Abstract

Aims

We assessed the impact of transcatheter aortic valve implantation (TAVI) on functional performance and quality of life (QoL) in a high-risk patient population with multiple comorbidities.

Methods and results

Between January 2009 and December 2014, 145 high-risk patients (EuroSCORE II 7.3% [4.9; 14.9]) with severe symptomatic aortic valve stenosis (AS) underwent TAVI in a single centre. We prospectively evaluated New York Heart Association (NYHA) functional class, 6-minute walking distance (6MWD), and QoL using the validated Dutch version of the EuroQol-5D (EQ-5D) descriptive assessment and a visual analogue scale (EQ-VAS) at baseline, 30 days, as well as 6, 12, and 24 months after TAVI. All patients were eligible for analysis. New York Heart Association functional class improved significantly at 30-day, 6-, 12-, and 24-month follow-up (P < 0.001 for all). The absolute 6MWD improved significantly at 30 days (+19.3 ± 8.2 m; P= 0.0499) and at 6 months (+23.3 ± 8.1 m; P = 0.0194). A favourable trend was maintained at 12 months (+17.1 ± 8.8 m; P = 0.1879), whereas at 24 months 6MWD was similar to baseline values. No significant change in the descriptive assessment of QoL (EQ5D) was observed, whereas the EQ-VAS showed a significant improvement in QoL up to 24 months (P < 0.0180 for all time-points).

Conclusion

In high-risk comorbid patients with symptomatic AS, TAVI results in a significant but temporary improvement of functional performance when assessed with objective measures of 6MWD but not of EQ-5D. Moreover, TAVI has a significant and sustained impact on subjective well-being and exercise capacity assessed with the EQ-VAS and NYHA score.

Introduction

Degenerative aortic valve stenosis is the most common valvular heart disorder in industrialized countries, with a prevalence rate of 4–5% in adults aged >65 years.1 Mortality is low but increases dramatically after onset of symptoms, and medical management is associated with a 1-year mortality rate of nearly 50%.2 Surgical aortic valve replacement is considered the ‘gold standard’, but nearly 30% of patients are rejected because of co-morbidities and associated high surgical risk.3–5 Transcatheter aortic valve implantation (TAVI) has become a valuable alternative therapeutic option in this particular patient population, with the objective to prolong life and improve functional status and quality of life (QoL). Functional performance and QoL are playing an increasing role in the health-economic assessment of novel expensive medical technologies such as TAVI, but these parameters are difficult to score in an ageing patient population with multiple comorbidities. Since the absolute survival benefit in this population may be less substantial, increasing the QoL becomes even more relevant. We performed a prospective evaluation of functional performance and QoL at baseline, 30 days, as well as 6, 12, and 24 months after TAVI, in an elderly patient population with multiple comorbidities, rejected for surgical aortic valve replacement (SAVR).

Methods

Patient population and procedural details

The study population consisted of all patients with symptomatic severe aortic stenosis (aortic valve area <1 cm2) undergoing TAVI at a single institution from January 2009 to December 2014. Indication for TAVI was based on rejection for SAVR for anatomical/technical reasons or extensive comorbidities as assessed by the heart team, including a cardiologist, cardiac surgeon, and a geriatrician. A surgical risk score was estimated using the Society of Thoracic Surgeons (STS) score, the logistic EuroSCORE, and the EuroSCORE II, and comorbidity was quantified using the Charlson comorbidity index.6–9 Pulmonary hypertension was diagnosed during right heart catheterization according to the 2015 ESC guidelines.10 Frailty was assessed during this multidisciplinary evaluation based on eyeballing and results from the geriatric assessment. All procedures were performed under general anaesthesia, using fluoroscopic guidance in a hybrid room. The same TAVI team, including an interventional cardiologist and a cardiac surgeon, performed all the procedures, using SAPIEN and SAPIEN XT valves (Edwards LifeSciences, Irvine, CA, USA). Transapical implantation was performed in patients without suitable femoral access, as assessed by computed tomography or angiography during diagnostic cardiac catheterization.

We prospectively evaluated New York Heart Association (NYHA) functional class, 6-minute walking distance (6MWD), and QoL before and after TAVI. The local ethics committee approved the protocol, and all patients provided written informed consent to enter the registry.

Exercise capacity and New York Heart Association functional class assessment

New York Heart Association class was assessed at baseline, 30 days, as well as 6, 12, and 24 months after TAVI, by one of the cardiologists within the TAVI team blinded to the results of the 6MWD and the QoL assessment.

The 6MWD was evaluated in a flat 50-m long hospital corridor with floor-markings every 10 m. Patients were asked to walk from side to side, covering as much ground as possible during a 6-min period, without running or jogging. Feedback on time progression was given and encouragement was standardized. Patients were allowed to stop and rest during the test, but were instructed to resume walking as soon as they were able to do so. Results were expressed in absolute distance (m) and as the percentage of predicted distance according to the Enright's formula.11

Quality-of-life assessment

Quality of life was evaluated with the validated Dutch version of the EuroQoL-5D (EQ-5D).12,13 This general health-related measure is based on a descriptive evaluation of five health domains (mobility, degree of self-care, activities of daily life, mental status, and presence of pain/discomfort; EQ-5D) and an additional visual analogue scale (EQ-VAS) recording an individual's rating for his current health-related QoL state (best imaginable health state = 100 and worst imaginable state = 0). Patients completed the questionnaire at baseline, 30 days, as well as 6, 12, and 24 months after TAVI, and were asked to score the five health domains on a scale of 1–3, with 1 indicating no problems and 3 indicating severe problems. This Dutch version of the EQ-5D assessment provides an index ranging from 1 (no problems in any of the five domains) to −0.33 (worst possible state in all five domains), reflecting a state of general health and QoL (Table 1).

Table 1

Parameters and tariff in the Dutch and British EuroQol-5D descriptive health assessmenta,b

 Dutch British 
Fixed correction factor for a state different than ‘11111’ −0.071 −0.081 
Additional correction factor for 
 Some problems with mobility −0.036 −0.069 
 Unable to walk −0.161 −0.314 
 Some problems with self-care −0.082 −0.104 
 Unable to provide self-care −0.152 −0.214 
 Some problems with usual activities −0.032 −0.036 
 Unable to perform usual activities −0.057 −0.094 
 Some pain or other complaints −0.086 −0.123 
 Severe pain or other complaints −0.329 −0.386 
 Some complaints of anxiety or depression −0.124 −0.071 
 Severe complaints of anxiety or depression −0.325 −0.236 
Additional correction for severe problems in ≥1 dimension −0.234 −0.269 
 Dutch British 
Fixed correction factor for a state different than ‘11111’ −0.071 −0.081 
Additional correction factor for 
 Some problems with mobility −0.036 −0.069 
 Unable to walk −0.161 −0.314 
 Some problems with self-care −0.082 −0.104 
 Unable to provide self-care −0.152 −0.214 
 Some problems with usual activities −0.032 −0.036 
 Unable to perform usual activities −0.057 −0.094 
 Some pain or other complaints −0.086 −0.123 
 Severe pain or other complaints −0.329 −0.386 
 Some complaints of anxiety or depression −0.124 −0.071 
 Severe complaints of anxiety or depression −0.325 −0.236 
Additional correction for severe problems in ≥1 dimension −0.234 −0.269 

EQ-5D, EuroQol-5D.

aEach evaluation of a healthcare state starts at the value of 1. If a patient indicates a problem in ≥1 of the dimensions of the EQ-5D assessment, a fixed correction of −0.071 is applied. Further corrections are applied depending on the result of each specific dimension. A final additional correction of −0.234 has to be applied if the patient indicates severe problems in ≥1 of the dimensions.

bThe EQ-5D assessment can describe 243 different healthcare states, with values ranging from −0.33 for condition ‘33333’ to 1 for condition ‘11111’.

Endpoints of functional performance (both NYHA class and 6MWD) and QoL were equally assessed in non-prespecified subgroups of patients stratified according to age (< vs. ≥80 years), baseline NYHA classification (class I–II vs. III–IV), and access route (transfemoral vs. transapical). A separate analysis depending on survival status at 24-month follow-up was equally performed.

Statistical analysis

Continuous variables are expressed as mean ± standard deviation or median and interquartile range [IQR] depending on variable distribution. Categorical data are presented by their observed frequencies and percentages. Changes from baseline to follow-up were assessed using a Wilcoxon signed-rank test. To account for mortality throughout the study, a longitudinal generalized estimating equation (GEE) model was used.14 The GEE model employed an unstructured variance–covariance matrix to model the correlations within patient. Furthermore, data missing for reasons other than death were imputed using multiple imputation techniques, using a total of 100 imputations.15

All tests were two-sided and assessed at a significance level of 5%. Due to the exploratory nature of the study, all P-values were adjusted for multiple testing using a stepwise Bonferroni correction. All analyses were performed using SAS software, Version 9.2 of the SAS System for Windows (SAS Institute, Inc., Cary, NC, USA).

Results

Between January 2009 and December 2014, 145 patients underwent TAVI. Clinical, haemodynamic, and procedural characteristics of the study population are reported in Table 2. Overall peri-operative risk for SAVR was high, as assessed with the STS score (7.2% [5.31; 9.71]), logistic EuroSCORE (25% [17.00; 34.54]), and EuroSCORE II (7.3% [4.88; 14.89]), as a consequence of advanced age (84 years [80; 87]) and multiple comorbidities [Charlson comorbidity index (3.0 [2.0; 4.0])]. Eighty-nine TAVI procedures were performed using a transfemoral access (61%), while a transapical approach was preferred in 56 patients (39%).

Table 2

Baseline characteristics and echocardiographic parameters of the patient population (N = 145)

Age (years), median [IQR] 84 [80; 87] 
Male sex, n (%) 74 (51) 
Valve Edwards Sapien/Sapien XT 
Transfemoral, n (%) 89 (61) 
Transapical, n (%) 56 (39) 
STS score, median [IQR] 7.2 [5.3; 9.7] 
EuroSCORE II, median [IQR] 7.3 [4.9; 14.9] 
Logistic EuroSCORE, median [IQR] 25 [17; 34.5] 
Charlson comorbidity index, median [IQR] 3 [2; 4] 
Haemoglobin (mg/dL), median [IQR] 11.9 [11.0; 12.9] 
NYHA class, n (%) 
 I–II 18 (12.4) 
 III–IV 127 (87.6) 
Coronary artery disease, n (%) 99 (68.3) 
Previous myocardial infarction, n (%) 32 (22.1) 
Previous intervention, n (%) 
 CABG 40 (27.6) 
 PCI 70 (48.3) 
 PTAV 19 (13.1) 
Cerebrovascular disease, n (%) 58 (40.0) 
Peripheral vascular disease, n (%) 54 (37.2) 
COPD, n (%) 
 Any 49 (33.8) 
 Class III–IV 26 (17.8) 
Creatinine >2 mg/dL, n (%) 18 (12.4) 
Atrial fibrillation, n (%) 50 (34.5) 
Permanent pacemaker, n (%) 19 (13.1) 
Pulmonary hypertension, n (%) 100 (69.0) 
Frailty, n (%) 32 (22.1) 
Extensively calcified aorta, n (%) 24 (16.6) 
Deleterious effects of chest wall irradiation, n (%) 11 (7.6) 
Echocardiographic findings 
 Aortic valve area (cm2), median [IQR] 0.7 [0.5; 0.8] 
 Mean aortic valve gradient (mmHg), median [IQR] 48 [38; 59] 
 Mean LVEF (%), median [IQR] 55 [45; 60] 
Age (years), median [IQR] 84 [80; 87] 
Male sex, n (%) 74 (51) 
Valve Edwards Sapien/Sapien XT 
Transfemoral, n (%) 89 (61) 
Transapical, n (%) 56 (39) 
STS score, median [IQR] 7.2 [5.3; 9.7] 
EuroSCORE II, median [IQR] 7.3 [4.9; 14.9] 
Logistic EuroSCORE, median [IQR] 25 [17; 34.5] 
Charlson comorbidity index, median [IQR] 3 [2; 4] 
Haemoglobin (mg/dL), median [IQR] 11.9 [11.0; 12.9] 
NYHA class, n (%) 
 I–II 18 (12.4) 
 III–IV 127 (87.6) 
Coronary artery disease, n (%) 99 (68.3) 
Previous myocardial infarction, n (%) 32 (22.1) 
Previous intervention, n (%) 
 CABG 40 (27.6) 
 PCI 70 (48.3) 
 PTAV 19 (13.1) 
Cerebrovascular disease, n (%) 58 (40.0) 
Peripheral vascular disease, n (%) 54 (37.2) 
COPD, n (%) 
 Any 49 (33.8) 
 Class III–IV 26 (17.8) 
Creatinine >2 mg/dL, n (%) 18 (12.4) 
Atrial fibrillation, n (%) 50 (34.5) 
Permanent pacemaker, n (%) 19 (13.1) 
Pulmonary hypertension, n (%) 100 (69.0) 
Frailty, n (%) 32 (22.1) 
Extensively calcified aorta, n (%) 24 (16.6) 
Deleterious effects of chest wall irradiation, n (%) 11 (7.6) 
Echocardiographic findings 
 Aortic valve area (cm2), median [IQR] 0.7 [0.5; 0.8] 
 Mean aortic valve gradient (mmHg), median [IQR] 48 [38; 59] 
 Mean LVEF (%), median [IQR] 55 [45; 60] 

STS, Society of Thoracic Surgeons; IQR, interquartile range; NYHA, New York Heart Association; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; PTAV, percutaneous transluminal aortic valvuloplasty; COPD, chronic obstructive pulmonary disease; LVEF, left ventricular ejection fraction.

All-cause mortality rate was 6.2% (n = 9) at 30 days, 11.9% (n = 16) at 6 months, 21% (n = 26) at 12 months, and 37.9% (n = 36) at 24 months (Table 3). Half of the patients died from non-cardiovascular causes.

Table 3

Study compliance and overall survival

 Baseline 30 days 6 months 12 months 24 months 
Number of patients available for follow-up at the prespecified time interval 145 145 135 124 95 
Number of patients surviving 145 (100%) 136 (93.8%) 119 (88.1%) 98 (79%) 59 (62.1%) 
Number of patients completing 6MWD 130 (90%) 92 (67.6%) 77 (64.7%) 76 (77.5%) 43 (72.9%) 
Number of patients with NYHA score 145 (100%) 127 (93.4%) 112 (94.1%) 90 (91.8%) 55 (93.2%) 
Number of patients completing descriptive EQ-5D assessment 137 (94.5%) 107 (78.7%) 95 (79.8%) 90 (91.8%) 55 (93.2%) 
Number of patients completing EQ-VAS 135 (93.1%) 101 (74.8%) 92 (77.3%) 80 (81.6%) 59 (100%) 
 Baseline 30 days 6 months 12 months 24 months 
Number of patients available for follow-up at the prespecified time interval 145 145 135 124 95 
Number of patients surviving 145 (100%) 136 (93.8%) 119 (88.1%) 98 (79%) 59 (62.1%) 
Number of patients completing 6MWD 130 (90%) 92 (67.6%) 77 (64.7%) 76 (77.5%) 43 (72.9%) 
Number of patients with NYHA score 145 (100%) 127 (93.4%) 112 (94.1%) 90 (91.8%) 55 (93.2%) 
Number of patients completing descriptive EQ-5D assessment 137 (94.5%) 107 (78.7%) 95 (79.8%) 90 (91.8%) 55 (93.2%) 
Number of patients completing EQ-VAS 135 (93.1%) 101 (74.8%) 92 (77.3%) 80 (81.6%) 59 (100%) 

6MWD, 6-minute walking distance; NYHA, New York Heart Association; EQ-5D, EuroQol-5D; EQ-VAS, visual analogue scale.

Evolution of New York Heart Association functional class

New York Heart Association functional class could be assessed at baseline in all patients, but was missing at 30-day and at 6-, 12-, and 24-month follow-up in those who died (n = 9, 16, 26, and 36, respectively), or missed their evaluation for various other reasons (in 9, 7, 8, and 4 patients, respectively) including stroke (n = 2), disabling locomotor conditions (n = 3), and unreported reasons in the other (Table 3). Distribution of NYHA class groups is presented in Figure 1. A significant improvement in NYHA class was seen in surviving patients from baseline to 30 days [from 19 patients (13%) to 109 patients (85.8%) in NYHA class I/II; P < 0.001]. Six, 12, and 24 months after TAVI, this significant improvement (P < 0.001) was confirmed with 98 (87.5%), 80 (88.8%), and 44 surviving patients (80%) still functioning in NYHA class I/II, respectively.

Figure 1

Evolution of New York Heart Association functional class after transcatheter aortic valve implantation.

Figure 1

Evolution of New York Heart Association functional class after transcatheter aortic valve implantation.

When limiting the analysis to the 59 survivors at 24 months, this significant improvement in NYHA class was confirmed (data not shown). However, non-survivors or patients lost to follow-up appeared to be in worse functional condition at baseline (36.6% NYHA class 4; 56.1% NYHA class 3) when compared with survivors (15.5% NYHA class 4; 74% NYHA class 3; P = 0.006). There was no difference in improvement of NYHA class between patients treated using a transfemoral access compared with a transapical approach (P = 0.9261), neither between patients younger or older than 80 years (P = 0.7856).

Evolution of the 6-minute walking distance

A baseline 6MWD was available in 130 patients (90%). In 15 patients, 6MWD was not performed because of severe obstructive pulmonary disease (n = 7), disabling locomotor conditions (n = 3), or unreported causes in the other patients. At 30 days as well as 6, 12, and 24 months, a 6MWD was available in 92 (67.6%), 77 (64.7%), 76 (77.6%), and 43 (72.9%) surviving patients, respectively (Table 3). Reasons for not performing the test at follow-up consultations include ischaemic stroke (n = 7), disabling locomotor conditions (n = 9), frailty (n = 7), procedure-related complications with delayed recovery and respiratory limitations (n = 4), follow-up in another centre (n= 6), and unspecified reasons in the remaining patients.

At baseline, absolute 6MWD was 238 m [164; 307], representing 46% [33; 60] of the expected distance based on age, gender, and stature (Figures 2 and 3). Distance covered by surviving patients increased significantly at 30-day follow-up with 19.3 ± 8.2 m [95% CI 3.1; 35.5; (P = 0.0499)], or an improvement of 3.3 ± 1.6% of the expected distance [95% CI 0.2; 6.5; (P = 0.0751)]. From baseline to 6-month follow-up, the 6MWD increased with 23.3 ± 8.1 m [95% CI 7.3; 39.3; (P = 0.0194)] or with 4.3 ± 1.7% (95% CI 0.9; 7.6) of the expected distance (P = 0.0521). At 12-month follow-up, the 6MWD trended to increase with 17.1 ± 8.8 m [95% CI −0.4; 34.6; (P = 0.1879)] or 2.1 ± 1.9% (95% CI −1.8; 5.9) of the expected distance (P = 0.3571), while at 24 months after TAVI, 6MWD came back to values similar to those before TAVI [+7.2 ± 9.3 m; 95% CI −13.9; 28.4; (P = 0.6729)] or +0.6 ± 2.4% (95% CI −4.1; 5.3) of the expected distance (P = 0.7179).

Figure 2

Evolution of 6-minute walking distance after transcatheter aortic valve implantation. Absolute 6-minute walking distance in metres at baseline and follow-up is presented as median [interquartile range]. Change from baseline is presented as mean and standard deviation and 95% confidence interval.

Figure 2

Evolution of 6-minute walking distance after transcatheter aortic valve implantation. Absolute 6-minute walking distance in metres at baseline and follow-up is presented as median [interquartile range]. Change from baseline is presented as mean and standard deviation and 95% confidence interval.

Figure 3

Evolution of effective vs. expected 6-minute walking distance after transcatheter aortic valve implantation. Proportional 6-minute walking distance (percent of expected distance) at baseline and follow-up is presented as median [interquartile range]. Change from baseline is presented as mean and standard deviation and 95% confidence interval.

Figure 3

Evolution of effective vs. expected 6-minute walking distance after transcatheter aortic valve implantation. Proportional 6-minute walking distance (percent of expected distance) at baseline and follow-up is presented as median [interquartile range]. Change from baseline is presented as mean and standard deviation and 95% confidence interval.

There were no significant differences in baseline 6MWD between the 59 long-term survivors and those dying within 2 years or lost to follow-up. The significant improvement at 30-day and 6-month follow-up was confirmed in the surviving group (data not shown). There was no significant difference in change of 6MWD between patients treated using a transfemoral access compared with the transapical approach (P = 0.6719), neither between patients younger or older than 80 years (P = 0.0702). Patients in baseline NYHA class I/II progressed significantly more at 30 days (P= 0.0007 and 0.0256) as well as 6 (P = 0.0004 and 0.0081) and 12 months (P = 0.0073 and 0.0469) when compared with those in baseline NYHA class III/IV, both in absolute 6MWD and in the percentage of predicted distance. This trend remained at 24 months, but was no longer significant (P = 0.0894 and 0.1228).

Evolution of quality-of-life score

The EQ-5D descriptive assessment was completed at baseline in 137 patients (94.5%), and in 107 (78.7%), 95 (79.8%), 90 (91.8%), and 55 (93.2%) surviving patients at 30-day as well as 6-, 12-, and 24-month follow-up, respectively (Table 3 and Figure 4). Reasons for not performing the test include stroke (n = 5), cognitive impairment (n = 8), follow-up in another centre (n = 6), and unspecified reasons in the remaining patients. EuroQol-5D score at baseline (0.602 [0.366; 0.805]) progressed with 0.044 ± 0.0283 at 30 days [95% CI −0.0122; 0.0997; (P = 0.4323)], with 0.053 ± 0.0285 at 6 months [95% CI −0.0033; 0.1096; (P = 0.3842)] and with 0.032 ± 0.296 at 12 months [95% CI −0.0268; 0.0907; (P = 0.8411)]. At 24 months, the EQ-5D score became similar to baseline values [−0.018 ± 0.0354; 95% CI −0.0889; 0.0531; (P = 0.8411)].

Figure 4

EuroQol-5D and visual analogue scale quality-of-life scores before and after transcatheter aortic valve implantation. EuroQol-5D and visual analogue scale indices at baseline and follow-up are presented as median [interquartile range] values.

Figure 4

EuroQol-5D and visual analogue scale quality-of-life scores before and after transcatheter aortic valve implantation. EuroQol-5D and visual analogue scale indices at baseline and follow-up are presented as median [interquartile range] values.

In contrast, the EQ-VAS, recording an individual's rating for his current health-related QoL state, showed a significant and sustained improvement in QoL from 65% [50; 75] at baseline to 75% [65; 80] at 30 days (P = 0.0166), 70% [60; 80] at 6 months (P = 0.0014), 70% [60; 80] at 12 months (P = 0.0180), and 70% [60; 80] (P = 0.0166) at 24 months.

There were no significant differences in EQ-5D score at baseline between the 59 survivors at 2-year follow-up and those patients who had died or were lost to follow-up. Limiting our QoL analysis to long-term survivors only, no significant improvement in the EQ-5D descriptive assessment was observed, while again a sustained improvement was confirmed in EQ-VAS scoring (data not shown).

There was no difference in evolution of EQ-5D score after a transfemoral approach compared with the transapical approach (P = 0.1814), nor between age groups (<80 compared with ≥80 years). The EQ-5D score improved significantly more in patients with a baseline functional NYHA class I/II compared with class III/IV, showing a significant difference at 24-month follow-up (P < 0.001).

No significant changes were observed at any time in the individual health domains of the EQ-5D assessment, except for an improvement in degree of self-care at 24 months after TAVI (P = 0.0116).

Discussion

Besides prolonging life, SAVR in octogenarians results in an improvement in QoL of similar magnitude as in younger patients.16 In elderly patients with symptomatic severe aortic valve stenosis at prohibitive risk for SAVR, relief of symptoms and improvement in QoL with TAVI might even be of greater importance than the sole gain in life expectancy, since it allows to maintain (or regain) as much personal independence as possible.17 In the present study, TAVI in an aged patient population with multiple comorbidities pointed towards an improvement of functional performance at 30-day and 6-month follow-up, when evaluated with an objective measure of 6MWD, but not with EQ-5D descriptive QoL scoring. Importantly, more subjective measures of functional performance (NYHA functional class) and general well-being (EQ-VAS QoL scoring) showed a significant and sustained benefit of TAVI up to 24 months of follow-up. The lack of multiparametric and sustained improvement in all measurable parameters of physical functioning has been used as an argument to question the cost–benefit ratio of TAVI, and even to withhold reimbursement of this disruptive technology based on an argument of futility.18 Therefore, a different approach to the assessment of functional performance and QoL, tailored to the specific patient population undergoing TAVI, seems appropriate to unravel these softer endpoints of subjective well-being. Such tailored approach may go beyond the traditional dichotomic subgroup assessments based on age, gender, and access route, which, according to our analyses, did not show differences in progress of NYHA, 6MWD, and QoL.

Similar to the present study, most series report significant improvements in NYHA functional class up to 3–5 years after TAVI.19,20 However, NYHA functional class often poorly correlates with an objectively measured exercise capacity, remains highly subjective, and is prone to overestimating improvement in treated subjects, even in the few randomized, but non-blinded trials. Moreover, Gotzmann et al.21 reported a heterogeneous within-group variability, demonstrating that up to 21% of patients do not improve after TAVI or even have a decline in NYHA class. As recently stated by Kim et al.,20 NYHA classification should therefore not be used as a stand-alone tool to evaluate functional performance, especially in a heterogeneous patient population.

The absolute change in 6MWD and the change in ratio of effective vs. predicted distance based on age, gender, and stature have been proposed as valuable alternatives to assess functional performance in patients with heart failure and after cardiac surgery, and could therefore also be used to assess the impact of TAVI. In surgical patients, an increase of ∼10% in 6MWD between the initial and final test has been suggested as an indication of a clinically relevant improvement in functional capacity as a consequence of the intervention.22 This 10% rule seems to be in line with the improvement in 6MWD at 30 days and 6 months in our series. However, the degree of improvement in walking distance and the lack of sustained benefit after 6 months in our study seem to be influenced by a multitude of comorbidities in a very aged patient population, severely compromising the interpretation of a crude walking distance. Indeed, compared with previous studies, our population had a slightly longer walking distance at baseline, and confirming previous reports, they also gained fewer absolute metres at 6-month follow-up.23–27 Despite the haemodynamic improvement, many patients in our series had moderate anaemia following TAVI (52% of patients requiring transfusion of a median of 2 units of red blood cells), and were limited by a variable pulmonary or locomotor state. Moreover, a relatively large proportion of patients missed their 6MWD test on later follow-up consultations (Table 3) and a multiple imputation analysis to compensate for these missing data failed to show further improvement over time.

Russo et al. have recently demonstrated the usefulness of cardiac rehabilitation after TAVI, even in octogenerians, were a significant improvement in 6MWD was observed after a mean training period of 2 weeks. Improvement in patients able to walk was similar in the TAVI group compared with a matched patient population undergoing SAVR.28 This emphasizes the potential to further maximize the haemodynamic benefit of valve replacement in optimizing functional performance after TAVI and allowing this patient population to regain as much personal independence as possible.

The impact of novel technologies on QoL remains difficult to quantify, especially in patients with comorbidities interfering with their general well-being. We used the EQ-5D health-related measure, which is relatively easy to perform at different points in time, and has been reported in several other studies evaluating QoL after TAVI. Similar to the outcomes reported by Fairbairn et al.,29 the largest benefit in QoL in our population was detected at 30 days post-TAVI, although this improvement did not reach statistical significance. This absolute improvement in EQ-5D score was sustained at 6 months, but became less apparent at 12 and certainly at 24 months. Of note, most studies used the English version of the EQ-5D, with a broader range between the best (=1) and worst (= −0.59) index, making direct comparisons between our and other studies difficult. When using the English version, a gain/loss of 0.074 has been proposed as a cut-off value to detect a clinically relevant change in EQ-5D score. In the absence of a validated cut-off for improvement when using the Dutch version of the EQ-5D, and despite not reaching statistical significance, we cannot exclude that a progress of 0.044 and 0.053 points at 1- and 6-month follow-up has no clinical relevance at all, especially taking into account the more narrow range of the Dutch score. While some studies report a continued benefit in QoL at 1 year after TAVI and good clinical results at 5-year follow-up in surviving patients, others, as in ours, report a more marginal, non-significant benefit during prolonged follow-up, often related to a higher absolute score at baseline.30 When analysing individual components of the EQ-5D score, we could not demonstrate a significant improvement in either domain, apart from a significant improvement in degree of self-care at 24 months after TAVI, which may have been a chance finding. The questionnaire, however, showed that 15% of patients could walk easily, 41% had no problems with self-care, 17% had no difficulties in performing daily activities, 69% was free of pain, and 69% were neither anxious nor depressed. These results were remarkably worse than those previously reported by Bouleti et al.,19 even at 5 years of follow-up, where 33% of patients could walk easily, 76% had no problem with self-care, 50% had no difficulties in performing their daily activities, 50% were free of pain, and 50% were neither anxious nor depressed. Interestingly, individual's rating for their current health-related QoL state in our series (EQ-VAS) contradicted the EQ-5D descriptive scoring, with a sustained improvement in QoL up to 24 months of follow-up in our analysis, similar to the results reported by Bouleti et al. This discrepancy could either be attributed to a psychological effect of the TAVI procedure or to the limited specificity of the EQ-5D descriptive assessment to detect meaningful improvement in QoL in comorbid TAVI patients. Importantly, we did not compare the evolution of the EQ-5D score in TAVI patients to a medically managed control group. Indeed, in a high-risk geriatric patient population, preventing further decline might be interpreted as a substantial achievement in terms of QoL compared with the unfavourable natural evolution of symptomatic aortic valve stenosis. In this respect, adding life to years may be especially valuable rather than solely adding years to life.

In line with other studies, patients in our study with a more favourable baseline functional NYHA class I/II showed most benefit in terms of QoL when compared with patients in NYHA class III/IV.29 This finding may be counterintuitive, since the potential for improvement of dyspnoea and derived NYHA class after TAVI is expected to be the highest in patients with NYHA III/IV. However, baseline NYHA class III/IV is often a marker of comorbidity, and may therefore identify patients with a lot of confounding and non-modifiable factors impacting on exercise capacity. We used the Charlson comorbidity index trying to quantify the impact of associated diseases on outcomes. While this score only partially accounts for the general disease state of our population, values in our series were somewhat lower than those reported by Bouleti et al., and scores at baseline did not appear to be different between long-term survivors and the rest of our population.

For the same reason of comorbidities primarily driving the potential for improvement of QoL, we did not confirm a more pronounced benefit in QoL after TAVI in patients <80 years when compared with ≥80 years, nor in males vs. females as previously reported.29

The EQ-5D assessment may, however, not be the most reliable tool to assess QoL after TAVI. Several studies using this general health-related measure reported inconsistent results, while other general health-related measures such as the Medical Outcomes Study Short Form-12 and-36 questionnaires, or disease-specific measures such as the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Minnesota Living With Heart Failure Questionnaire were consistently associated with an improved QoL after TAVI, despite not having been designed for or validated in this specific patient population.20,25,29–31 A worse health status, as assessed with the KCCQ, has also been associated with higher long-term mortality after TAVI.32 Finally, one study reporting both KCCQ and EQ-5D showed a marked improvement in QoL using the KCCQ at 1 year while only a modest improvement was shown using EQ-5D, stressing the need for a comprehensive approach of the assessment of QoL, including a frailty index for individual patients. Indeed, frailty has been identified as one of the most powerful predictors of death, myocardial infarction, stroke, or heart failure after TAVI.33 Frailty seems not to be linked to procedural outcome, but the use of a frailty score based on gait speed, grip strength, activities of daily life, and serum albumin has been associated with an increased 1-year mortality and a higher rate of poor outcome after TAVI.34 Therefore, combined frailty indices based on a more detailed assessment of cognition, mobility, nutrition, instrumental, and basic activities of daily life may be better suited to independently predict functional decline after TAVI.35,36 Since frailty might be endemic in the patient population referred for TAVI, Afilalo et al. raised the important question whether the role of frailty assessment may ultimately prove to be in identifying who is not frail and may benefit from SAVR or at the other end identify the extremely frail patients who would better be managed medically without intervention.37

Our study has several limitations. First, the findings of our study are based on data of a single centre and should therefore be interpreted with caution. Secondly, although our population is one of the larger patient populations reporting on the issue, the patient sample size is rather small. Thirdly, interpretation of the 6MWD and EQ-5D was incomplete, despite standardized follow-up with dedicated nurses. To account for mortality throughout the study, a longitudinal GEE model was used and data missing for reasons other than death were imputed using multiple imputation techniques. This did not change results in EQ-5D assessment or 6MWD at the different points in time. Finally, since we used the Dutch version of the EQ-5D assessment, having a more narrow range from 1 to −0.33, direct comparisons of absolute QoL scores and reported changes between our study and others will be difficult.

We conclude that in high-risk comorbid patients with symptomatic aortic valve stenosis, TAVI resulted in a significant improvement of functional capacity at 30-day and 6-month follow-up, when evaluated by objective measures as a 6MWD and up to 24 months when using the NYHA functional class. This gain in functional performance resulted in an improvement in QoL as assessed with the EQ-VAS, a finding that could not be confirmed using the Dutch version of the EQ-5D descriptive health assessment, most likely related to multiple comorbidities driving the outcome of this assessment. A multimodality evaluation of functional performance and QoL, tailored to the specific patient population undergoing TAVI, seems therefore the preferred approach to couple crude survival benefit with subjective well-being after TAVI.

Funding

C.D. is holder of a Medical Education grant from Boston Scientific (Donald Baim Chair of Interventional Cardiology).

Conflict of interest: C.D. is a TAVI proctor for Edwards Lifesciences.

References

1
Iung
B
,
Baron
G
,
Butchart
EG
,
Delahaye
F
,
Gohlke-Bärwolf
C
,
Levang
OW
,
Tornos
P
,
Vanoverschelde
J-L
,
Vermeer
F
,
Boersma
E
,
Ravaud
P
,
Vahanian
A
.
A prospective survey of patients with valvular heart disease in Europe: the Euro Heart Survey on Valvular Heart Disease
.
Eur Heart J
 
2003
;
24
:
1231
1243
.
2
Carabello
BA
,
Paulus
WJ
.
Aortic stenosis
.
Lancet
 
2009
;
373
:
956
966
.
3
Iung
B
,
Cachier
A
,
Baron
G
,
Messika-Zeitoun
D
,
Delahaye
F
,
Tornos
P
,
Gohlke-Barwolf
C
,
Boersma
E
,
Ravaud
P
,
Vahanian
A
.
Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery?
Eur Heart J
 
2005
;
26
:
2714
2720
.
4
Joint Task Force on the Management of Valvular Heart Disease of the European Society of C, European Association for Cardio-Thoracic S
,
Vahanian
A
,
Alfieri
O
,
Andreotti
F
,
Antunes
MJ
,
Baron-Esquivias
G
,
Baumgartner
H
,
Borger
MA
,
Carrel
TP
,
De Bonis
M
,
Evangelista
A
,
Falk
V
,
Iung
B
,
Lancellotti
P
,
Pierard
L
,
Price
S
,
Schafers
HJ
,
Schuler
G
,
Stepinska
J
,
Swedberg
K
,
Takkenberg
J
,
Von Oppell
UO
,
Windecker
S
,
Zamorano
JL
,
Zembala
M
.
Guidelines on the management of valvular heart disease (version 2012)
.
Eur Heart J
 
2012
;
33
:
2451
2496
.
5
Nishimura
RA
,
Otto
CM
,
Bonow
RO
,
Carabello
BA
,
Erwin
JP
3rd
,
Guyton
RA
,
O'Gara
PT
,
Ruiz
CE
,
Skubas
NJ
,
Sorajja
P
,
Sundt
TM
3rd
,
Thomas
JD
,
American College of Cardiology/American Heart Association Task Force on Practice G
.
2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
.
J Am Coll Cardiol
 
2014
;
63
:
e57
e185
.
6
Charlson
ME
,
Pompei
P
,
Ales
KL
,
MacKenzie
CR
.
A new method of classifying prognostic comorbidity in longitudinal studies: development and validation
.
J Chronic Dis
 
1987
;
40
:
373
383
.
7
Michel
P
,
Roques
F
,
Nashef
SA
,
Euro
SPG
.
Logistic or additive EuroSCORE for high-risk patients?
Eur J Cardiothorac Surg
 
2003
;
23
:
684
687
;
discussion 7
.
8
Nashef
SA
,
Roques
F
,
Sharples
LD
,
Nilsson
J
,
Smith
C
,
Goldstone
AR
,
Lockowandt
U
.
EuroSCORE II
.
Eur J Cardiothorac Surg
 
2012
;
41
:
734
744
;
discussion 44–5
.
9
O'Brien
SM
,
Shahian
DM
,
Filardo
G
,
Ferraris
VA
,
Haan
CK
,
Rich
JB
,
Normand
SL
,
DeLong
ER
,
Shewan
CM
,
Dokholyan
RS
,
Peterson
ED
,
Edwards
FH
,
Anderson
RP
,
Society of Thoracic Surgeons Quality Measurement Task F
.
The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2—isolated valve surgery
.
Ann Thorac Surg
 
2009
;
88
(1 Suppl)
:
S23
S42
.
10
Galie
N
,
Humbert
M
,
Vachiery
JL
,
Gibbs
S
,
Lang
I
,
Torbicki
A
,
Simonneau
G
,
Peacock
A
,
Vonk Noordegraaf
A
,
Beghetti
M
,
Ghofrani
A
,
Gomez Sanchez
MA
,
Hansmann
G
,
Klepetko
W
,
Lancellotti
P
,
Matucci
M
,
McDonagh
T
,
Pierard
LA
,
Trindade
PT
,
Zompatori
M
,
Hoeper
M
,
Aboyans
V
,
Vaz Carneiro
A
,
Achenbach
S
,
Agewall
S
,
Allanore
Y
,
Asteggiano
R
,
Paolo Badano
L
,
Albert Barbera
J
,
Bouvaist
H
,
Bueno
H
,
Byrne
RA
,
Carerj
S
,
Castro
G
,
Erol
C
,
Falk
V
,
Funck-Brentano
C
,
Gorenflo
M
,
Granton
J
,
Iung
B
,
Kiely
DG
,
Kirchhof
P
,
Kjellstrom
B
,
Landmesser
U
,
Lekakis
J
,
Lionis
C
,
Lip
GY
,
Orfanos
SE
,
Park
MH
,
Piepoli
MF
,
Ponikowski
P
,
Revel
MP
,
Rigau
D
,
Rosenkranz
S
,
Voller
H
,
Luis Zamorano
J
.
2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)
.
Eur Heart J
 
2016
;
37
:
67
119
.
11
Enright
PL
,
Sherrill
DL
.
Reference equations for the six-minute walk in healthy adults
.
Am J Respir Crit Care Med
 
1998
;
158
:
1384
1387
.
12
Dyer
MT
,
Goldsmith
KA
,
Sharples
LS
,
Buxton
MJ
.
A review of health utilities using the EQ-5D in studies of cardiovascular disease
.
Health Qual Life Outcomes
 
2010
;
8
:
13
.
13
Lamers
LM
,
Stalmeier
PF
,
McDonnell
J
,
Krabbe
PF
,
van Busschbach
JJ
.
Measuring the quality of life in economic evaluations: the Dutch EQ-5D tariff
.
Ned Tijdschr Geneeskd
 
2005
;
149
:
1574
1578
.
14
Liang
K-Y
,
Zeger
SL
.
Longitudinal data analysis using generalized linear models
.
Biometrika
 
1986
;
73
:
13
22
.
15
Rubin
D
.
Multiple imputation for nonresponse in surveys
 .
New York, USA
:
John Willey & Sons
,
1987
.
16
Olsson
M
,
Janfjäll
H
,
Orth-Gomér
K
,
Undén
A
,
Rosenqvist
M
.
Quality of life in octogenarians after valve replacement due to aortic stenosis: a prospective comparison with younger patients
.
Eur Heart J
 
1996
;
17
:
583
589
.
17
Smith
CR
,
Leon
MB
,
Mack
MJ
,
Miller
DC
,
Moses
JW
,
Svensson
LG
,
Tuzcu
EM
,
Webb
JG
,
Fontana
GP
,
Makkar
RR
,
Williams
M
,
Dewey
T
,
Kapadia
S
,
Babaliaros
V
,
Thourani
VH
,
Corso
P
,
Pichard
AD
,
Bavaria
JE
,
Herrmann
HC
,
Akin
JJ
,
Anderson
WN
,
Wang
D
,
Pocock
SJ
,
PARTNER Trial Investigators
.
Transcatheter versus surgical aortic-valve replacement in high-risk patients
.
N Engl J Med
 
2011
;
364
:
2187
2198
.
18
Neyt
M
,
Van Brabandt
H
,
Devriese
S
,
Van De Sande
S
.
A cost-utility analysis of transcatheter aortic valve implantation in Belgium: focusing on a well-defined and identifiable population
.
BMJ open
 
2012
;
2
:
1
8
.
19
Bouleti
C
,
Himbert
D
,
Iung
B
,
Alos
B
,
Kerneis
C
,
Ghodbane
W
,
Messika-Zeitoun
D
,
Brochet
E
,
Fassa
AA
,
Depoix
JP
,
Ou
P
,
Nataf
P
,
Vahanian
A
.
Long-term outcome after transcatheter aortic valve implantation
.
Heart
 
2015
;
101
:
936
942
.
20
Kim
CA
,
Rasania
SP
,
Afilalo
J
,
Popma
JJ
,
Lipsitz
LA
,
Kim
DH
.
Functional status and quality of life after transcatheter aortic valve replacement: a systematic review
.
Ann Int Med
 
2014
;
160
:
243
254
.
21
Gotzmann
M
,
Pljakic
A
,
Bojara
W
,
Lindstaedt
M
,
Ewers
A
,
Germing
A
,
Mugge
A
.
Transcatheter aortic valve implantation in patients with severe symptomatic aortic valve stenosis—predictors of mortality and poor treatment response
.
Am Heart J
 
2011
;
162
:
238
245
.
e1
.
22
Fiorina
C
,
Vizzardi
E
,
Lorusso
R
,
Maggio
M
,
De Cicco
G
,
Nodari
S
,
Faggiano
P
,
Dei Cas
L
.
The 6-min walking test early after cardiac surgery. Reference values and the effects of rehabilitation programme
.
Eur J Cardiothorac Surg
 
2007
;
32
:
724
729
.
23
Bagur
R
,
Rodes-Cabau
J
,
Dumont
E
,
Larochelliere
RD
,
Doyle
D
,
Bertrand
OF
,
Cote
M
,
Poirier
P
,
Pibarot
P
.
Exercise capacity in patients with severe symptomatic aortic stenosis before and six months after transcatheter aortic valve implantation
.
Am J Cardiol
 
2011
;
108
:
258
264
.
24
Gotzmann
M
,
Lindstaedt
M
,
Bojara
W
,
Ewers
A
,
Mugge
A
.
Clinical outcome of transcatheter aortic valve implantation in patients with low-flow, low gradient aortic stenosis
.
Catheter Cardiovasc Interv
 
2012
;
79
:
693
701
.
25
Gotzmann
M
,
Hehen
T
,
Germing
A
,
Lindstaedt
M
,
Yazar
A
,
Laczkovics
A
,
Mumme
A
,
Mugge
A
,
Bojara
W
.
Short-term effects of transcatheter aortic valve implantation on neurohormonal activation, quality of life and 6-minute walk test in severe and symptomatic aortic stenosis
.
Heart
 
2010
;
96
:
1102
1106
.
26
Bagur
R
,
Rodes-Cabau
J
,
Dumont
E
,
De Larochelliere
R
,
Doyle
D
,
Pibarot
P
,
Cote
M
,
Clavel
MA
,
Villeneuve
J
,
Gutierrez
M
,
Poirier
P
,
Bertrand
OF
.
Performance-based functional assessment of patients undergoing transcatheter aortic valve implantation
.
Am Heart J
 
2011
;
161
:
726
734
.
27
Green
P
,
Kirtane
A
,
Genereux
P
,
McAndrew
T
,
Hueter
I
,
Alu
M
,
Arnold
S
,
Beohar
N
,
Rihal
C
,
Mack
M
,
Kapadia
S
,
Maurer
M
,
Williams
M
,
Kodali
S
,
Leon
M
,
Cohen
D
.
The impact of six–minute walk test performance on outcomes after transcatheter aortic valve replacement: insights from the partner trial
.
J Am Coll Cardiol
 
2013
;
61
(10 Suppl)
:
E1971
.
28
Russo
N
,
Compostella
L
,
Tarantini
G
,
Setzu
T
,
Napodano
M
,
Bottio
T
,
D'Onofrio
A
,
Isabella
G
,
Gerosa
G
,
Iliceto
S
,
Bellotto
F
.
Cardiac rehabilitation after transcatheter versus surgical prosthetic valve implantation for aortic stenosis in the elderly
.
Eur J Prevent Cardiol
 
2014
;
21
:
1341
1348
.
29
Fairbairn
TA
,
Meads
DM
,
Mather
AN
,
Motwani
M
,
Pavitt
S
,
Plein
S
,
Blackman
DJ
,
Greenwood
JP
.
Serial change in health-related quality of life over 1 year after transcatheter aortic valve implantation: predictors of health outcomes
.
J Am Coll Cardiol
 
2012
;
59
:
1672
1680
.
30
Lefevre
T
,
Kappetein
AP
,
Wolner
E
,
Nataf
P
,
Thomas
M
,
Schachinger
V
,
De Bruyne
B
,
Eltchaninoff
H
,
Thielmann
M
,
Himbert
D
,
Romano
M
,
Serruys
P
,
Wimmer-Greinecker
G
,
Group
PEI
.
One year follow-up of the multi-centre European PARTNER transcatheter heart valve study
.
Eur Heart J
 
2011
;
32
:
148
157
.
31
Reynolds
MR
,
Magnuson
EA
,
Wang
K
,
Thourani
VH
,
Williams
M
,
Zajarias
A
,
Rihal
CS
,
Brown
DL
,
Smith
CR
,
Leon
MB
,
Cohen
DJ
.
Health-related quality of life after transcatheter or surgical aortic valve replacement in high-risk patients with severe aortic stenosis: results from the PARTNER (Placement of AoRTic TraNscathetER Valve) Trial (Cohort A)
.
J Am Coll Cardiol
 
2012
;
60
:
548
558
.
32
Arnold
S
,
Spertus
J
,
Vemulapalli
S
,
Dai
D
,
O'Brien
S
,
Baron
S
,
Kirtane
A
,
Mack
M
,
Green
P
,
Reynolds
M
,
Rumsfeld
J
,
Cohen
D
.
Association of disease-specific health status with long-term mortality after transcatheter aortic valve replacement
.
J Am Coll Cardiol
 
2015
;
65
(10 Suppl)
:
A1949
.
33
Ewe
SH
,
Ajmone Marsan
N
,
Pepi
M
,
Delgado
V
,
Tamborini
G
,
Muratori
M
,
Ng
AC
,
van der Kley
F
,
de Weger
A
,
Schalij
MJ
,
Fusari
M
,
Biglioli
P
,
Bax
JJ
.
Impact of left ventricular systolic function on clinical and echocardiographic outcomes following transcatheter aortic valve implantation for severe aortic stenosis
.
Am Heart J
 
2010
;
160
:
1113
1120
.
34
Green
P
,
Arnold
S
,
Cohen
D
,
Kirtane
A
,
Kodali
S
,
Brown
D
,
Rihal
C
,
Lei
Y
,
Kim
R
,
Alu
M
,
Leon
M
,
Mack
M
.
Poor outcome after transcatheter aortic valve replacement: associations of mortality and quality of life with frailty in the PARTNER trial
.
J Am Coll Cardiol
 
2015
;
65
(10 Suppl)
:
A1967
.
35
Schoenenberger
AW
,
Stortecky
S
,
Neumann
S
,
Moser
A
,
Jüni
P
,
Carrel
T
,
Huber
C
,
Gandon
M
,
Bischoff
S
,
Schoenenberger
C-M
,
Stuck
AE
,
Windecker
S
,
Wenaweser
P
.
Predictors of functional decline in elderly patients undergoing transcatheter aortic valve implantation (TAVI)
.
Eur Heart J
 
2013
;
34
:
684
692
.
36
Green
P
,
Woglom
AE
,
Genereux
P
,
Daneault
B
,
Paradis
JM
,
Schnell
S
,
Hawkey
M
,
Maurer
MS
,
Kirtane
AJ
,
Kodali
S
,
Moses
JW
,
Leon
MB
,
Smith
CR
,
Williams
M
.
The impact of frailty status on survival after transcatheter aortic valve replacement in older adults with severe aortic stenosis: a single-center experience
.
JACC Cardiovasc Interv
 
2012
;
5
:
974
981
.
37
Afilalo
J
,
Alexander
KP
,
Mack
MJ
,
Maurer
MS
,
Green
P
,
Allen
LA
,
Popma
JJ
,
Ferrucci
L
,
Forman
DE
.
Frailty assessment in the cardiovascular care of older adults
.
J Am Coll Cardiol
 
2014
;
63
:
747
762
.