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Transcatheter aortic valve replacement for severe aortic stenosis can improve long-term survival of nonagenarians as compared to an age- and sex-matched general population
Corresponding author at: Department of Cardiology, Cardiovascular Center Bad Neustadt, Salzburger Leite 1, D - 97616 Bad Neustadt a. d. Saale, Germany.
Same long-term survival after transcatheter aortic valve replacement (TAVR) in nonagenarians compared to general population.
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Negative prognostic impact of severe aortic valve stenosis in nonagenarians was eliminated by TAVR.
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TAVR is a valuable treatment even in very elderly patients after careful selection.
Abstract
Background
Nonagenarians are at increased risk for morbidity and mortality after transcatheter aortic valve replacement (TAVR) based solely on their age.
The aim of our study was to evaluate survival of nonagenarians with severe aortic valve stenosis (AS) after TAVR as compared to an age- and sex-matched general population.
Methods
From 2009 to 2017, 1052 consecutive patients ≥80 years scheduled for TAVR were included. Patients were divided into three groups depending on their age at the time of the procedure: 80–84 (Group 1), 85–89 (Group 2) and ≥90 years (Group 3). Survival of patients treated with TAVR was compared to the life expectancy of an age- and sex-matched cohort in the general population.
Results
Nonagenarians were more likely to experience major access-site complications than their younger counterparts (7.6% Group 1 vs. 10.1% Group 2 vs. 17.6% Group 3, p = 0.016). One-year mortality in nonagenarians was higher as compared to the general population (27.8% vs. 20.0%). After two years, the mortality curves between the TAVR patients and the general population converged (39.2% vs. 37.5%) and were lower after five years.
Conclusions
During the observation period of five years, carefully selected nonagenarians treated with TAVR had at least the same mortality rate as an age- and sex-matched general population after two years despite procedure-associated complications. The negative prognostic impact of the severe AS was completely eliminated by TAVR.
With the introduction of transcatheter aortic valve replacement (TAVR), cardiovascular medicine is undergoing a dramatic paradigm shift in the way aortic valve stenosis (AS) is treated. Over the past 10 years, this therapy has become a viable treatment option for patients with severe AS who are at high surgical risk [
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.
Guidelines on the management of valvular heart disease (version 2012): the joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).
]. Factors increasing risk for poor outcomes after TAVR are commonly less present in nonagenarians as compared to the younger population. These patients are at increased risk for morbidity and mortality after TAVR simply based on their age [
]. Because of their shortened and difficult predictable life expectancy, decision-making for TAVR in nonagenarians is complicated in daily practice. The primary concern is that nonagenarians might not survive and recover from the procedure as frequently as younger patients. The effect and outcome of TAVR in nonagenarians in terms of complications and mortality is a matter to investigate since they represent only a small fraction of patients enrolled in the vital clinical trials. There are not enough data for TAVR in very elderly patients regarding long-term survival. To address this clinically relevant question whether TAVR in nonagenarians is not only feasible but also reasonable we compared the survival of nonagenarians after TAVR using the Kaplan-Meier estimates to an age- and sex-matched general population in Germany [
From 2009 to 2017, all patients aged at least 80 years scheduled for TAVR were entered into a database. Patient selection was based on current guidelines. Decision-making for TAVR was made by an interdisciplinary heart team consisting of an interventional cardiologist and a cardiac surgeon. Patients were divided into three groups depending on their age at the time of the procedure: 80–84 (Groups 1), 85–89 (Group 2), and ≥90 years (Group 3). The survival function of all patients who underwent TAVR in our institution was calculated over full data and evaluated at indicated times (one to five years).
Definition of general population and methodology
The general population includes all persons resident in Germany in 2009. Data for the general population were generated from the Statistical Yearbook of the Federal Republic of Germany from the year 2009 [
]. Among other demographics, the health statistic collects and analyzes data on the state of health and death of the population in Germany.
Observed mortality rates for the general population were obtained from the mortality table of the Federal Statistics Office of the Federal Republic of Germany from 2009. This is a demographic model that provides an aggregated assessment of the mortality rates of the German population. Additionally, the mortality table provides information on the gender-specific average life expectancy in each age group [
]. In our study, only data of patients aged 80 years and above have been taken into account. Finally, the estimated mortality rates of the patients treated with TAVR were compared to the expected mortality of the general population. Thereby, the data were adjusted according to age and gender for each patient. Further details about the calculation of the mortality table can be found in the publication of the German Federal Statistics Office [
Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience.
]. We used a balloon-expandable valve Edwards Sapien XT (Edwards Lifescience, Irvine, CA, USA) until 2014 and thereafter the next-generation balloon-expandable prosthesis SAPIEN S3. As self-expanding valves the ACURATE, ACURATE TA™, and ACURATE neo™ (Boston Scientific, Natick, MA, USA), and the Medtronic CoreValve® and CoreValve® EvolutR™ bioprosthesis (Medtronic, Irvine, CA, USA) were used. Procedures were performed by transfemoral (TF) approach in a hybrid operating room as the first choice under general anesthesia or in exceptional cases under local anesthesia and deep sedation. When the TF approach was not feasible because of unsuitable vascular access (e.g. prohibitive calcification, undersized vessels, or with relevant iliofemoral atherosclerotic disease) transapical (TA) and direct aortic (DA) approach (in two cases) were performed as potential alternatives. All procedures were performed under fluoroscopic guidance and peri-procedural transesophageal echocardiography (TEE) was used when general anesthesia (GA) was applied.
Data collection
Baseline and procedural characteristics and post-interventional course were documented prospectively in a standardized electronic documentation form. Laboratory results were imported electronically for classification of bleeding and acute kidney injury. The diagnostic work-up included transthoracic echocardiography, coronary angiography, and multislice computed tomography (CT) of the aorta, as previously described [
Diagnostic accuracy of computed tomography angiography for the detection of coronary artery disease in patients referred for transcatheter aortic valve implantation.
]. CT data of all patients were analyzed to determine the dimensions of the aortic annulus using semi-automated software (3mensio Structural Heart™; Pie Medical Imaging BV, Maastricht, the Netherlands) incorporated into our program in 2014. All cases of suspected stroke were investigated by our onsite Neurology Department, including cerebral CT or magnetic resonance imaging (MRI), and confirmed or discarded. Before patient discharge, post-interventional mean gradient and the extent of regurgitation of the aortic prosthesis were determined by echocardiography. Survival status was determined by follow-up telephone calls at 30 days and yearly thereafter. Analysis was conducted according to the definitions of the Valve Academic Research Consortium-2 consensus document (VARC-2 criteria) and included stroke, major vascular and bleeding complications, paravalvular leakage (PVL), and device success, the later defined as the composite end point consisting of absence of 30-day mortality, correct positioning of a single prosthesis, and prosthesis performance [
]. Procedural characteristics and clinical outcomes were compared in patients among the three subgroups. Analysis of patient data for scientific evaluation is permissible by federal law and review of patient data was approved by our institutional ethics committee.
Statistical analysis
Quantitative variables were expressed as mean ± standard deviation. Qualitative data (nominal or ordinal scale) were given as frequencies. For comparison between subgroups, chi-square-test was used for categorical variables and the Man-Whitney-Wilcoxon test for continuous variables. A p-value <0.05 was considered significant. All-cause-mortality analysis was performed by the Kaplan-Meier method. Statistical analysis was performed with IBM SPSS Statistics for Windows, Version 24.0 (IBM Corp., Armonk, NY, USA).
Results
Patient characteristics
Between 2009 and 2017, 1052 consecutive patients with an age of at least 80 years were scheduled for TAVR. The mean age was 84.0 ± 3.2 years and the mean body mass index (BMI) 27.4 ± 4.7 kg/m2; 57.4% (604/1052) were female. The estimated mean logistic EuroSCORE I was 19.6 ± 13.3. Groups did not differ in sex distribution, comorbidities such as diabetes, hypertension, chronic obstructive lung disease (COLD), atrial fibrillation (AF), stroke, prior cardiac surgery, percutaneous coronary intervention (PCI), and left ventricular ejection fraction (LVEF). Compared to patients under the age of 90 years, nonagenarians had a lower BMI (27.9 ± 4.8 vs. 26.7 ± 4.3 vs. 25.4 ± 4.6, p < 0.001) and a higher estimated surgical mortality (log. EuroSCORE I, 17.9 vs. 21.6 vs. 25.8, p < 0.001) (Table 1).
Table 1Baseline characteristics.
Demographics
80–84 years n = 658
85–89 years n = 326
≥90 years n = 68
p-value
Age, mean, yrs
81.9 ± 1.4
86.6 ± 1.4
91.3 ± 1.2
<0.001
Sex, female, n (%)
378/658 (57.4)
188/326 (57.7)
38/68 (55.9)
0.964
Body-Mass-Index (kg/m2)
27.9 ± 4.8
26.7 ± 4.3
25.4 ± 4.6
<0.001
Comorbidities
Diabetes mellitus, n (%)
210/649 (32.4)
83/321 (25.9)
16/67 (23.9)
0.226
Hypertension, n (%)
591/649 (91.1)
284/321 (88.5)
57/67 (85.1)
0.405
COLD, n (%)
62/658 (9.4)
28/326 (8.6)
5/68 (7.4)
0.805
Atrial fibrillation, n (%)
173/648 (26.7)
81/319 (25.4)
23/67 (34.3)
0.802
Stroke, n (%)
80/649 (12.3)
33/321 (10.3)
6/67 (9.0)
0.513
Prior cardiac surgery, n (%)
68/610 (11.1)
28/303 (9.2)
3/63 (4.8)
0.229
Prior PCI, n (%)
195/649 (30.0)
94/321 (29.3)
19/67 (28.4)
0.941
Preoperative dialysis, n (%)
14/649 (2.2)
4/320 (1.3)
0/67 (0.0)
0.317
NYHA Functional Class II-IV, n (%)
593/649 (91.4)
292/321 (91.0)
65/67 (97.0)
0.085
Aortic valve insufficiency >1°, n (%)
90/658 (13.6)
38/326 (11.7)
10/68 (14.7)
0.927
Logistic EuroSCORE, mean
17.9 ± 13.1
21.6 ± 13.2
25.8 ± 13.1
<0.001
LVEF, mean
53 ± 14
53 ± 13
51 ± 14
0.331
LVEF <35%, n (%)
45/657 (6.8)
21/326 (6.4)
5/67 (7.5)
0.809
Valve-in-valve, n (%)
16/652 (2.5)
8/325 (2.5)
1/68 (1.5)
0.975
Values are mean ± SD. Values in parentheses are percentages.
COLD, chronic obstructive lung disease; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; NYHA, New York Heart Association.
In-hospital-outcome and procedural data are presented in Table 2. The transfemoral approach was the preferred access route with no significant difference in all three groups (65.2% vs. 60.1% vs. 64.7%, p = 0.292). All three groups were homogeneous with respect to procedure time, pre-and post-interventional time, the stay in Intensive Care Unit (ICU), and Intermediate Care Unit (IMCU). The number of implanted pacemakers, intra-procedural cardiopulmonary resuscitations (CPR), and the occurrence of ventricular fibrillation (VF) did not differ between the three groups. The necessity for valve-in-valve implantation occurred more frequently in group three (2.6% vs. 2.8% vs. 4.4%, p = 0.681). The incidence of a post-procedural atrioventricular block III° was significantly higher in the second group (85.0–89.9 years) as compared to other groups (10.2% vs. 17.5% vs. 10.3%, p = 0.004).
Table 2In-hospital-outcome and procedure characteristics.
80–84 years n = 658
85–89 years n = 326
≥90 years n = 68
p-value
Transfemoral approach, n (%)
429/658 (65.2)
196/326 (60.1)
44/68 (64.7)
0.292
Procedure time (min)
71 ± 45
76 ± 49
74 ± 38
0.246
Fluoroscopy time (min)
8.9 ± 9.7
10.8 ± 44.3
8.4 ± 5.3
0.541
Contrast agent (ml)
117 ± 126
106 ± 60
110 ± 63
0.314
Area dosage (cGy*cm2)
5263 ± 6284
5301 ± 9049
4801 ± 3706
0.866
Length of stay, days
17.8 ± 12.9
19.1 ± 13.9
19.4 ± 10.4
0.278
Length of stay pre-interventional, days
5.3 ± 4.7
5.8 ± 5.2
6.0 ± 6.9
0.175
Length of stay post-interventional, days
12.6 ± 11.7
13.4 ± 12.1
13.4 ± 7.5
0.527
Length of stay in ICU, days
3 ± 11
3 ± 9
2 ± 5
0.748
Length of stay in IMCU, days
7 ± 8
8 ± 9
9 ± 7
0.153
Discharge home, n (%)
116/658 (17.6)
60/326 (18.4)
11/67 (16.4)
0.146
Discharge in rehabilitation facility, n (%)
416/658 (63.2)
190/326 (58.3)
37/67 (55.2)
0.146
Discharge in hospice, n (%)
1/658 (0.2)
0/326 (0.0)
0/67 (0.0)
0.146
Conversion open surgery, n (%)
14/658 (2.1)
7/326 (2.1)
2/68 (2.9)
0.908
Conversion with sternotomy, n (%)
13/658 (2.0)
7/326 (2.1)
1/68 (1.5)
0.935
AV block III°, n (%)
67/658 (10.2)
57/326 (17.5)
7/68 (10.3)
0.004
Pacemaker implantation, n (%)
97/658 (14.7)
71/326 (21.8)
12/68 (17.6)
0.278
TAV-in-TAV, n (%)
17/658 (2.6)
9/326 (2.8)
3/68 (4.4)
0.681
Intraprocedural CPR, n (%)
18/658 (2.7)
12/326 (3.7)
2/68 (1.9)
0.718
Intraprocedural VF, n (%)
23/658 (3.5)
11/326 (3.4)
2/68 (2.9)
0.970
Intra-hospital mortality, n (%)
34/658 (5.2)
21/326 (6.4)
4/68 (5.9)
0.712
Values are mean ± SD. Values in parentheses are percentages.
AV block, atrioventricular block; CPR, cardiopulmonary resuscitation; ICU, intensive care unit; IMCU, intermediate care unit; MPG, mean pressure gradient; TA, transapical; TAV, transcatheter valve; TF, transfemoral; VF, ventricular fibrillation.
Compared with patients under age 90 years, nonagenarians were more likely to experience major access-site complications (7.6% vs. 10.1% vs. 17.6%, p = 0.016) and increased need for blood transfusion (24.1% vs. 32.5% vs. 38.2%, p = 0.003). At 30 days, the composite endpoint of all-cause mortality, stroke, life-threatening bleeding, stage two or three acute kidney injury, coronary obstruction requiring intervention, major vascular complications, or a repeat procedure for valve-related dysfunction occurred more frequently in nonagenarians as compared to the patients under age 90 years (13.5% vs. 17.5% vs. 27.9%, p = 0.004). Further details are shown in Table 3.
In all three groups, estimated survival rates at 30 days and after 1,2,3,4, and 5 years decreased with age and time and reached the lowest value in nonagenarians (survival after 5 years, 47.0% vs. 42.0% vs. 40.8%) (Fig. 1a–c). In patients aged 80–84 years, the estimated survival rates were lower during the complete follow-up as compared to age- and sex-matched general population (one-year survival rate 82.4% vs. 92.6%, two-year survival rate 75.7% vs. 84.9%, five-year survival rate 47.0% vs. 52.4%). The incidence of one-year mortality in nonagenarians treated with TAVR was higher as compared to the same age- and sex-matched general population (27.8% vs. 20.0%). After two years, the mortality curves of the TAVR patients and an age- and sex-matched general population converged (39.2% vs. 37.5%) and were even lower after five years (59.2% for the TAVR patients and 74.2% for an age- and sex-matched general population). A comparison of one-year mortality between patients treated with TAVR and patients declined for surgery is provided in Fig. 2. Our patients aged 85–89 years treated with TAVR had a much lower one-year mortality (18%) as compared to patients with severe AS (mean age 89 ± 6 years, aortic valve area 0.6–≤0.8 cm2, logistic EuroSCORE 18.3 ± 14.3%) refusing surgery or rejected due to co-morbidities (31%) [
Outcomes of elderly patients aged 80 and over with symptomatic, severe aortic stenosis: impact of patient’s choice of refusing aortic valve replacement on survival.
] one-year mortality of patients who were considered to be inappropriate candidates for surgery was 50% (mean age 87.2 ± 4.2 years, aortic valve area 0.65 ± 0.19 cm2, logistic EuroSCORE 20.2 ± 13.4%).
Fig. 1(a–c) Age-dependent estimated mortality rates of all patients treated with transcatheter aortic valve replacement compared to an age- and sex-matched general population.
Fig. 2Comparison of one-year mortality between patients treated with transcatheter aortic valve replacement (TAVR) (A) vs. patients declined for surgery (B, C).
Advanced age is the strongest predictor of death. The number of patients aged 90 years or greater encountered in daily practice is increasing steadily. Clinicians are confronted with an increasing number of nonagenarians with severe aortic valve stenosis. In nonagenarians overall life expectancy is reduced and difficult to predict. Therefore, informed clinical decision-making for administering TAVR to nonagenarians is complicated in daily practice. The key question is what the life expectancy of these patients would be if left "untreated". To the best of our knowledge, there are no randomized, prospective datasets for nonagenarians to report to date.
In our study, advanced age and in-hospital complications resulted in a worse short- and mid-term outcome in nonagenarians in contrast to younger patients (80–89 years). The French National Transcatheter Aortic Valve Implantation Registry (FRANCE-2) and the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) reported a 30-day mortality rate of 11.2% and 8.8% in nonagenarians [
]. These results are in line with our findings (10.3% 30-day mortality rate in nonagenarians). Similar to the results of Arsalan et al. and Yamamoto et al., our data showed an increasing prevalence of major vascular complications in very old patients (over 90 years), but no significant differences in minor vascular injury rates as compared to younger patients [
]. In our study, the increased incidence of these major vascular complications is reflected in a decreased early safety at day 30 according to the VARC-2 criteria.
In contrast to the FRANCE-2 and STS/ACC TVT registry [
], which had a survival follow up of only one year, we evaluated the survival of our octogenarians and nonagenarians for over 5 years. Additionally, we compared the survival rate of our patients treated with TAVR with the life expectancy of the general population. For this purpose we used the mortality table of the Federal Republic of Germany after adjusting for gender and age. This table shows the all-cause mortality of the German population for the respective year. Comparing the estimated one-year mortality rate in our octogenarians and nonagenarians treated with TAVR to an age- and sex-matched general population, survival was slightly decreased in all three groups [
]. These findings were mainly caused by procedure-associated complications as mentioned above. In the group of 80–84-year-old patients, the initially increased mortality rate within the first year was balanced out afterwards resulting in a parallel survival curve as compared to the life expectancy of the general population over the next four years. In contrast to the 80–84 year old patients, the survival curves of patients aged 85–89 years and nonagenarians and the survival curve of the age- and sex-matched general population met each other after one year. Thus, the negative prognostic impact of the severe AS in our selected nonagenarians was completely eliminated by TAVR. This finding was unexpected especially in nonagenarians. The higher logistic EuroSCORE of the nonagenarians as compared to the octogenarians was mainly caused by the advanced age, which disproportionately influenced the risk assessment. The prognosis of our nonagenarians was mainly driven by the severe AS. These findings are in line with previous studies, which also demonstrate beneficial outcomes of nonagenarians after TAVR with prolonged survival and improved quality of life [
]. But to achieve such beneficial outcome, a careful patient selection plays a crucial role in nonagenarians due to the higher incidence of major access-site complications resulting in a higher 30-day mortality.
To the best of our knowledge, there are no randomized studies available, which compared very elderly patients treated with TAVR with untreated. Such an approach would be difficult to justify ethically. Therefore, we compared the survival rate of our octogenarians and nonagenarians treated with TAVR with untreated peers with severe AS from earlier publications. Natural history of untreated patients with severe AS was described for example in the studies from Kojodjojo et al. and Murakami et al. The first study included patients who were not fit for surgery and were managed conservatively. In the second study, Murakami et al. enrolled patients refusing aortic valve replacement (AVR) or having contraindications for AVR at the initial diagnosis. Both studies included only a small number of patients. The proportion of nonagenarians in these publications was conspicuously small. Patients without surgical treatment of their severe AS had a slightly lower logistic EuroSCORE including a better left ventricular ejection fraction as compared to our patients. Interventional treatment of the severe AS in our patients aged 85–89 years nearly reduced mortality at least by half within one year despite procedural associated complications in the treated group [
Outcomes of elderly patients aged 80 and over with symptomatic, severe aortic stenosis: impact of patient’s choice of refusing aortic valve replacement on survival.
During the observation period of five years, carefully selected nonagenarians treated with TAVR had at least the same mortality rate as an age- and sex-matched general population after two years. The negative prognostic impact of the severe AS was completely eliminated by TAVR. This unexpected outcome emphasizes the importance of TAVR as a valuable treatment even in very elderly patients after careful selection.
Limitations
Our findings are drawn from the experience of a single center. Our study is not a prospective trial. The number of nonagenarians was relatively small. We have performed TAVR since 2009. Patients aged over 90 years treated with TAVR were included only within the last five years. For this reason, the follow-up time for this patient group is shorter in comparison to the other patients and the confidence interval of the estimated mortality rate had a broad range.
Conflict of interest statement
The authors have no conflicts of interest to declare.
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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.
Guidelines on the management of valvular heart disease (version 2012): the joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS).
Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk: acute and late outcomes of the multicenter Canadian experience.
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Outcomes of elderly patients aged 80 and over with symptomatic, severe aortic stenosis: impact of patient’s choice of refusing aortic valve replacement on survival.
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