At 3 Years Post-TAVR, Valve Performance Holds Steady and Most Mortality Is Noncardiac: FRANCE 2 Registry
A comprehensive look at long-term TAVR outcomes in the FRANCE 2 registry shows that at 3 years the valves continue to be effective. All-cause mortality—mainly predicted by baseline patient factors like A-fib and male sex but also by procedural and periprocedural variables—is more common over this lengthier horizon than cardiac mortality, researchers confirmed.
Details of their findings were first released at EuroPCR 2016 and are being published in the October 11, 2016, issue of the Journal of the American College of Cardiology.
Lead author Martine Gilard, MD, PhD (Brest University Hospital, France), told TCTMD the main message of the study is two-fold. “The sustained clinical improvement and low rate of clinical events after the first month contribute to strengthening the current indication for TAVR in high-risk patients,” she noted in an email, adding, “The absence of deterioration of valve function is also relevant with regard to the perspective of potentially extending the indications to patients at lower risk. In FRANCE 2, the number of patients with echocardiographic follow-up is very sizeable (1,000 patients at 3 years).”
The fact that no patients needed repeat treatment for valve failure during the 3-year time frame appeared to be less meaningful to Farrel Hellig, MD (Sunninghill Hospital, Johannesburg, South Africa), who commented on the study for TCTMD. Asked whether this was reassuring, in light of concerns about valve degeneration aired earlier this year, he replied: “I think 3 years is too soon to expect any noticeable degeneration.”
While overall the FRANCE 2 analysis reveals no big surprises, Hellig said, the link between A-fib and survival is “interesting.”
Atrial fibrillation and aortic stenosis (AS) “make poor bedfellows,” he observed to TCTMD via email. “The onset of [A-fib] is often the cause of sudden deterioration in aortic stenosis patients and can be devastating and increase procedural risk substantially.” NYHA class III/IV, also a predictor of higher 3-year mortality in the FRANCE 2 registry, “may reflect the development of LV dysfunction or worsening LV function, increasing procedural risk,” Hellig added.
In their paper, Gilard and colleagues make the case that the “strong predictive value” of both these factors “reflects the evolutionary stage of AS and shows that late referral for TAVR impairs late survival, even in high-risk patients.”
Hellig, taking this one step further, said, “Asymptomatic severe AS should be treated earlier than watchful waiting in my view.”
A Mix of Patient and Procedural Factors
For their FRANCE 2 analysis, Gilard et al assessed outcomes through a median of 3.8 years in 4,201 symptomatic TAVR patients, all contraindicated or at high risk for surgery, treated between January 2010 and January 2012 at 34 centers in France and Monaco. Most cases involved the transfemoral approach (73%) followed by transapical (18%), subclavian (6%), and transaortic or transcarotid (6.8%).
Vital status was available for 97.2% of patients at 3 years, when the rates of all-cause and cardiac mortality were 42.0% and 17.5%, respectively.
Multivariate predictors of 3-year risk of all-cause mortality were primarily patient factors: male sex, low body mass index, A-fib, dialysis, NYHA functional class III or IV, and logistic EuroSCORE >30. Use of the transapical or subclavian approach each were associated with higher risk, as was need for permanent pacemaker implantation within 30 days and post-TAVR periprosthetic aortic regurgitation grade of 2-4.
However, Valve Academic Research Consortium-defined severe events were mostly restricted to the first month after implantation and thereafter occurred in fewer than 2% of patients per year. “Mean gradient, valve area, and residual aortic regurgitation were stable during follow-up,” the authors note, reporting that by 3 years no patients had structural valve failure requiring reoperation or reintervention.
TAVR Not the ‘Fountain of Youth,’ but Age Is No Barrier
Notably, age was not among the various predictors of all-cause mortality, the researchers say. “The fact that age was not associated with survival in this large cohort supports the attitude of not refusing surgery for aortic stenosis on the sole grounds of age.”
But in an accompanying editorial, John D. Carroll, MD (University of Colorado School of Medicine, Aurora), calls the total mortality and CV mortality rates “sobering,” despite their being substantially lower than rates observed in the PARTNER trial, which like the FRANCE 2 registry used a clinical events committee to adjudicate cause of death. “While it is unclear why FRANCE 2 had a lower cardiovascular mortality, there is broad agreement that even after successful TAVR, the majority of patients will have died by 5 years,” he notes.
Carroll cites US census and Medicare data showing that average life expectancy shortens as patients age: from 31.5 years remaining in a 50-year-old to 14.9 years in a 70-year-old, 8.7 years in an 80-year old, and 4.6 years in a 90-year-old.
“Therefore a treatment’s mortality benefit is highly dependent on the age of the patient being treated,” he stresses. “The absolute number of years of survival gained by TAVR is thus limited when applied to an elderly population.”
Asked how to balance this shorter lifespan with the fact that older age itself did not impair survival in FRANCE 2, Gilard replied: “After the first year postimplantation of the TAVI [device], the evolution of the patients seems similar to the general population.”
Acknowledging that life expectancy can be inherently limited for some elderly patients, Hellig still agreed that age alone should not preclude TAVR. “Age is not really a strong clinical marker in itself,” he noted, placing the blame instead on the comorbidities that tend to be more common in the elderly. “A pragmatic approach,” Hellig suggested, “is to risk stratify a patient and not use a specific age as an exclusion for therapy.”
Even if TAVR’s influence on survival may be less consequential for the oldest patients, it still holds benefits in terms of functional status, quality of life, and freedom from hospitalization, Carroll notes.
“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,” he concludes. “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.”
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Gilard G, Eltchaninoff H, Donzeau-Gouge P, et al. Late outcomes of transcatheter aortic valve replacement in high-risk patients: the FRANCE-2 Registry. J Am Coll Cardiol. 2016;68:1637-1647.
Carroll JD. TAVR prognosis, aging, and the second TAVR tsunami: insights from France. J Am Coll Cardiol. 2016;68:1648-1650.
- Gilard reports no relevant conflicts of interest.
- Hellig reports serving as a proctor for Edwards Lifesciences.
- Carroll reports being 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.