI Post-TAVI 2.8 ± 0.6 1.5 ± 0.7 Pre-TAVI Post-TAVI

P value b0.001⁎ P value

53.3 ± 10.6 34.9 ± 6.1 43.1 ± 11.6

n.s. 0.006⁎ b0.001⁎

53 ± 10.6 43.5 ± 14.4 37.1 ± 7.7

Values are expressed as mean ± standard deviation. CHF, congestive heart failure; VSD, ventricular septal defect; NYHA, New York Heart Association; EF, ejection fraction; sPAP, systolic pulmonary arterial pressure. ⁎ p b 0.01.

Fig. 2. Survival rate in the overall population following TAVI procedure.

No significant correlation was found between the procedural complications of TAVI (VARC criteria) and the clinical parameters describing the QOL outcomes in the population study (Table 5). status following TAVI, 79% of patients (39.5% among pts ≥85 years) referred self-awareness improvement (Fig. 3); as a whole, QOL was referred to be “good” by 72 pts (58% among overall population; 31.4% among pts ≥85 years), “acceptable according to age” by 42 pts (34% among overall population; 16% among pts ≥85 years) and “bad” by 10 pts (8% of overall population; 3.2% among pts ≥85 years) (Fig. 4).

6. Discussion Since there is no effective conservative treatment for symptomatic severe AS, TAVI has become an appropriate alternative for elderly

Fig. 1. Mortality rates in the overall population following TAVI procedure.

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Table 4 Quality of life following TAVI procedure in the population study. VARIABLE

N (%)

Lifestyle At home In a nursery Physical status Diffuse bodily pain No bodily pain Walking capacity On a wheelchair Walking with trouble Walking unassisted ≥ 500 m/per day Perception of daily activity Heavy Moderate Light

Psychic performance status Satisfied Not satisfied Unchanged QOL as a whole Good Acceptable according to age Bad

(99) (1) 24 (19.3) 100 (80.7) 5 (4) 58 (46.8) 61 (49.2) 22 (17.7) 81 (65.3) 21 (17) Overall population

Age ≥85 years

124 (100) 98 (79) 8 (6.5) 18 (14.5)

63 (50.8) 49 (39.5) 2 (1.6) 12 (9.7)

72 (58) 42 (34) 10 (8)

39 (31.5) 20 (16.1) 4 (3.2)

patients with very high surgical risk [14]. At the time patients are referred for intervention, they present reduced life expectancy and severe heart failure symptoms with consequent restrictions in the normal daily living. In our report TAVI shows a favourable clinical outcome at mid-term follow-up in very elderly patients, reporting a rate of death from any cause of 2.8% at 30-days, 11.2% at 6 months and 17.5 at 1-year follow up (Fig. 1). These results reflect proper patients selection and improved procedural learning curve including transfemoral and other approaches in agreement with previous reports [15].

6.1. QOL assessment Previous studies have showed clinical benefit in terms of quality of life in the first months [10] after TAVI but midterm follow-up QOL results are scarce [16].

Clinical findings and referred improvements of QOL qualitatively reflect the good results of TAVI in the elderly. Currenty, advanced age is other than an obsolete concern in terms of health-related quality of life [17–21]. Mean age is rising in western countries and the perception of disease and discomforts may be totally different in the elderly compared to the youngs. Young patients do not easily accept body discomforts and nothwithstanding a prompt physical recovery following invasive treaments, they might pass through a depressive status and be concerned about disease recurrence during a long expectancy of life; old patients do not reveal the same fast-track recovery and may experience more periprocedural complications related to the different biological status. But interestingly, the trend of psychic recovery may be peculiar: octagenarians may experience a new trend of life, if body discomfort diseappear. As a consequence, elderly patients might consider their overall QOL as good (58% of overall population; 31.4% among pts ≥85 years (Fig. 4), whereas the family will define it as just acceptable, being the perception totally different according to the expectancy of life. On the other hand, elderly patients may be totally refractary (8% of overall population; 3.2% among pts ≥85 years (Fig. 3) to psychic improvement depending on chronic morbidity affecting the mood and/or self-awareness (e.g. cancer, long-term oxygen therapy, cognitive impairment or recent widowood). Walking capacity might not necessarily be a major issue affecting QOL as a whole since also patients confined “on a weelchair” (5 pts, 34.5%) considered their current QOL as “acceptable according to age” (4 pts, 80%) once TAVI procedure has removed dyspnea and severe fatigue allowing them to perform the daily activities on the same weelchair. This condition would probably mean that for elderly patients the perception of disease and recovery should be addressed toward different targets such as improved self–awareness and routine daily activity [18]. The feeling that patient's quality of life should be measured in clinical practice has led to the development of a wide range of questionnaires [17,22] but most of them might be difficult to assess in the clinical setting of very elderly patients with symptomatic aortic stenosis and high risk comorbidities. In our population advanced age (50% of pts were ≥ 85 years) plus critical status (80.3% of pts ≥ 85 years were in NYHA III–IV) made the pre-procedural QOL assessment very difficult to get at admission to hospital. At follow-up, the analysis was retrospective and descriptive and no comparison was performed to test a statistical QOL improvement between pre- and post-TAVI assessments as reported by other studies [10,11,21]. Nevertheless, we can assume

Fig. 3. Quality of life in the overall population and in pts ≥85 years of age.

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Fig. 4. Psychic performance status following TAVI procedure and in pts ≥85 years of age.

Table 5 Correlation between procedural complications of TAVI (VARC definition) and quality of life in the population study. Procedural complications

Cardiovascular events

Bleeding Life-threatening or major

AKI/stage 3

MVC

CSE

PM implantation

Events

Walking capacity n (%)

Perception of activity n (%)

Mental performance n (%)

QOL n (%)

0 = no 1 = yes 0 = 122 1=2 p = NS 0 = 46 1 = 78 p = NS 0 = 117 1=7 p = NS 0 = 104 1 = 20 p = NS 0 = 46 1 = 77 *p = 0.04 0 = 109 1 = 15 p = NS

1

2

3

1

2

3

1

2

3

1

2

3

5(4) 0

57(47) 1(50)

60(49) 1(50)

22(18) 0

79(65) 2(100)

21(17) 0

97(79) 1(50)

8(7) 0

17(14) 1(50)

70(57) 2(100)

42(34) 0

10(8) 0

1(2) 4(5)

23(50) 35(45)

22(48) 39(50)

9(20) 13(17)

31(64) 50(64)

6(13) 15(19)

38(83) 60(77)

0 8(10)

8(19) 10(3)

28(61) 44(56)

15(33) 27(35)

3(6) 7(9)

5(4) 0

54(46) 4(57)

58(50) 3(43)

21(18) 1(14)

75(64) 6(86)

21(18) 0

92(78) 6(86)

8(7) 0

17(14) 1(14)

66(56) 6(86)

41(35) 1(14)

10(9) 0

5(5) 0

49(47) 9(45)

50(48) 11(55)

20(19) 2(10)

67(64) 14(70)

17(63) 4(20)

81(78) 17(85)

6(6) 2(10)

17(16) 1(5)

60(58) 12(60)

36(35) 6(30)

8(8) 2(10)

2(4) 3(4)

24(52) 33(43)

20(44) 41(53)

5(11) 17(22)

35(76) 45(58)

6(13) 15(20)

41(89) 56(72)

3(7) 5(7)

2(4)* 16(21)*

27(59) 45(59)

15(33) 26(34)

4(9) 6(8)

4(4) 1(7)

51(47) 7(47)

54(50) 7(47)

19(17) 3(20)

71(65) 10(67)

19(17) 2(13)

87(80) 11(73)

5(5) 3(20)

17(16) 1(7)

65(60) 7(47)

35(32) 7(47)

9(8) 1(7)

QOL: Quality of life; AKI: Acute Kidney Injury; MVC: Major vascular complications; CSE: Combined Safety Endpoint (30 dd) according to VARC definitions. 1,2,3 = grading of QOL's parameters (see Table 4).

that physical and psychic performance status were both relevant markers of improved QOL in the population study since no significant association was found between the complications of TAVI procedure according to the VARC definition [23] and the clinical parameters affecting the QOL outcomes (Table 5).

7. Conclusions and limits TAVI procedures provides significant improvements in terms of clinical outcome and subjective health-related quality of life also in very elderly patients with symptomatic AS. Impressive improvement in physical and psychological dimensions was noted at 16-month follow-up and most of patients were living independently and referred self-awareness improvement, reaffirming their decision to have TAVI. As a limit of the study, according to the advanced age and population's morbidity, the post-TAVI analysis was only descriptive and further prospective studies will be necessary to test the real clinical predictors of QOL improvement

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