Transcatheter Aortic Valve Implantation in Patients of Extreme Age: Age is Just a Number

In 1968, several years after the first surgical aortic valve replacement (SAVR), Morrow and Braunwald described aortic stenosis (AS) as affecting patients 40-60 years old, with a bicuspid aortic valve or rheumatic heart disease.¹ Times have changed. Today, AS is predominantly a degenerative fibrocalcific disease affecting the elderly. Based on a pooled analysis of multiple recent databases, the prevalence of severe AS in patients >75 years is 3.4%,² with the number of patients >75 years expected to double by the year 2050. AS is a disease of aging, and based on Monte Carlo simulations, 290,000 patients above age 75 are transcatheter aortic valve implantation (TAVI) candidates, with nearly 27,000 becoming eligible for TAVI annually.² Any approach to treating this patient population will need to be focused on the safe and effective application of surgical and non-surgical approaches in elderly patients. 

SAVR has been the gold-standard treatment for severe AS for over 50 years. In a recent study of over 141,000 patients in the Society of Thoracic Surgeons (STS) database undergoing SAVR, the overall mortality is a very favorable 2.5%, but there remains limited outcome data in octogenarians and nonagenarians, as these patients are often deemed too high risk to undergo the procedure.³ Very few studies have been published to date with SAVR outcomes in this patient population.^4,5 With the development of TAVI as an alternative treatment strategy in inoperable or high-risk patients with severe AS, there have been over 100,000 such procedures since the first was performed by Alain Cribier in 2002.⁶ Many AS patients of extreme age are now treated with TAVI in lieu of SAVR, as evidenced by the fact that the median age of patients undergoing TAVI in the United States is 84 years,⁷ significantly higher than the median age of 70 years for SAVR.³ 

Is there an age at which patients should be considered too high risk for TAVI?  Although the pivotal TAVI studies, including the PARTNER and CoreValve trials, have enrolled octogenarians (mean age for TAVI: 83.1 years for PARTNER B, 83.6 years for PARTNER A, and 83.1 years for US CoreValve High-Risk Study),^8-10 there are limited published studies or subgroup analyses focusing on patients of extreme age. In the current issue of the Journal of Invasive Cardiology, Orvin et al compare the outcomes of TAVI in 58 extreme-age patients (age ≥87 years; mean age, 89.0 years) with a mean STS score of 9.4% to 218 less elderly patients with a significantly lower mean STS score of 7.7% (mean age, 80.8 years).¹¹ This important analysis demonstrates that the application of this ground-breaking technology in patients of extreme age can be applied safely and effectively, with outcomes quite similar to the typical “young” elderly TAVI patient with a lower STS score. Orvin et al found excellent short-term and long-term outcomes. There was no significant difference in any outcome compared with the less elderly cohort. 

It is clear from this report that age alone should not be the defining parameter in limiting access to this technology. Extreme age will co-localize with other risks for adverse outcomes, including renal disease, LV dysfunction, pulmonary disease, and neurologic and cognitive deficits; however, it is not an independent predictor of poor outcomes. Instead, with a great deal of foresight, the field of TAVI has developed an early recognition that assessing individual patient risk is more important than age in determining the risk-benefit ratio for TAVI. However, the tools available for assessing this risk have expectedly lagged behind the clinical need. The STS predicted risk of mortality (PROM) score and EuroSCORE are tools used by surgeons to assess operative risk.^12,13 While the majority of patients undergoing SAVR have an STS score <5%,¹⁴ TAVI trials and subsequent approvals have focused on patients at high risk or deemed inoperable. The risk of TAVI has been definitively demonstrated to correlate with STS risk score, with inoperable patients having a greater risk of death (30.7% mortality at 1 year in PARTNER B) than patients at high surgical risk (24.2%  mortality at 1 year in PARTNER A).^9,10  

Unfortunately, the conventional risk models, the STS score and EuroSCORE, are in essence borrowed tools, and are insufficient for discriminating TAVI risk. For example, the incorporation of frailty and disability into risk prediction for TAVI in this population appears to improve the ability to predict poor outcomes, as evidenced by the fact that the frailty index (based on assessment of cognition, mobility, nutrition, instrumental and basic activities of daily living) was found to be predictive of functional decline and mortality after TAVI,^15,16 and a recent report describes the addition of frailty and disability as providing incremental value to the STS score for coronary artery bypass graft and/or valve surgery in a multicenter cohort of elderly patients.¹⁷ Recently, two specific TAVI risk models have been developed – the OBSERVANT risk score and the PARTNER risk score – which in preliminary evaluations improve upon the conventional STS/EuroSCORE  risk models.^18,19 With over 100,000 cases performed to date, it is time to further develop and confirm these and other specific TAVI scoring systems, based on TAVI, not SAVR outcomes, to better predict short-term and intermediate-term results from this emerging procedure and to allow better patient screening, regardless of age.

References

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17. 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.
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19. Capodanno D, Barbanti M, Tamburino C, et al. A simple risk tool (the OBSERVANT score) for prediction of 30-day mortality after transcatheter aortic valve replacement. Am J Cardiol. 2014;113:1851-1858.

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From the Division of Cardiology, Loyola University Medical Center, Maywood, Illinois.

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.

Address for correspondence: John J. Lopez, MD, Division of Cardiology, Loyola University Medical Center, Stritch School of Medicine, 2160 S. First Avenue, Maywood IL 60153. Email: JLOPEZ7@lumc.edu