CGA-TAVI Registy

Senile, calcific aortic stenosis (AS) is the most common valvular abnormality
in Europe. At 75 years of age 4.6% of the population have severe AS and by 85
years old this has risen to 8%. With an increasingly elderly population, this
presents a major healthcare burden. Once symptoms develop, the one-year and
five-year survival rates of unoperated patients are dramatically curtailed at
32% and 60%, respectively. Symptomatic, severe AS is therefore a class I
indication for a surgical aortic valve replacement (sAVR) and the efficacy of
aortic valve replacement (AVR) for symptomatic AS is well established

Despite this, a large proportion of this cohort remain untreated because of
advanced age and multiple comorbidities * some estimates suggest that 30*40%
of elderly patients that would meet the criteria for surgery are never offered
it. It is in these patients that transcatheter aortic valve implantation (TAVI)
has seen its most marked growth since it was first demonstrated by Cribier et
al. using a transvenous, transseptal approach. There have been encouraging
results in the short and longer term registries and recently a randomized
controlled trial demonstrated an absolute reduction of 20% in all-cause
mortality compared with medical therapy in patients unsuitable for surgery.
There are currently several devices commercially available from Edwards,
Medtronic, St. Jude, Symetis and JenaValve

Comprehensive geriatric assessment (CGA) is a multidimensional and
interdisciplinary diagnostic process to determine the medical, psychological,
and functional capabilities of an elderly person in order to develop a
coordinated and integrated plan for treatment and follow-up. CGA usually
includes clinical, cognitive, functional, nutritional, and social parameters
and is carried out using six standardized scales and information on medications
and social support network, for a total of 63 items in eight domains. A
Multidimensional Prognostic Index (MPI) aggregates the total scores of the
eight domains of the CGA, expressing it as a score from 0 to 1. Three grades of
MPI are defined: low risk 0.0-0.33; moderate risk 0.34-0.66; and severe risk
0.67-1.0. Higher MPI scores are significantly associated with older age, female
sex, lower educational level, and higher mortality. The discrimination of the
MPI is good, with a ROC area of 0.751 (95%CI 0.70-0.80) at 6 months and 0.751
(95%CI 0.71-0.80) at 1 year of follow-up. Taken together the MPI is a CGA that
can be routinely carried out in elderly patients in a geriatric acute ward to
predict 1-year mortality.

Frailty is a geriatric syndrome that is characterized by increased
vulnerability to stressors because of diminishing physiological function.
Stressors may include illness or surgery, and frailty is associated with an
increased risk of co-morbidities and mortality. Currently, measures of physical
disability, in particular five-meter gait speed, are emerging as the most
accurate parameters for assessing frailty. This is because there is a strong
association between gait speed, which can be objectively measured, and
dependence on outside help in activities of daily living. Moreover, it was
shown that while frailty was not related with increased periprocedural
complications, it was associated with a longer post-TAVI hospital stay and with
increased 1-year mortality . Thus, it has been suggested that multidimensional
risk prediction (involving cognition, nutrition, mobility, activities of daily
living, and frailty index) could be useful for establishing global risk scores
in this population. Ultimately, the incorporation of these measures into
clinical decision-making related to TAVI candidates is essential for providing
the best possible care to this vulnerable group of patients. However, so far,
there remains a lack of consensus on the definition of frailty, and
decision-making can be difficult because frailty is not included in either the
STS or the EuroSCORE scores for calculating surgical risk.
There are two recent publications on the value of a Multidimensional Geriatric
Assessment (MGA) as predictor of mortality and major adverse cardiovascular and
cerebral events (MACCE) after transcatheter aortic valve implantation (TAVI).
Stortecky et al. assessed the impact of an MGA on mortality and MACCE rates in
100 consecutive patients of at least 70 years undergoing TAVI. Global risk
scores (Society of Thoracic Surgeons [STS] score, EuroSCORE) and MGA-based
scores (cognition, nutrition, mobility, activities of daily living [ADL], and
frailty index) were evaluated as predictors of all-cause mortality and MACCE 30
days and 1 year after TAVI in regression models. Bivariable analyses, including
STS score or EuroSCORE suggested independent associations of MGA-based scores
(e.g., OR of frailty index: 3.29, 95% CI: 1.06 to 10.15, for 1-year mortality
in a model including EuroSCORE). Because the patient number was too low to
allow multivariable adjusted prediction, they concluded that larger
investigations are needed for the development and validation of improved risk
prediction models. Schoenenberger et al. [
25] aimed to assess predictors of functional decline in the elderly. Functional
decline was observed in 22 (20.8%) of 106 surviving patients. EuroSCORE (OR per
10% increase 1.18, 95% CI: 0.83-1.68, P = 0.35) and STS score (OR per 5%
increase 1.64, 95% CI: 0.87-3.09, P = 0.13) weakly predicted functional
decline. In contrast, the frailty index strongly predicted functional decline
in univariable (OR per 1 point increase 1.57, 95% CI: 1.20-2.05, P = 0.001) and
bivariable analyses (OR: 1.56, 95% CI: 1.20-2.04, P = 0.001 controlled for
EuroSCORE; OR: 1.53, 95% CI: 1.17-2.02, P = 0.002 controlled for STS score).
Overall predictive performance was best for the frailty index [Nagelkerke's
R(2) (NR(2)) 0.135] and low for the EuroSCORE (NR(2) 0.015) and STS score
(NR(2) 0.034). They concluded that the frailty index, but not established risk
scores, was predictive of functional decline. Refinement of this index might
help to identify patients who potentially benefit from additional geriatric
interventions after TAVI.

The purpose of this registry is to expand upon existing data sets, to identify
patient characteristics and indicators related to complications and clinical
benefits for patients with symptomatic severe calcific degenerative aortic
stenosis that are undergoing treatment with the commercially available Edwards
SAPIEN XT Transcatheter Heart Valve.

This is an international, multi-center, prospective, observational registry in
20 sites across Europe with consecutive patient enrollment. A total of 200
patients across Europe are to be enrolled in the registry during the enrollment
period by contributing sites.

Execution of the CGA involves negligible risks, and the burden involves
approximately five hours time-investment: three to four-hour visit to the
outpatient clinic of the AMC inclusing comprehensive medical history,
questionnaires and short physical examination, spread over three months. The
rest of the time consists of answering telephone questions (to partner or
family members, if necessary) about mortality and hospitalization at 12 months
after surgery.