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- S0735109716348963-6dc79eaefb1a78b9a6c156f0246dd16aJohn D. Carroll, MD∗ ()
- Department of Medicine, Division of Cardiology, University of Colorado School of Medicine, Aurora, Colorado
- ↵∗Reprint requests and correspondence:
Dr. John D. Carroll, University of Colorado Anschutz Medical Campus, Mail Stop B132, Leprino Office Building, Room 524, 12401 East 17th Avenue, Aurora, Colorado 80045.
The early results of the French national transcatheter aortic valve implantation registry, FRANCE 2 (FRench Aortic National CoreValve and Edwards registry), were reported previously (1). The initial report of FRANCE 2 identified the need for safer and more effective technology to reduce the need for alternative access and the high rates of paravalvular leakage. The current publication in this issue of the Journal includes longer-term outcomes of 4,201 patients treated at all sites in France from January 2010 to January 2012 (2). The registry has multiple positive attributes including use of a clinical events committee to adjudicate the cause of mortality.
The First Tsunami of TAVR
The first tsunami of transcatheter aortic valve replacement (TAVR) began with the introduction of this transformative treatment for patients who had no treatment options or only high-risk surgical AVR, as reported in FRANCE-2. This first tsunami is still rising as additional lower risk patients are being treated with TAVR. Before considering the second tsunami, we should consider what we have learned.
FRANCE 2 provides 3-year mortality results that are sobering. Specifically, total mortality was 42%, and after adjudication, it was found that cardiovascular mortality occurred at a rate of 19.3%. The authors concluded that late mortality was primarily due to noncardiac causes. In comparison, PARTNER (The Placement of Aortic Transcatheter Valves) Cohort B (inoperable) patients randomized to medical management had a 3-year total mortality of 80.9% with a cardiovascular mortality of 74.5% (3). Those patients randomized to TAVR had an average 3-year mortality of 54.1%, with a cardiovascular mortality of 41.4%. PARTNER Cohort A (high-risk) patients randomized to TAVR had a 5-year mortality of 67.8% with a cardiovascular mortality of 53.1% (4). All studies cited used a clinical events committee to adjudicate cause of mortality. While it is unclear why FRANCE 2 had a lower cardiovascular morality, there is broad agreement that even after successful TAVR, the majority of patients will have died by 5 years.
Recent U.S. census and Medicare data show the average life expectancy for a 50-year-old patient is 31.5 years, 14.9 years for a 70-year-old patient, 8.7 years for an 80-year-old patient, and 4.6 years for a 90-year-old patient (5). Therefore, a treatment’s mortality benefit is highly dependent on the age of the patient being treated. The absolute number of years of survival gained by TAVR is thus limited when applied to an elderly population.
The FRANCE 2 investigators assessed the determinants of survival after TAVR. Multivariate predictive factors of 3-year all-cause mortality rate included male sex, low body mass index, atrial fibrillation, dialysis, New York Heart Association functional class III or IV, higher logistic EuroSCORE, transapical and subclavian approaches, need for permanent pacemaker implant, and post-implantation periprosthetic aortic regurgitation (AR) grade ≥2/4. As with other predictive models of mortality after TAVR, we see the major impact of comorbid conditions, both cardiac and noncardiac, on post-TAVR survival. Procedure-related factors with effects on survival have started to decline as TAVR technology improves and the learning curve is ascended. While the burden of comorbid conditions from minimal to substantial has an impact on survival, the absolute differences in survival are relatively small because of the inherently short life expectancy of people in their eighth decade of life.
Survival benefits from TAVR are important; however, improved or maintained functional status, quality of life, and freedom from hospitalization are other benefits that become extremely important for judging the value of TAVR. FRANCE 2 revealed that, after TAVR hospital readmission for any reason occurred in 1,032 patients (28.1%) between 30 days and 1 year, 557 patients (21.5%) during the second year, and 515 patients (25.6%) during the third year. Of those who survived for 3 years post TAVR, 90.0% were asymptomatic or only mildly symptomatic.
The Second Tsunami of TAVR
The second tsunami will be a huge wave formed by the demographic surge in the elderly population, who will have a high prevalence of degenerative aortic stenosis. The magnitude of this wave and the multifaceted implications need to be understood.
In France, the proportion of the population ≥75 years of age was 6.3% in 1996 and has risen to 9.1% in 2016, with an absolute increase from 3,752,000 to 6,081,000 individuals (6). In the United States, the elderly population will reach 50 million by 2019, and 1 in 5 U.S. citizens will be elderly by 2030, with 8.5 million reaching the oldest of the old (i.e., >85 years old) (7).
This “elderly boom” has started due to increased longevity but will dramatically increase as the leading edge of the “'baby boomers” reaches this age group. The major demographic phenomenon of the post-WW II period was the substantial rise in birth rates (i.e., the “baby boom”). The population pyramids of United States and France, as well as many other countries, have a disproportionate percentage of the population clustered in the age group born between 1946 and 1964 (7).
The prevalence of aortic stenosis and its strong relationship to aging has recently been reviewed. The dominant cause of aortic stenosis in the 21st century is degenerative. Over the age of 75 years, degenerative aortic stenosis is present in 12.4% of individuals and is hemodynamically severe in 3.4% (8). Bicuspid aortic valves occurring in 1% to 2% of the population will likely be the dominant cause of aortic stenosis in younger age groups.
The Future of TAVR
A major reduction in the average age of patients being treated with TAVR is not likely to occur even if lower-risk patients are treated. The majority of aortic stenosis patients will continue to be elderly based on the dominant degenerative causes of aortic stenosis and its transition to a symptomatic and hemodynamically severe state after the age of 75, and often after the age of 80.
A substantial increase in the volume of TAVR patients is likely to parallel the increase in the elderly population, especially with the arrival of the baby boomers after 2020. In 2015, approximately 25,000 TAVR procedures using U.S. Food and Drug Association-approved devices were performed in the United States. In 2020, it is conceivable that 100,000 TAVR procedures a year will be reached.
The heterogeneity of TAVR benefit is increasingly clear especially in the elderly with comorbid conditions and warrants further definition of our ability to predict those who are highly unlikely to benefit. While the risks and burden of TAVR will continue to decline, driven by experience and technology, many patients will continue to have the comorbidities and frailty associated with aging, and these patients will define the limits of benefits from TAVR.
The costs associated with TAVR combined with the major increase in the number of patients who are eligible will present enormous challenges to health care budgets around the world. High costs of devices will need to be reduced perhaps by competition, lower production costs associated with higher volume, and reduction in costs associated with regulatory approval. Furthermore new delivery and device technologies that further reduce complications, including the frequent need for permanent pacemakers, must be combined with efficient care processes that reduce hospital costs.
Therapies to prevent or slow degenerative aortic stenosis should be sought despite the initial failures of statin trials. However, the aortic valve is another body part that has a finite lifespan after opening and closing approximately 3 billion times by the age of 80. TAVR has joined hip replacement, cataract surgery, and hearing aid implantation in the armamentarium of replacement technologies directed at prolonging life and maintaining the reasonable functional status of mature adults (9).
In conclusion, TAVR is not the fountain of youth but is for most a reprieve from rapid functional decline, misery, and death due to progressive aortic stenosis. When successfully performed without major complications, it returns the patient to a prognosis and a day-to-day existence defined by their age, sex, other diseases, frailty, socioeconomic status, and patient reported health status.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Carroll is a site investigator for PARTNER 2 (Edwards LifeSciences), SALUS (Direct Flow), and Low Risk TAVR vs. SAVR (Medtronic); and a member of the Society of Thoracic Surgeons and American College of Cardiology Transcatheter Valve Registry steering committee.
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- ↵National Institute on Aging. Aging in the United States: Past, Present, and Future. U.S. Department of Commerce, Bureau of the Census. Washington, DC. Available at: https://www.census.gov/population/international/files/97agewc.pdf. Accessed July 31, 2016.
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