ADVERTISEMENT
Efficacy and Safety of Transcatheter Aortic Valve Implantation in Aortic Stenosis Patients With Extreme Age
Abstract: Objectives. To investigate the in-hospital and long-term outcomes of patients at extreme age with severe symptomatic aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI). Methods. A total of 276 consecutive patients with a mean age of 82.2 ± 5.0 years with severe symptomatic AS underwent TAVI at our institute. We evaluated periprocedural, in-hospital, and long-term outcomes in all patients aged ≥87 years (the highest 20th percentile of age distribution) and compared them with the less elderly patients. Results. The extremely aged group included 58 patients (21%) ≥87 years (mean age, 89.0 ± 1.9 years; 67.2% women). Baseline EuroSCOREs and STS scores were 19.6 ± 11.2% and 9.4 ± 5.0%, respectively. Nineteen patients (34.5%) were considered frail. Following TAVI, all patients regained New York Heart Association class 1-2 functional capacity. The main periprocedural and in-hospital complications were minor vascular complications, bleeding requiring blood transfusions, and the need for permanent pacemaker. None of the patients suffered from clinical stroke. In comparison to the less elderly patients, there were no significant differences in the rates of periprocedural, in-hospital complications or long-term survival (log rank, 0.87). Conclusions. Meticulously selected patients at extreme age benefit from TAVI with a reasonable overall risk, which does not impact the overall survival or functional status.
J INVASIVE CARDIOL 2015;27(10):475-480. Epub 2015 July 15
Key words: TAVI, outcome, frailty, extreme age
____________________________________________________
Aortic stenosis (AS) is a frequent valvular heart disease with an increasing prevalence with advanced age.1 Transcatheter aortic valve implantation (TAVI) is becoming the treatment of choice for elderly patients with severe symptomatic AS, and has been offered to very old patients who were previously excluded from valve replacement surgery.2-4
The decision to perform TAVI in very old patients is challenging due to specific issues associated with extreme age (eg, frailty, co-morbidities, and cognitive impairment) that may impact their overall outcome. Currently, little is known about the outcome of patients with extreme age following TAVI. Therefore, we sought to investigate the in-hospital and long-term outcomes of patients with extreme age who underwent TAVI.
Methods
We evaluated 276 consequential patients who underwent TAVI due to severe AS at the Rabin Medical Center between November 2008 and March 2014. Candidates for TAVI were carefully evaluated by a dedicated heart team consisting of interventional cardiologists, echocardiographers, valvular specialists, cardiac surgeons, and an imaging specialist. Vascular surgeon, geriatrician, and others specialists were consulted as needed.
Surgical risk assessment was performed using the Logistic European System for Cardiac Operative Risk Evaluation score (EuroSCORE) I and II7,8 and the Society of Thoracic Surgeons (STS) score.9 Frailty as assessment for post-surgical recovery trajectories was performed using a frailty index that consists of five items:6 (1) body mass index (BMI) <20 kg/m2 and/or unintentional weight loss >5 kg/year; (2) <20th population percentile for grip strength; (3) slowed walking speed on 5 minute walking test; (4) serum albumin <3.5 g/dL; and (5) cognitive impairment or dementia.
The mean age was 82.2 ± 5.0 years with a non-symmetrical distribution (Figure 1). Most patients (68.1%) were between 80-89 years old. In order to represent best the extreme age subgroup in our cohort (and maintain a reasonable population sample size) we chose the upper 20th percentile for age (87 years old) as the cut-off value for our extreme age analysis.
The following data were extracted from our database: (1) baseline demographic characteristics; (2) clinical, laboratory, and echocardiographic parameters; (3) procedural variables; and (4) clinical outcomes associated with the TAVI procedure. The clinical outcomes were assessed in accordance with the standardized endpoint definitions for TAVI of the Valve Academic Research Consortium.5,6 For stroke, all candidates for TAVI underwent an independent neurological examination prior to the procedure. Following the procedure, in every case of suspected neurologic symptoms, we involve a neurologist and/or geriatrician to evaluate the patient. Stroke event was determined according to the independent neurologist (with the appropriate imaging modality) and categorized according to the Valve Academic Research Consortium definition.
Short-term and long-term outcomes were evaluated, and included: all-cause and cardiovascular mortality; major adverse cardiac events (MACE, defined as a composite measure of death from any cause, acute myocardial infarction, and rehospitalization); and major adverse cardiac and cerebrovascular events (MACCE, defined as composite measure of death from any cause, acute myocardial infarction, rehospitalization, and stroke). Follow-up was performed during clinical visits or via telephone query.
This registry was approved by the ethics committee of the Rabin Medical Center.
Statistical methods. Continuous data are reported in terms of the mean (range), and differences between groups were tested with the unpaired Student’s t-test. Categorical data are presented as the number and percentage and differences between groups were tested using Fisher’s exact test. Survival curves and life tables were constructed according to the Kaplan-Meier method with log-rank analysis for significance. Multivariable logistic regression analysis was performed to evaluate the risk associated with extreme age for the endpoints of 1-year mortality and 1-year MACE. Prespecified covariates in the multivariable model included STS score and frailty for mortality and STS score, frailty, renal failure, and baseline valve area for MACE. These covariates were chosen based on groups’ differences. A P-value <.05 was considered statistically significant. All tests were two-tailed.
Results
The extremely aged group included 58 patients (21% of all patients) age ≥87 years (median, 89.0 years; range, 87-94 years; 67.2% women). All patients were at very high risk for surgical valve replacement. The mean logistic EuroSCORE I was 19.6 ± 11.2% and mean STS score was 9.4 ± 5.0% attributed mainly due to their age. The majority of these patients (72.5%) were functionally independent and did not require any assistance in activities of daily living. Only 6 patients (10.3%) were residents of protected housing. In comparison with the rest of the cohort (age 65-86 years), the extremely aged group had lower albumin and body mass index, and were less likely to have a history of percutaneous coronary intervention (Table 1). Furthermore, there was no significant difference in the overall risk assessment for surgery according to the logistic EuroSCORE; however, these patients were significantly more lean (P=.03) and frail (P=.01) (Table 1). The prevalence of frailty increased with age. For nonagenarians, excessive frailty was prevalent in 60% of the patients as opposed to octogenarians patients (20%) and patients <80 years (6%).
Aortic valve disease. All patients had severe symptomatic AS with a low functional capacity (New York Heart Association [NYHA] class III and IV). The maximal and mean gradients across the aortic valve were 83.3 ± 25.5 mm Hg and 54.0 ± 15.5 mm Hg, respectively. Mean valve area was 0.5 ± 0.2 cm2. Nine patients (22.5%) had decreased systolic left ventricular function (ejection fraction ≤45%). In comparison with the rest of the cohort, the extreme age patients were characterized by having more significant valvular disease with smaller valve orifice (P=.04), a higher frequency of patients was defined as having critical AS (P=.01) and lower ejection fraction (P<.001) (Table 1).
TAVI procedure. TAVI was performed via the transfemoral approach (82.5%) and under local anesthesia with sedation in most cases (70.7%) (Table 2). The valves used were CoreValve (74.1%) and Edwards Sapien (25.9%). There was no significant difference in variables associated with the TAVI procedure when compared with the rest of the cohort (Table 2). 
Clinical outcome. The procedural success rate in advanced age patients was 97.5%. One patient required an emergent open-heart surgery due to cardiac tamponade, which developed immediately after valve implantation. This was the only patient who died during hospitalization. The most common procedural and in-hospital complications were vascular complications and blood loss requiring blood transfusion and pacemaker implantation (Table 3). Most of the vascular complications were minor and were managed promptly using catheter techniques with no sequential disability. None of the patients suffered from cerebrovascular events. Pacemaker implantation was performed in 18.9% of patients due to atrioventricular conduction abnormalities that developed adjunct to the procedure. One patient developed a complete block that quickly progressed to asystole and required an emergent resuscitation, mechanical ventilation, and temporary pacemaker insertion. Ultimately, she regained full consciousness with no neurological or cognitive sequelae. She underwent permanent pacemaker insertion and was discharged.
In comparison with the rest of the cohort, periprocedural and in-hospital complication rates were similar (Table 3). The average hospital duration was 5.3 ± 3.7 days, which was similar to the rest of the cohort.
At 1-month follow-up, no additional patients had died, but 1 patient had suffered a major stroke (Table 3). The remaining 56 patients regained NYHA I-II functional capacity and improved their valve hemodynamics. The mean transaortic gradient decreased to an average of 8.7 ± 4.3 mm Hg. There was no significant difference in the overall mortality, MACE, or MACCE rates between the extreme age group and the rest of the cohort.
At 1-year follow-up, 3 patients (5.2%) had suffered from cerebrovascular events and 4 patients (6.9%) had died (Table 3). There was no significant difference in the overall mortality, MACE, or MACCE rates between the extreme age group and the rest of the cohort.
During a median follow-up period of 23 months (range, 1-53 months), 13 patients (22.4%) had died, mainly due to infectious and oncological diseases. In comparison with the rest of the cohort, there was no difference in the cumulative mortality rate during the maximal follow-up time (log rank, 0.87) (Figure 2).
Following a multivariate analysis, extreme age was not associated with increased 1-year mortality (odds ratio [OR], 0.63; 95% confidence interval [CI], 0.16-2.39; P=.49) or 1-year MACE (OR, 0.71; 95% CI, 0.26-1.92; P=.51) when compared with the rest of the cohort.
As for the overall well-being of the study population, at the latest follow-up (longest, 53 months), a total of 38/45 (84.4%) of the extremely aged patients were currently at good functional capacity (NYHA I or II) with no significant cognitive impairment. The median rehospitalization rate during the maximal follow-up time for any reason was 0.4 hospitalizations per patient per year, while 22/56 patients (39.3%) required no rehospitalization.
Discussion
We showed that in carefully selected patients at extreme age, the TAVI procedure is efficacious with reasonable overall risk, which is not significantly different from the less than extremely aged population. These patients were characterized by a higher frailty rate, but had a lower rate of significant co-morbidities. The overall risk assessment for surgical valve replacement was high, but not higher than the rest of the cohort, and was mainly attributed to their advanced age.
Currently, the TAVI procedure offers valve replacement therapy to patients with advanced age who were once considered unsuitable for surgery. Nevertheless, the prevalence of frailty increases incrementally with advancing age.10 Frail older adults are at high risk for major adverse health outcomes, including disability, falls, institutionalization, hospitalization, and mortality.11 Therefore, risk stratification of these patients is crucial for identifying appropriate candidates who may benefit from the TAVI procedure. The EuroSCORE7,8 and STS score9 are the most widely used risk scores to predict operative mortality in cardiac surgery. However, these models were developed and validated in a standard surgical risk population with low predictive power for patients approaching or even beyond 90 years of age. Variables such as functional capacity, frailty, and cognitive function are even more significant in the case of elderly patients who are candidates for TAVI for predicting morbidity and mortality following the procedure.12 In one study, frailty was found to be associated with increased mortality following TAVI, but not with increased periprocedural complications.13
With the lack of comprehensive models, risk assessment of very elderly patients before TAVI becomes a challenge. Therefore, the Valve Academic Research Consortium 2included these variables with a recommendation for their evaluation.6 In our study, frailty and variables such as low body mass index and low albumin were prevalent. As expected, we showed a leap in the frequency of frail patients especially above the age of 90 years as compared with younger patients.
Most data regarding the outcomes of elderly patients derive from studies that included high-risk surgical patients;14,15 however, these studies were not dedicated to patients with extreme age. Currently, the experience with octogenarian and nonagenarian patients is growing, as they are frequently referred for TAVI. Some reports regarding the complication rate and outcomes of patients with extreme age are reassuring, but are insufficient.16-19 Moreover, recently, Martínez-Sellés et al20 compared three therapeutic approaches in octogenarian patients: surgical valve replacement, TAVI, and conservative managements, and showed that intervention with either surgery or TAVI was associated with a better prognosis.
Although we do not have a current registry of all patients who were screened for TAVI at our center, according to our previous report,21 it is estimated that one-third of all screened patients in the years 2008-2011 were referred to TAVI by our heart team. Extreme age patients were mostly referred to balloon valvuloplasty and conservative medical therapy. Since then, due to changes in guidelines and increasing experience, this ratio may have changed considerably. According to the profile of our extreme age cohort, it is apparent that these patients were meticulously selected by our heart team as suitable candidates. We have therefore shown that with careful selection, a good overall long-term survival and well-being can be achieved in extreme age patients. We would recommend further evaluation of our results in larger trials in order to establish robust recommendations for better selection of patients with extreme age who may benefit from TAVI.
Study limitations. Our study is a retrospective single-center study with its inherent limitations and a relatively small cohort analyzed that may not reveal the true event rate. The study event rate, especially in the case of stroke, was relatively lower than previously reported. Since stroke diagnosis was performed based on clinical suspicion and by routine assessment following the procedure, this potentially could lead to underreporting of the true stroke rate. Nevertheless, stroke rate has been recently reported lower in large registries.22
Data regarding patients with extreme age who were rejected by the heart team for TAVI are lacking and would have been useful to better characterize selection criteria. Furthermore, we did not perform a routine cognitive or quality of life assessment, which would have contributed to the outcome evaluation.
Conclusion
In our experience, patients at extreme age, who are meticulously selected by the heart team, benefit from TAVI with reasonable overall risk of periprocedural complications, good overall survival, and functional class. Collaboration between cardiologists and geriatricians will likely become a standard approach to enhance the assessment of these frail patients and identify those most likely to benefit from TAVI.
References
1. Lindroos M, Kupari M, Heikkila J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol 1993;21:1220-1225.
2. Vahanian A, Alfieri O, Andreotti F, et al; Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012;33:2451-2496.
3. Nishimura RA, Otto CM, Bonow RO, et al. 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.
4. Vahanian A, Otto CM. Risk stratification of patients with aortic stenosis. Eur Heart J. 2010;31:416-423.
5. Leon MB, Piazza N, Nikolsky E, et al. Standardized endpoint definitions for transcatheter aortic valve implantation clinical trials: a consensus report from the Valve Academic Research Consortium. Eur Heart J. 2011;32:205-217.
6. Kappetein AP, Head SJ, Généreux P, et al. Updated standardized endpoint definitions for transcatheter aortic valve implantation: the Valve Academic Research Consortium-2 consensus document. J Am Coll Cardiol. 2012;60:1438-1454.
7. Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European System for Cardiac Operative Risk Evaluation (EuroSCORE). Eur J Cardiothorac Surg. 1999;16:9-13.
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.
9. O’Brien SM, Shahian DM, Filardo G, et al; Society of Thoracic Surgeons Quality Measurement Task Force. The Society of Thoracic Surgeons 2008 cardiac surgery risk models, part 2: isolated valve surgery. Ann Thorac Surg. 2009;88:S23-S42.
10. Fried LP, Tangen CM, Walston J, et al; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–M156.
11. Makary MA, Segev DL, Pronovost PJ, et al. Frailty as a predictor of surgical outcomes in older patients. J Am Coll Surg. 2010;210:901-908.
12. Afilalo J, Mottillo S, Eisenberg MJ, et al. Addition of frailty and disability to cardiac surgery risk scores identifies elderly patients at high risk of mortality or major morbidity. Circ Cardiovasc Qual Outcomes. 2012;5:222-228.
13. Green P, Woglom AE, Genereux P, et al. 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.
14. Kodali SK, Williams MR, Smith CR, et al; PARTNER Trial Investigators. Two-year outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med. 2012;366:1686-1695.
15. Makkar RR, Fontana GP, Jilaihawi H, et al; PARTNER Trial Investigators. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med. 2012;366:1696-1704.
16. De Feo M, Vicchio M, Della Corte A, et al. Lack of definite indication criteria for choosing between transcatheter implantation and surgical replacement of the aortic valve. J Cardiovasc Med (Hagerstown). 2013;14:158-163.
17. Havakuk O, Finkelstein A, Steinvil A, et al. Comparison of outcomes in patients ≤85 versus >85 years of age undergoing transcatheter aortic-valve implantation. Am J Cardiol. 2014;113:138-141.
18. Noble S, Frangos E, Samaras N, et al. Transcatheter aortic valve implantation in nonagenarians: effective and safe. Eur J Intern Med. 2013;24:750-755.
19. Akin I, Kische S, Paranskaya L, et al. Morbidity and mortality of nonagenarians undergoing CoreValve implantation. BMC Cardiovasc Disord. 2012;12:80.
20. Martínez-Sellés M, Gómez Doblas JJ, Carro Hevia A, et al; the PEGASO Registry Group. Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention. J Intern Med. 2014;275:608-620.
21. Dvir D, Sagie A, Porat E, et al. Clinical profile and outcome of patients with severe aortic stenosis at high surgical risk: single-center prospective evaluation according to treatment assignment. Catheter Cardiovasc Interv. 2013;81:871-881.
22. Mack MJ, Brennan JM, Brindis R, et al; STS/ACC TVT Registry. Outcomes following transcatheter aortic valve replacement in the United States. JAMA. 2013;310:2069-2077.
______________________________________________
From the Cardiology Department, Rabin Medical Center, Petah-Tikva affiliated to the “Sackler” Faculty of Medicine, Tel-Aviv University, Israel.
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 December 22 2014, provisional acceptance given March 5, 2015, final version accepted May 11, 2015.
Address for correspondence: Katia Orvin, MD, Cardiology Department, Rabin Medical Center, 39 Jabotinsky St. 49100, Petach Tikva, Israel. Email: katiaorvin@gmail.com
