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Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, GermanyDZHK - German Centre for Cardiovascular Research, partner site Munich, Munich, Germany
Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, GermanyDZHK - German Centre for Cardiovascular Research, partner site Munich, Munich, Germany
Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, GermanyDZHK - German Centre for Cardiovascular Research, partner site Munich, Munich, Germany
Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, GermanyDZHK - German Centre for Cardiovascular Research, partner site Munich, Munich, Germany
Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, GermanyDZHK - German Centre for Cardiovascular Research, partner site Munich, Munich, Germany
Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, GermanyDZHK - German Centre for Cardiovascular Research, partner site Munich, Munich, Germany
Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, GermanyDZHK - German Centre for Cardiovascular Research, partner site Munich, Munich, Germany
Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, GermanyDZHK - German Centre for Cardiovascular Research, partner site Munich, Munich, Germany
1 Joerg Hausleiter and Simon Deseive contributed equallyAll authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Joerg Hausleiter
Footnotes
1 Joerg Hausleiter and Simon Deseive contributed equally 1 All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Affiliations
Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, GermanyDZHK - German Centre for Cardiovascular Research, partner site Munich, Munich, Germany
1 Joerg Hausleiter and Simon Deseive contributed equallyAll authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Simon Deseive
Correspondence
Corresponding author at: Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, Germany
1 Joerg Hausleiter and Simon Deseive contributed equally 1 All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Affiliations
Department of Cardiology, Munich University Clinic, Ludwig-Maximilians University, Munich, GermanyDZHK - German Centre for Cardiovascular Research, partner site Munich, Munich, Germany
1 Joerg Hausleiter and Simon Deseive contributed equallyAll authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Prevalence of relevant aortic stenosis in nonagenarians will constantly increase.
•
Transcatheter aortic valve replacement (TAVR) procedure is safe and feasible in patients aged 90 years or older.
•
2-year survival of the nonagenarian group was comparable to the general population.
•
TAVR appears to be a reasonable treatment option in carefully selected patients.
Abstract
Background
In the aging western societies, an increasing prevalence of severe, symptomatic aortic stenosis is observed. The aim of this study was to examine the safety and efficacy of transcatheter aortic valve replacement (TAVR) in patients aged 90 years and older.
Methods
All patients with severe symptomatic aortic stenosis undergoing TAVR at LMU Munich-University-Hospital between 2013 and 2018 were included. Procedure-related mortality (<30 days) was defined as the primary endpoint and survival rates at two years, device failure, and procedural complications were defined as secondary endpoints according to the Valve Academic Research Consortium II criteria.
Results and Conclusions
Out of 2336 patients, 2183 were younger than 90 years (<90y.-group) and 153 patients were aged 90 or older (≥90y.-group). Procedure-related mortality (3.6% <90y.-group vs. 3.3% ≥90y.-group, log-rank p=0.9) and device success (97.2% <90y.-group vs. 96.0% ≥90y.-group, p=0.44) were similar. Estimated survival rates at 2 years were 62.8% (95% CI 55.3 and 71.4) in the elder and 76.0% (95% CI 74.1 and 77.8) in the younger patients (p<0.01). The incidence of acute kidney injury, stroke, major bleeding, and permanent pacemaker implantations were comparable between both groups.
TAVR procedure is equally safe and feasible in patients aged 90 years or older compared to younger patients. Differences in 2-year survival appear to be patient-related rather than procedure-related.
The constant increase in life expectancy in western societies comes along with an increasing prevalence of patients with severe symptomatic aortic stenosis (AS) [
]. In elderly patients with a high perioperative risk, surgical valve replacement is not regarded a feasible therapeutic option. Mortality risk for surgical aortic valve replacement reaches 10.75% in 90-year-old patients and 14.41% in 95-year-olds in otherwise completely healthy patients without any comorbidities [
Transcatheter aortic valve replacement (TAVR) is a causal treatment option for patients with symptomatic AS and a high perioperative risk. While younger AS patients undergoing TAVR frequently present in considerably worse condition due to comorbidities, older AS patients often present in a remarkably good physical and mental condition demanding maximal therapy [
]. Taking into account age-specific risk factors such as increasing frailty or multimorbidity, nonagenarians can be considered a unique population needing further careful investigation [
The impact of frailty status on clinical and functional outcomes after transcatheter aortic valve replacement in nonagenarians with severe aortic stenosis.
So far, only very few studies have explored the safety of TAVR in nonagenarians with several limitations: the number of patients included was not large enough to reflect real-world data [
With a rising life expectancy worldwide, assessing economical and ethical aspects of patient treatment in their final life-years becomes more important [
]. The aim of this study was to examine the safety and efficacy of TAVR in patients aged 90 or older in a large German cohort, with a special focus on procedure-related mortality, procedural feasibility, and long-term outcome of patients.
Methods
Study population
All consecutive patients who underwent TAVR for severe symptomatic AS at LMU Munich University Hospital between January 2013 and December 2018 were included in this analysis (Fig. 1). The decision for TAVR was made by an interdisciplinary “heart-team”, consisting of cardiologists, interventional cardiologist, and cardiothoracic surgeons based on clinical findings, laboratory tests, echocardiography, and contrast-enhanced computer tomography as well as the patient's wish. In addition, nonagenarians were carefully evaluated for cognitive state, life expectancy, and life quality.
All procedural data were collected prospectively as part of the EVERY-TAVI-Registry (ClinicalTrials.gov Identifier: NCT02289339) and all perioperative examinations were part of the routine procedures for TAVR patients at our center. All patients were contacted for a follow-up 30 days after the procedure and at yearly intervals thereafter. Informed consent was obtained from each patient and the study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution's human research committee.
Procedural data
All patients underwent transfemoral TAVR in conscious sedation. All kinds of valves used in our clinical routine were implanted, including non-balloon expandable (CoreValve, Medtronic, Minneapolis, MN, USA and Lotus Valve System, Boston Scientific, Natick, MA, USA) or balloon-expandable prostheses (Edwards SAPIEN XT and S3, Edwards Lifesciences, Irvine, CA, USA). Suture-mediated vascular closure systems (one Prostar XL or two ProGlide systems, Abbott Vascular Inc., Santa Clara, CA, USA) were used for closing of femoral arteries after puncture. During TAVR, heparin or bivalirudin for thrombosis avoidance and intravenous antibiotics for endocarditis prevention were applied. After TAVR, either dual anti-platelet therapy with acetylsalicylic acid (lifelong) and clopidogrel (for at least 3 months) or oral anticoagulation (if indicated by comorbidities) was recommended.
Endpoint definitions
Procedure-related mortality within 30 days was defined as the primary endpoint. Device success was achieved when no device failure defined by aortic annulus rupture, conversion to surgery, peri-procedural death, or aortic regurgitation >I° occurred. Device success was defined as a secondary efficacy endpoint. Other secondary safety endpoints were defined in accordance with the Valve Academic Research Consortium 2 Criteria (VARC-2) criteria and included mortality at 2 years, stroke, need for permanent pacemaker implantation, acute kidney injury (AKI), major or life-threatening bleeding, or peri-procedural myocardial infarction [
Patients were divided into two groups according to their age (<90 years and ≥90 years). Continuous variables are presented as mean ± standard deviation or median with interquartile ranges as appropriate and were compared with the Student's t-test or Wilcoxon rank-sum test. Categorical variables are presented as counts (%) and compared by Fisher's exact test. Survival estimates are based on the Kaplan-Meier method. A two-sided p-value <0.05 was considered statistically significant. Statistical analysis was performed using RStudio, version 1.2.5033 (RStudio Inc., Boston, MA, USA) [
]. Survival rates in the general population were obtained from the Federal Statistical Office of Germany (https://www.destatis.de).
Results
Patients
All patients undergoing TAVR for severe, symptomatic AS at our institution between January 2013 and December 2018 were included. Of 2336 patients who underwent TAVR during this period, 2183 patients (93.4%) were younger than 90 years (<90y-group) and 153 patients (6.6%) were aged 90 years or older (≥90y.-group) at the time of TAVR procedure.
Comparing the baseline characteristics, nonagenarians had a significantly higher Society of Thoracic Surgeons (STS) risk score [3.68 (IQR 2.0–6.0) <90y.-group vs. 7.49 (IQR 5.0–10.1) ≥90y.-group, p<0.001] and lower body mass index (BMI) than younger patients [25.9 (IQR 23.4–29.1) <90y.-group vs. 24.6 (IQR 21.6–26.8) kg/m2 ≥90y.-group, p<0.001]. While gender distribution was almost even in the entire study population (49.9% vs. 50.1%), there were significantly more women in the nonagenarian cohort (48.7% female <90y.-group vs. 69.3% female ≥90y.-group, p<0.001). There was a significantly worse kidney function evaluated by estimated glomerular filtration rate among nonagenarian compared to younger patients [45.6 (IQR 34.2-57.8) <90y.-group vs. 38.6 (IQR 30.5-48.6) ≥90y.-group, p<0.001].
Moreover, the younger patients group showed a numerically higher rate of prior bioprosthesis implantation (5.8% vs. 2.6%, p=0.1) or history of cardiac surgery (14.1% vs. 8.5%, p=0.1), however, without statistical significance. The only cardiovascular risk factor with a significant difference between both groups was (past or active) smoking, which was less common among older patients (21.2% <90y.-group vs. 11.3% ≥90y.-group, p=0.003). All baseline characteristics are shown in Table 1.
Table 1Baseline characteristics.
Total population(n=2336)
< 90 Years(n=2183)
≥ 90 Years(n=153)
p-value
Age (in years)
81.3 (77.0–85.6)
80.8 (76.7–84.7)
92.1 (90.9–93.1)
<0.001
Gender
<0.001
- male
49.9% (1167)
51.3% (1120)
30.7% (47)
- female
50.0% (1169)
48.7% (1063)
69.3% (106)
STS-score
4.0 (2.7–7.5)
3.7 (2.0–6.0)
7.5 (5.0–10.1)
<0.001
BMI
25.8 (23.2–28.9)
25.9 (23.4–29.1)
24.6 (21.6–26.8)
<0.001
Aortic valve mean gradient (in mmHg)
36.0 (26.0–46.0)
36.0 (26.0–45.0)
37.0 (26.0–47.5)
0.55
Aortic valve opening area (in cm²)
0.75 (0.6–0.9)
0.75 (0.6–0.9)
0.7 (0.5–0.8)
<0.001
LV function
0.72
- Normal
67.6% (1577)
67.6% (1476)
66.0% (101)
- Slightly impaired
10.9% (256)
10.8% (236)
13.1% (20)
- Moderately impaired
15.5% (360)
15.5% (338)
14.4% (22)
- Severely impaired
6.1% (143)
6.1% (133)
6.5% (10)
Cardiovascular risk factors:
History of
- Hypercholesterolemia
46.2% (1082)
46.7% (1019)
41.2% (63)
0.08
- Hypertension
91.3% (2132)
93.1% (1985)
90.8% (147)
0.09
- Smoking
20.5% (479)
21.2% (462)
11.3% (17)
0.003
- Diabetes
31.9% (746)
32.4% (708)
25.0% (38)
0.06
- Positive family history for vascular disease
10.0% (234)
10.3% (226)
5.9% (8)
0.16
Renal function
- GFR at baseline (ml/min)
45.1 (33.9–57.2)
45.6 (34.2–57.8)
38.6 (30.5–48.6)
<0.001
- impaired renal function
79.5% (1832)
78.9% (1700)
87.4%(132)
0.01
(GFR <60 ml/min)
- dialysis
4.2% (99)
4.4% (96)
2.0% (3)
0.21
Coronary artery disease
63.7% (1490)
64.7% (1133)
64.8% (100)
0.86
History of
- Revascularization
39.4% (920)
40.0% (873)
30.8% (47)
0.03
- PCI
35.4% (827)
35.9% (783)
28.1% (44)
0.06
- CABG
10.0% (235)
10.3% (224)
6.8% (11)
0.2
- Myocardial Infarction
16.8% (393)
17.1% (373)
13.1% (20)
0.25
Atrial fibrillation
28.6% (674)
28.8% (629)
29.4% (45)
0.85
Prior bioprosthesis
5.6% (132)
5.8% (128)
2.6% (4)
0.1
History of cardiac surgery
13.7% (321)
14.1% (308)
8.5% (13)
0.05
BMI, body mass index; CABG, coronary artery bypass graft; GFR, glomerular filtration rate; LV, left ventricular; PCI, percutaneous coronary intervention; STS-score, Society of Thoracic Surgeons risk score.
Balloon-expandable valves were used in the majority of patients in this analysis (81.3%) and were less frequently used in nonagenarians (74.5 vs. 81.8%, p=0.03). Smaller prostheses were more commonly used among nonagenarians (prosthesis sizes compared in <90y.-group vs. ≥90y.-group: <25 mm-prosthesis: 30.6% vs. 46.4%, 25–28 mm-prosthesis: 43.1% vs. 40.4%, and >28 mm-prosthesis: 26.3% vs. 13.2%, p<0.001). Pre- and postdilatation was done equally often in both groups (predilatation: 78.4% <90y.-group vs. 77.8% ≥90y.-group, p=1; postdilatation: 5.2% <90y.-group vs. 5.8% ≥90y.-group, p=0.71). There was a trend for higher rates of concomitant percutaneous coronary intervention in the TAVR procedure amongst older patients (11.7% vs. 17.0%, p=0.07). All procedural data are shown in Table 2.
Procedure-related 30-day mortality (3.6% <90y.-group vs. 3.3% ≥ 90y.-group) did not differ between groups (log-rank p=0.9, Fig. 2). However, long-term survival was significantly different (log-rank p-value <0.001). Estimated survival rates at 2 years were 62.8% (95% CI 55.3 and 71.4) in nonagenarians and 76.0% (95% CI 74.1 and 77.8, p=0.03) in the younger patients. For comparison with the general population, 2-year survival rates of the general population were calculated for a cohort of 92-year old patients consisting of 69.3% females and 81-year old patients consisting of 48.7% females. This resulted in 2-year survival rates in the general population of 62.0% and 87.7% respectively (see also Fig. 3). Death from cardiac causes did not differ between both groups (8% <90y.-group vs. 7.9% ≥ 90y.-group, log-rank p=0.4, Online Fig. 1). A summary of death causes is presented in Online Table 1 and all deaths occurring within the first 30 days after TAVR are listed in Online Table 2.
Fig. 2Death from any cause within the first 30 days after transcatheter aortic valve replacement. Cumulative incidence curves for the occurrence of the primary study endpoint (all-cause mortality at 30 days) are shown for nonagenarians (blue curve) and younger patients (green curve).
Fig. 3Survival on long-term follow-up. Survival curves are shown for nonagenarians (blue curve) and younger patients (green curve). The black dashed line illustrates the survival in the general population in Germany (92 years old, 69.3% women) for comparative purposes.
Comparable rates of device success were achieved in both groups (97.2% <90y.-group vs. 96.0% ≥90y.-group, p=0.44). Periprocedural strokes (1.5% <90y.-group vs. 2.6% ≥90y.-group, p=0.3), the need for permanent pacemaker implantation (17.1% <90y.-group vs. 18.3% ≥90y.-group, p=0.74) and the occurrence of AKI (12.8% <90y.-group vs. 11.9% ≥90y.-group, p=0.89) did not differ between both groups. The median Hb-drop was 1.6 (IQR: 0.9-2.3) g/dl without significant differences between both groups [1.6 (IQR 0.9-2.3) <90y.-group vs. 1.7 (IQR 1.0-2.5) ≥90y.-group, p=0.24]. Major or life-threatening bleeding events as defined by the VARC-2 criteria occurred at similar rates in both groups (11.8% <90y.-group vs. 10.7% ≥90y.-group, p=0.79). There was no significant difference in relevant aortic valve regurgitation after valve implantation (1.6% <90y.-group vs. 3.3% ≥90y.-group, p=0.18). All procedural outcomes are presented in Table 3. For odds ratios, see Fig. 4. Assessment of New York Heart Association (NYHA) class before and after TAVR revealed a significant improvement in functional status in nonagenarians (p<0.001, Fig. 5).
Table 3Procedural outcome.
Total population(n=2336)
< 90 Years(n=2183)
≥ 90 Years(n=153)
p-value
Device success
97.2% (2297)
97.2% (2122)
96% (147)
0.44
Procedural death
0.6% (15)
0.6% (14)
0.7% (1)
1
Relevant regurgitation
1.7% (40)
1.6% (35)
3.3% (5)
0.18
Prosthesis dislocation
0.8% (19)
0.8% (17)
1.3%(2)
0.35
Annulus rupture
0.6% (13)
0.6% (13)
0.0% (0)
0.69
Pericardial effusion
1.4% (33)
1.5% (32)
0.6% (1)
0.72
TAVR conversion to surgery
0.5% (11)
0.5% (11)
0.0% (0)
1
New pacemaker
17.2% (402)
17.1% (374)
18.3% (28)
0.74
Periprocedural stroke
1.6% (37)
1.5% (33)
2.6% (4)
0.3
Periprocedural myocardial infarction
0.8% (18)
0.8% (18)
0% (0)
0.63
Postprocedural acute kidney injury
12.7% (293)
12.8% (275)
11.9% (18)
0.89
Vascular complications (VARC-2 major bleeding or life-threatening bleeding)
11.7% (269)
11.8% (253)
10.7% (16)
0.79
Periprocedural Hb-drop (in g/dl)
1.6 (0.9–2.3)
1.6 (0.9–2.3)
1.7 (1.0–2.5)
0.24
Mortality at 30 days
3.6% (84)
3.6% (79)
3.3% (5)
0.9
Stroke at 30 days
3.0% (71)
2.9% (63)
5.2% (8)
0.14
TAVR, transcatheter aortic valve replacement; VARC-2, Valve Academic Research Consortium-2.
Fig. 4Incidence of procedural complications in nonagenarians compared to younger patients. Odds ratios for relevant transcatheter aortic valve replacement-related complications in nonagenarians compared to younger patients. VARC-2, Valve Academic Research Consortium-2.
Fig. 5NYHA functional class before and after TAVR in nonagenarians. The percentages of patients in different NYHA functional status before and after TAVR. NYHA, New York Heart Association; TAVR, transcatheter aortic valve replacement.
In this analysis, TAVR appears to be equally feasible and safe in patients aged 90 years or older compared to younger patients, with regard to early procedure-related mortality, device success, and other relevant procedural complications, including the need for permanent pacemaker implantation, strokes, bleeding events, and AKI.
The constantly increasing standard of medical care, novel medical therapies, and healthier lifestyles lead to a worldwide trend of rising life expectancy [
]. In Germany, as in most western societies, the demographic change is ongoing and results in fewer young people and more old people. With aging societies, the prevalence of medical conditions such as degenerative AS increases [
]. This will result in a higher prevalence of severe, symptomatic AS requiring valvular replacement therapy, and underlines the necessity and importance of investigating the safety and efficacy of TAVR in elderly patients. To date, a couple of other studies focused on the outcome of nonagenarians undergoing TAVR. Most of those studies are, however, limited by very low numbers of patients enrolled and/or very short follow-up periods [
The impact of frailty status on clinical and functional outcomes after transcatheter aortic valve replacement in nonagenarians with severe aortic stenosis.
Survival rates in older patients are naturally lower than in a younger population and have to be interpreted with respect to similar studies and the overall mortality of the general population of the same age. In the largest study, Arsalan et al. investigated the safety and efficacy of TAVR in 24,025 patients, of whom 3773 (15.7%) were 90 years or older. The authors showed a significantly higher 1-year mortality rate among older patients. 1-year survival reported in other studies including at least 80 nonagenarians ranged from 69.1% to 87.5% and was comparable to our analysis [
]. Although our study is smaller, this study is the first to investigate 2-year survival in more than 150 nonagenarians, and more procedural endpoints were analyzed including devices success, acute kidney failure, and the need for pacemaker implantation.
Before the era of TAVR, patients with severe AS deemed inoperable were left to medical treatment alone. In an analysis by Kojodjojo et al., patients with severe AS (mean age 87.2 years) deemed inoperable had a survival rate below 30% after 2 years [
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.
]. In patients considered operable (mean age 83.6 years) but refusing surgical valve replacement, survival rates were below 50% after 2 years. Nonagenarians in our analysis (median age 92.1 years) had a survival rate well above 60%, which was similar to the average survival rate of the general nonagenarian population in Germany. In contrast, the group of younger patients had a lower survival rate when compared to the general population. In addition, despite being older, the rate of cardiac death was not higher in the nonagenarian group. Thus it is likely, that patients in the nonagenarian group were rather healthy despite having severe AS. Taken together, these observations and considerations suggest a benefit of TAVR in carefully selected nonagenarians. Age alone should not be a contraindication for TAVR, but randomized data are warranted to confirm this hypothesis.
Limitations
This study is not without limitations. An analysis comparing nonagenarians to younger patients is probably susceptible to a relevant selection bias resulting in some heterogeneity of comorbidities, which needs to be taken into account when interpreting the data. However, compared to other studies, this was less pronounced in this analysis [
]. Furthermore, our data reflect a single-center experience and (apart from evaluation of NYHA class evaluation after TAVR) no quality of life measures or dedicated geriatric frailty scores were obtained to demonstrate symptomatic improvement of patients or assess the overall frailty of patients.
Conclusion
In this analysis, TAVR procedure was found to be equally safe and feasible in patients aged 90 years or older compared to younger patients. Differences in 2-year survival appear to be patient-related rather than procedure-related. Regarding the overall 2-year survival rate of nearly 63% in those patients, which was comparable to the general population, TAVR seems a reasonable treatment in carefully selected patients aged 90 years or older with severe, symptomatic AS and patients should not be excluded from treatment solely because of their age.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration Of Competing Interest
Prof. Mehilli has received an institutional research grant from Boston Scientific; lecture fees from Edwards Lifesciences, Medtronic, Biotronik, Terumo, Boston Scientific, BMS, and Astra Zeneca. Prof. Hausleiter has received speaker honoraria, research support, and serves on the advisory board for Abbott Vascular and Edwards Lifesciences. Dr Braun has received speaker honoraria from Abbott Vascular. The other authors have declared no conflicts of interests.
The impact of frailty status on clinical and functional outcomes after transcatheter aortic valve replacement in nonagenarians with severe aortic stenosis.
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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