Long-Term Mortality and Quality of Life After Transcatheter Aortic Valve Insertion in Very Elderly Patients

Abstract: Background. We sought to compare long-term mortality and quality of life (QoL) in very elderly (≥80 years) patients undergoing transcatheter aortic valve implantation (TAVI) in comparison with younger patients (<80 years). Methods. A total of 101 patients treated with TAVI were divided into two groups according to age: <80 years (n = 42; 41.6%) and ≥80 years (n = 59; 58.4%). The baseline characteristics, including procedural outcomes as well as frailty and QoL assessment were compared between age groups. Results. Very elderly patients (≥80 years) were more frequently female, with a higher estimated risk of death based on STS score. Other baseline characteristics, including frailty indices, were comparable between groups. No difference in complication rate between age groups was observed. At 12 months, mortality rates were comparable for patients <80 years vs ≥80 years (16.7% vs 18.6%, respectively; P=.99). An improvement in QoL after 12 months as assessed by EQ-5D-3L was confirmed for both age groups, but with more pronounced beneficial effect of TAVI in younger patients. Conclusion. The results of our single-center study showed that older age does not seem to be associated with impaired clinical outcomes after TAVI. However, benefit of TAVI in terms of long-term QoL improvement may be less apparent in very elderly patients.

J INVASIVE CARDIOL 2016;28(12):492-496. Epub 2016 October 15.

Key words: transcatheter aortic valve implantation, TAVI, TAVR, aortic valve disease

Transcatheter aortic valve implantation (TAVI) is a less invasive treatment option for elderly, high-risk patients with symptomatic severe aortic stenosis (AS) than surgical aortic valve replacement (AVR). TAVI improves survival and quality of life (QoL) as compared with medical treatment in inoperable patients.^1,2 TAVI is also non-inferior to AVR regarding survival in selected high-risk patients.³ The aim of all centers performing TAVI is to maintain the all-cause mortality rate at 30 days below the estimated risk by logistic EuroScore I and STS score.⁴ A successful TAVI procedure requires a complex selection of patients, including detailed imaging information of the aortic valve anatomy and the peripheral arteries, and also critical clinical assessment by an interdisciplinary heart team.⁵ The decision to perform TAVI in very elderly patients is challenging due to specific issues associated with a very advanced age (eg, frailty, co-morbidities, and cognitive impairment). These may be associated with impaired outcomes. In our study, we sought to compare long-term mortality and QoL in very elderly patients (≥80 years) undergoing TAVI in comparison with younger patients (<80 years). 

Methods

A total of 101 consecutive patients who underwent TAVI at our center were included. All patients were diagnosed with symptomatic severe AS and had high surgical risk or contraindications for AVR. Patients were clinically evaluated to assess operative risk, comorbidities, frailty, and procedural feasibility. Frailty index was assessed before TAVI with the Katz index of Independence of Activities in Daily Living (KI), Karnofsky Performance Status Scale (KPSS), elderly mobility scale score (EMS), Canadian Study of Health and Aging (CSHA) scale, 5-meter walking test (5MWT), dominant hand grip strength, body mass index (BMI), albumin infusion, and Identification of Seniors at Risk (ISAR) scale.^6-13 Hand grip strength was distinguished as follows: 1 = weak; 2 = mild; and 3 = strong. Albumin infusion was performed when serum albumin level was <3.5 g/L before index procedure. Patient screening and selection were performed by a multidisciplinary heart team supported by clinical and imaging resources. TAVI procedures were performed using Edwards Sapien, Edwards Sapien XT, Edwards Sapien 3 (Edwards Lifesciences), Medtronic CoreValve (Medtronic, Inc), and JenaValve (JenaValve Technology). Access routes were transfemoral and transapical. Procedures were performed under general anesthesia or analgosedation. Endpoints of the study included all-cause mortality at 12 months, as well as cerebrovascular events, myocardial infarction, bleeding complications, and the need for permanent pacemaker implantation. QoL was assessed with the validated Polish version of the EQ-5D-3L questionnaire at baseline and at 12 months after TAVI.² The visual analog scale (VAS) score, which is a part of the EQ-5D-3L, was also assessed. All endpoints were assessed according to the recommendations of the Valve Academic Research Consortium (VARC-2).¹⁴ The study was approved by the institutional ethical board and patients gave written informed consent for participation in the study.

Statistical analysis. Results are presented as number of patients (percentages) or median (interquartile range [IQR]) where applicable. Differences between groups were tested using Chi-square test and the Fisher’s exact test for dichotomous variables and the Mann-Whitney U-test for continuous variables. Changes in the proportions of patients who reported either “no problems” or “some problems”/“extreme problems” on the EQ-5D-3L between baseline and follow-up visits were analyzed using McNemar’s test. Differences in the VAS score and 6-minute walk test distance between baseline and follow-up assessments were analyzed with a Wilcoxon signed-rank test. All paired comparisons between baseline and 12-month measurements were performed excluding unpaired results. In addition, the difference in mortality between patients <80 and ≥80 years of age during follow-up was assessed by the Kaplan-Meier method. All tests were two-tailed, and a P-value <.05 was considered statistically significant. All statistical analyses were performed using SPSS 15.0 (SPSS, Inc).

Results

Of the 101 patients treated with TAVI, 42 patients (41.6%) were <80 years of age and the remaining 59 patients (58.4%) were very elderly, with age ≥80 years. Baseline clinical and echocardiographic characteristics for age groups are shown in Table 1. Very elderly patients were more frequently female, with a higher estimated risk of death based on STS score. The remaining clinical characteristics were comparable between groups. Somewhat unexpectedly, no differences in frailty indices between groups were observed (Table 2). Also, no difference in procedural technique was noted (Table 3). Bleeding complication rates (26.2% vs 33.9%; P=.51) and blood transfusion rates (23.8% vs 30.5%; P=.51) were similar for patients <80 years vs ≥80 years. Before TAVI, 16 patients (38%) <80 years and 19 patients (32.2%) ≥80 years were treated with triple-antiplatelet therapy (TAPT; acetylsalicylic acid, clopidogrel, and oral anticoagulant); 18 patients (42.8%) <80 years and 25 patients (42.3%) ≥80 years were treated with dual-antiplatelet therapy (DAPT; acetylsalicylic acid and clopidogrel); 4 patients (9.5%) <80 years and 8 patients (13.5%) ≥80 years were treated with acetylsalicylic acid only; and 4 patients (9.5%) <80 years and 7 patients (11.8%) ≥80 years were treated with a combination of acetylsalicylic acid and oral anticoagulant. All patients received acetylsalicylic acid together with clopidogrel after the procedure. Anticoagulation therapy in all patients with TAPT was bridged with low-molecular-weight heparin. All patients received a weight-adjusted dose of unfractionated heparin (UFH) during the procedure. There was no difference in bleeding event rates and blood transfusions between patients receiving DAPT vs TAPT at discharge.¹⁵ New-onset atrial fibrillation was diagnosed with the same frequency (7.1% vs 8.5%; P=.99) in both groups. The rate of grade 3 acute kidney injury was comparable between groups (2.4% vs 6.8%; P=.40). The length of hospital stay was similar in patients <80 years vs ≥80 years (10.5 days [IQR, 6.5-14.0 days] vs 9.5 days [7.0-14.0 days]; P=.99). There was no difference in the 12-month all-cause mortality rate between age groups (16.7% vs 18.6%; P=.99) (Figure 1). Similarly, no differences in the rates of cerebrovascular incident (9.5% vs 6.8%; P=.72) and myocardial infarction (4.8% vs 3.4%; P=.99) at 12 months were noted, according to VARC-2 criteria. New permanent pacemaker implantation was required in 14.3% of patients <80 years and 16.9% of patients ≥80 years (P=.79). 

Baseline QoL parameters assessed with EQ-5D-3L were comparable between age groups. An improvement in QoL after 12 months was confirmed for both age groups, but with more pronounced beneficial effect of TAVI in younger patients (Figure 2). Similarly, the median VAS score at baseline was comparable for patients <80 years vs ≥80 years (40.0 [IQR, 35.0-50.0] vs 40.0 [IQR, 35.0-50.0]; P=.60). However, there was a significant difference at 12 months in favor of younger patients (70.0 [IQR, 67.5-80.0] vs 70.0 [IQR, 60.0-70.0]; P=.03). 

Discussion

Our study showed that TAVI is associated with comparable long-term outcomes in patients <80 years and ≥80 years of age. Age is one of the variables included in currently used risk scores (logistic EuroScore I and II, as well as the STS score). The patients were treated with first-generation and second-generation devices, but that did not have an impact on mortality rate, corresponding with previously available data.¹⁶ Data from randomized controlled trials comparing TAVI vs surgical AVR or medical treatment demonstrated that age was not an independent determinant of 1-year all-cause mortality for patients treated with TAVI.^1,3,17 In the PARTNER B cohort, 46% of patients were >85 years old. Importantly, benefits from TAVI among very elderly patients were comparable with those observed in patients ≤85 years of age.¹ Another study has confirmed that both TAVI and surgical AVR in patients with AS >85 years old and high operative risk may provide similar outcomes.³ In addition, data from single-center or multicenter registries have confirmed that age does not significantly impact mid-term and long-term outcomes of patients undergoing TAVI.^18-24 The FRANCE-2 registry included 3195 patients treated by TAVI (mean age, 82.7 ± 7.2 years) and showed a 30-day mortality rate of 9.7%.²⁵ 

A substudy of the FRANCE-2 registry including 2254 patients >80 years showed that in patients within the age group of 80-84 years, the prevalence of diabetes, prior myocardial infarction, prior cardiac surgery, chronic obstructive pulmonary disease, and reduced left ventricular ejection fraction was significantly higher than in the patient groups 85-89 years and >90 years.^26,27 Surprisingly, transapical access, which is frequently used in patients with increased morbidity and mortality, was more common in the younger patients group (80-84 years) than in the other groups (85-89 years and >90 years; 20.5% vs 14.7% and 11.6%, respectively; P<.001). The presence of coronary artery disease, which may impact the survival rates in elderly patients after TAVI, was interestingly similar in both groups, as was myocardial infarction during follow-up.²⁸ The present study has additional value by showing similar long-term outcomes of patients treated by TAVI independent of age as well as comprehensive assessment of frailty and QoL among patients <80 years and ≥80 years. 

Appropriate and careful patient selection for TAVI in a multidisciplinary aspect may be associated with comparable outcomes in very elderly patients, in spite of the difference in age itself. Evaluation of frailty plays a crucial role in final patient assessment; however, it is frequently judged subjectively based on an “eyeball” test. It is generally agreed that frailty is a geriatric syndrome of impaired resiliency to stressors that results from deterioration in multiple physiological systems. As a result, the frail person is at increased risk of death from external stressors. However, there is no gold standard for defining and assessing frailty. Physical performance assessments such as gait speed and hand grip strength are more objective performance measures that may capture an individual’s overall functional status. Continuous measures, like 5MWT, are reproducible and can be repeated. Several publications deal with the impact of frailty on morbidity and mortality in elderly patients. It has been known for a long time that functional status (commonly evaluated by the ability to complete ADL and instrumental activities of daily living) is a strong predictor of morbidity and mortality in the geriatric population. Inouye et al found that any ADL impairment was associated with a 1.9-fold increased risk of all-cause mortality at 2 years in a population of patients ≥70 years admitted to general medicine departments.²⁹ Furthermore, it has been demonstrated that frailty and the onset of dependence in ADL are strongly associated.³⁰ Surprisingly, our results showed no significant differences in frailty assessment between younger and older patients. It is likely that frail patients among those ≥80 years were too sick to benefit from TAVI and were scheduled for optimal medical treatment or balloon aortic valvuloplasty.

QoL in the elderly is the result of multiple factors, including cardiac and non-cardiac comorbidities (eg, dementia or joint degeneration). The majority of these factors are not associated with the presence of AS; nonetheless, they can affect the QoL outcomes.³¹ In an elderly population with multiple comorbidities, the absolute survival benefit may be less substantial, increasing the importance of QoL. The improvement in QoL after TAVI may be higher than observed after AVR, even with the use of less invasive surgical techniques (mini thoracotomy, mini sternotomy).³² In our study the greatest improvement among patients ≥80 years in QoL was found in usual activities and pain/discomfort, but not in other aspects like mobility, self-care, and anxiety/depression, probably limited with factors not associated with AS. A plausible explanation for less apparent improvements in QoL in the very elderly could be higher STS risk score and a numerically higher number of transapical access sites in those patients.

Study limitations. The present investigation represents a single-center experience with a relatively small sample size, which could be regarded as a limitation of the study. However, these cases represent a complete analysis of consecutive patients without any exclusion criteria and with follow-up data available for all patients.

Conclusion

The results of our single-center study showed that older age does not seem to be associated with impaired clinical outcomes after TAVI. However, the benefit of TAVI in terms of long-term QoL improvement may be less apparent in very elderly patients.

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From the Institute of Cardiology, Jagiellonian University, Krakow, Poland.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted May 16, 2016, provisional acceptance given July 7, 2016, final version accepted July 11, 2016.

Address for correspondence: Pawel Kleczynski, MD, PhD, Institute of Cardiology, University Hospital, Kopernika 17 Street, 31-501 Krakow, Poland. Email: kleczu@interia.pl