Journal of the American College of Cardiology Vol. 63, No.

8, 2014
Ó 2014 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00
Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2013.09.070

JACC WHITE PAPER

Frailty Assessment in the

Cardiovascular Care of Older Adults
Jonathan Afilalo, MD, MSC,* Karen P. Alexander, MD,y Michael J. Mack, MD,z
Mathew S. Maurer, MD,x Philip Green, MD,x Larry A. Allen, MD, MPH,k
Jeffrey J. Popma, MD,{ Luigi Ferrucci, MD, PHD,# Daniel E. Forman, MD**
Montreal, Quebec, Canada; Durham, North Carolina; Plano, Texas; New York, New York;
Aurora, Colorado; Boston, Massachusetts; and Baltimore, Maryland

Due to the aging and increasingly complex nature of our patients, frailty has
become a high-priority theme in cardiovascular medicine. Despite the recognition of
frailty as a pivotal element in the evaluation of older adults with cardiovascular
disease (CVD), there has yet to be a road map to facilitate its adoption in routine
clinical practice. Thus, we sought to synthesize the existing body of evidence and
offer a perspective on how to integrate frailty into clinical practice. Frailty is a
biological syndrome that reflects a state of decreased physiological reserve and
vulnerability to stressors. Upward of 20 frailty assessment tools have been developed,
with most tools revolving around the core phenotypic domains of frailtydslow
walking speed, weakness, inactivity, exhaustion, and shrinkingdas measured by
physical performance tests and questionnaires. The prevalence of frailty ranges from
10% to 60%, depending on the CVD burden, as well as the tool and cutoff chosen to
define frailty. Epidemiological studies have consistently demonstrated that frailty
carries a relative risk of >2 for mortality and morbidity across a spectrum of stable
CVD, acute coronary syndromes, heart failure, and surgical and transcatheter
interventions. Frailty contributes valuable prognostic insights incremental to existing
risk models and assists clinicians in defining optimal care pathways for their patients.
Interventions designed to improve outcomes in frail elders with CVD such as
multidisciplinary cardiac rehabilitation are being actively tested. Ultimately, frailty
should not be viewed as a reason to withhold care but rather as a means of delivering
it in a more patient-centered fashion.

From the *Divisions of Cardiology and Clinical Epidemiology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; yDivision of Cardiology,
Duke University Medical Center, Durham, North Carolina; zDivision of Cardiothoracic Surgery, Baylor Health Care System, The Heart Hospital Baylor Plano,
Plano, Texas; xDivision of Cardiology, Columbia University Medical Center, New York, New York; kDivision of Cardiology, University of Colorado School of
Medicine, Aurora, Colorado; {Division of Cardiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; #National Institute on Aging, National
Institutes of Health, Baltimore, Maryland; and the **Division of Cardiovascular Medicine, Brigham and Women’s Hospital, VA Boston Healthcare Center,
Boston, Massachusetts. Dr. Popma has received research grants from Medtronic, Boston Scientific, and Abbott; and has served on advisory boards for Boston
Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Manuscript received September 25, 2013; accepted September 30, 2013.
748 Afilalo et al. JACC Vol. 63, No. 8, 2014
Frailty in Cardiovascular Care March 4, 2014:747–62

Abbreviations Frailty, from the French frêle Assessment of frailty is instrumental to refine estimates of
and Acronyms meaning of little resistance, is a risk and guide patients toward personalized treatment plans
ADL = activities of daily
biological syndrome that reflects that will maximize their likelihood of a positive outcome.
living a state of decreased physiologi- For example, given 2 heart failure patients with similar
AS = aortic stenosis cal reserve and vulnerability to chronological age and comorbidities, the presence of
AVR = aortic valve stressors (1). Stressors are broadly objectively-measured frailty alerts the clinician that 1 of the
replacement classified as acute or chronic ill- 2 patients has a substantially higher risk of mortality and
CAD = coronary artery ness (e.g., myocardial infarction) major morbidity. Furthermore, the frail patient faces a
disease
or iatrogenic (e.g., cardiac surgery). higher risk from invasive procedures but also a potential
CVD = cardiovascular
When exposed to such stressors, benefit from interventions such as cardiac rehabilitation to
disease
frail patients are at risk for counteract the physical weakness characteristic of frailty.
SPPB = Short Physical
Performance Battery marked and often dispropor- A critical mass of clinicians, researchers, and policy makers
TAVR = transcatheter aortic tionate decompensation, adverse have embraced the concept of frailty, yet the lack of a sci-
valve replacement events, procedural complications, entific road map to integrate frailty into practice has been a
prolonged recovery, functional de- limiting factor.
cline, disability, and mortality (2). The objectives of this state-of-the-art paper are to:
Frailty has become a high-priority theme in cardiovascular 1) summarize the existing body of evidence for frailty in
medicine due to the aging and increasingly complex nature patients with cardiovascular disease (CVD); 2) offer a
of our patients (3). Evolving technical innovations have enabled perspective on integrating frailty into current clinical practice;
clinicians to treat a wider array of patients with devices and and 3) point out the knowledge gaps for future research.
procedures, many of whom were previously regarded as “ineli-
gible” (4,5). Uncertainty regarding individual benefit from such
treatments has been coupled with growing economic constraints
Pathobiology of Frailty
on healthcare systems, such that the issue of appropriate patient Frailty biology is a field of ongoing research and debate (6).
selection has intensified. There is an unmet need to optimize Putative mechanisms revolve around dysregulation of the
resource allocation to prevent patients from receiving costly but immune, hormonal, and endocrine systems (7)dnotably,
futile interventions. up-regulation of inflammatory cytokines (8–10), decreased

Figure 1

Two of the Pathways Leading Toward the Phenotype of Frailty

(Left) The age-associated activation of inflammatory cells and decline in androgen hormones upset the balance between catabolic and anabolic stimuli, respectively, leading to
a decline in muscle mass and composition known as sarcopenia. This detrimental response is aggravated in patients with insulin resistance and metabolic syndrome. Addition
of bed rest and malnutrition initiates a vicious cycle of further decline in muscle mass, limiting the necessary mobilization of amino acids in times of stress. (Right)
The accumulation of subclinical impairments in multiple organ systems resulting from cardiovascular disease, lifelong “wear and tear,” and/or genetic predispositions lead
to decreased homeostatic reserve and resiliency to stressors. Other pathophysiological pathways have been proposed. Biological pathways may manifest clinically as slow
walking speed, weakness, weight loss, physical inactivity, and exhaustiondtermed the phenotype of frailty. CRP ¼ C-reactive protein; IL ¼ interleukin; TNF ¼ tumor necrosis
factor.
JACC Vol. 63, No. 8, 2014 Afilalo et al. 749
March 4, 2014:747–62 Frailty in Cardiovascular Care

testosterone levels (11,12), and insulin resistance (13). This scales. The gait speed test has been shown to have excel-
leads to a catabolic milieu, in which muscle breakdown ex- lent inter-rater reliability (intraclass coefficient 0.88 to 0.96)
ceeds muscle building, leading to a progressive decline in and test-retest reliability (intraclass coefficient 0.86 to 0.91)
muscle mass and strength (sarcopenia) (14). Under stressed (27). It is responsive to change, with meaningful improve-
conditions, subclinical impairments are unmasked, and a ments in gait speed (estimated at 0.05 to 0.2 m/s [28,29])
vicious cycle ensues with physical inactivity and malnutrition predicting positive outcomes on a population level (30) but
leading to further decline (15,16) (Fig. 1). not necessarily an individual patient level (31). The walking
The pathobiology of frailty and CVD shares several distance has varied between 3 and 10 m, although the dis-
commonalities, particularly a consistent correlation with the tance has little effect on measured speed (32). The 5-m
inflammatory biomarkers interleukin-6 and C-reactive pro- distance has been adopted by large registries and is a good
tein. Just as immune cells and cytokines exert nefarious ef- balance between allowing patients to achieve a steady
fects on the arterial wall to promote atherosclerosis, so too walking speed without eliciting cardiopulmonary symptoms.
do they impact cellular senescence and body composition to The short distance and comfortable pace are well below
promote frailty. Moreover, by causing impairments in cardiopulmonary limitations, making the focus of this test
multiple organ systems, subclinical CVD is one of the different than a typical stress test or 6-min walk test.
important contributors to frailty (17). This biological link The aforementioned tools reflect the clinical phenotype
frames the epidemiological data, showing that frailty and of frailty; another school of thought reflects the accumu-
CVD coexist in a large number of individuals (18). lation of deficits (33). Deficits encompass an assortment of
up to 70 symptoms, signs, comorbidities, disabilities, and
Frailty Assessment Tools frailty traits, which are counted and summed. A simplified
bedside version has been developed (34). The International
Upward of 20 frailty tools have been developed to measure Academy on Nutrition and Aging Frailty Task Force (35)
frailty (19); owing to a lack of consensus agreement, there is favored the clinical phenotype approach, stating that
variability among studies and confusion on which tool to comorbidities and disabilities should be disentangled from
use. Most tools focus on 1 or more of the 5 core domains frailty.
that define the frailty phenotype: slowness, weakness, low Disabilities, broadly defined as difficulty or dependency in
physical activity, exhaustion, and shrinking. Slowness is carrying out activities of daily living (ADL) or instrumental
measured by a comfortable-pace gait speed test, weakness by ADL, are erroneously interchanged with “frailty” in many
a maximal handgrip strength test (using a dynamometer), instances. However, disability is more correctly conceptual-
and other domains by questionnaire or more specialized ized as an adverse outcome associated with frailty (e.g., a frail
instruments. These domains may be considered individually patient becomes disabled after a myocardial infarction) or as
or combined into a variety of scales (Table 1). a separate entity altogether (e.g., a nonfrail patient becomes
The Fried scale (20) encompasses slowness, weakness, low disabled after a motor vehicle accident).
physical activity, exhaustion, and shrinking (unintentional Patient heterogeneity precludes the use of a “one size fits
weight loss), with 3 of 5 criteria required for a diagnosis of all” scale and cutoff for frailty. There is a ceiling effect
frailty. This is the most frequently cited frailty scale and has when physical performance scales such as the SPPB are
been demonstrated to predict mortality and disability in administered to healthier individuals (more challenging
large cohorts of community-dwelling elders and patients versions are available) (36), and conversely there is a floor
with CVD. Whether cognition and mood should be effect when the scales are administered to debilitated hos-
considered as the sixth and seventh domains of frailty or as pitalized patients (up to 30% have a score of 0). Certain
modulating factors (i.e., catalyzing the transition from frailty scales may be effective to screen for frailty, whereas others
to overt disability) remains an area of discussion (1,21). may be required to focus on specific and potentially treat-
The Short Physical Performance Battery (SPPB) (22,23) able domains. There is justifiable reason to consider various
encompasses slowness, weakness, and balance. This is scales, more/less challenging variants of such scales, or
measured by a series of 3 timed physical performance tests different cutoffs to define frailty depending on the popu-
(gait speed, chair rises, and tandem balance), each is scored lation being studied.
0 to 4 and a total score 5 of 12 is required for a diagnosis of
frailty.
In contrast to these multi-item frailty scales, 5-m gait
Frailty in CVD: Current Body of Evidence
speed, and to a lesser extent handgrip strength, has been The prevalence of frailty in community-dwelling older
advocated as a single-item measure of frailty (24–26) that adults is estimated to be 10% (37), and depending on the
often outperforms more elaborate and time-consuming population studied and the frailty assessment tool used, rises
 750
Frailty in Cardiovascular Care
Afilalo et al.
Table 1

Recommended Frailty Assessment Tools

Domain Tool(s) Operational Definition Common Cutoffs for Frailty

Slowness 5-m gait speed test Patient is positioned behind start line and asked to walk at a comfortable pace past 5-m finish line; cue to trigger Slow: <0.83 m/s (>6s)
stopwatch is first footfall after start line and first footfall after finish line; repeated 3 times and averaged Very slow: <0.65 m/s (>7.7 s)
Extremely slow: <0.50 m/s (>10 s)

Weakness Handgrip strength test Patient is asked to squeeze a handgrip dynamometer as hard as possible; repeated 3 times (once with each hand Men: <30 kg
and then with strongest hand); maximum value is recorded Women: <20 kg

Knee extensor Patient is seated on the dynamometer machine and asked to extend his/her knee against resistance; maximum isotonic Frailty cutoffs not yet established
strength test force is recorded

Low physical Physical activity Many questionnaires have been validated; those that provide a measure of activity in kcal/week Men: <383 kcal/week
activity questionnaire are recommended (e.g., Minnesota Leisure Time Activity, PASE, Paffenbarger Physical Activity Women: <270 kcal/week
Questionnaire)

Portable accelerometer Patient is asked to wear a portable accelerometer for a period of 1 to 7 days; total kcal expenditure is recorded Frailty cutoffs not yet established

Exhaustion CES-D questionnaire Patient is asked 2 questions: How often in the past week did you feel like everything you did was an effort?/like Positive if often is the answer to
you could not get going? (often [i.e., 3 days] or not often [i.e., 0–2 days]) either question

Anergia questionnaire Patient is asked 7 questions pertaining to lack of energy over the past month Positive if major criterion “sits around a lot for
lack of energy” þ any 2 of 6 minor criteria

Shrinking Weight loss Self-reported or measured unintentional weight change not due to dieting or exercise 10 lbs in past year

Appendicular Measured muscle mass in arms and legs using a dual-energy x-ray absorptiometry scan Frailty cutoffs not yet established; general
muscle mass cutoffs >2 SD from controls
Men: 7.23 kg/height in m2
Women: 5.67 kg/height in m2

Serum albumin Measured serum albumin 3.3 g/dl

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JACC Vol. 63, No. 8, 2014

March 4, 2014:747–62
 JACC Vol. 63, No. 8, 2014 Afilalo et al. 751
March 4, 2014:747–62 Frailty in Cardiovascular Care

to 10% to 60% in older adults with CVD (18). In CVD,

frailty confers a 2-fold increase in mortality, an effect that
persists even after adjustment for age and comorbidities. The
relevance and impact of frailty has been demonstrated across

Frail if Composite score 5/12

8.3–11.5 s (0.44–0.60 m/s)
side by side 0–9 s or unable

Frail if Composite score 3/5

6.5–8.2 s (0.61–0.77 m/s)
a broad spectrum, including: 1) stable CVD; 2) subclinical
Scoring

11.6 s (0.43 m/s)

6.4 s (0.78 m/s)

CVD; 3) heart failure; 4) coronary syndromes; 5) cardiac

Each item is scored 0–4

Each item is scored 0–1

unable to walk 5 m
full tandem 0–2 s
full tandem 3–9 s
side by side 10 s

full tandem 10 s

surgery; and 6) transcatheter aortic valve replacement

13.7–16.6 s
11.2–13.6 s

(TAVR). These studies are outlined in Table 2 and are

16.7 s

11.1 s
unable

discussed in the following text.

¼

¼
¼
¼
¼
¼

¼
¼
¼
¼

¼
¼
¼
¼
0
1
2
3
4

0
1
2
3
4

0
1
2
3
4

Stable CVD in the Community

Beyond the cross-sectional association between frailty and

his/her chest; time to complete 5 chair rises is recorded (cue to stop stopwatch is when patient is standing after fifth chair rise)

CVD, the Women’s Health Initiative Study revealed that

Patient is seated on a straight-backed chair and asked to stand up 5 times as quickly as possible with arms folded across

women with coronary artery disease (CAD) were more

likely to develop de novo frailty over 6 years (12% vs. 5%)
Patient is asked to stand in semitandem position for 10 s; if patient is able, then he/she is asked to stand in full
tandem position for 10 s; if patient is not able, then he/she is asked to stand in side-by-side position for 10 s

(38), and the Health ABC (Health, Aging, and Body

Composition) study showed that older adults with
objectively-measured frailty were more likely to develop
CAD events (3.6% vs. 2.8% per year) (39). Furthermore,
the 3C (Three-City) Study showed that slow gait speed
was highly predictive of cardiovascular mortality (hazard
ratio [HR]: 2.9) but not mortality from cancer or other
Operational Definition

causes (HR: 1.0) (25). The EPESE (Established Pop-

ulations for Epidemiologic Studies of the Elderly) Study
similarly showed that impaired mobility was predictive of
CAD-related mortality (relative risk [RR]: 1.8 to 2.2), with
the RR increase being equivalent in magnitude to diabetes
(40). In 2 studies focusing on peripheral arterial disease,
frailty predicted cardiovascular mortality (HR: 2.6 to 11.0)
more so than all-cause mortality (HR: 1.9 to 2.9) (41,42).
Studenski et al. (43) performed a patient-level meta-
CES-D ¼ Center for Epidemiologic Studies Depression Scale; PASE ¼ Physical Activity Scale for the Elderly.

analysis of 9 large prospective studies and found that

for every 0.1 m/s increase in gait speed, there was a 10%
improvement in survival. Short-distance gait speed was
As described above

As described above

a robust yet simple “indicator of vitality that integrates

known and unrecognized disturbances in multiple organ
systems many of which affect survival.” Those who walked at
a speed of 0.8 m/s were predicted to reach an average life
expectancy, whereas those who walked >1.0 m/s exceeded
the average life expectancy (traffic signals at crosswalks are
Physical activity questionnaire

typically set at a pedestrian walking speed of 1.2 m/s,

Handgrip strength test
Components

CES-D questionnaire

reflecting the expected lower limit for ambulatory citizens).

5-m gait speed test

5-m gait speed test

Chair rise test
Balance test

Weight loss

Subclinical CVD

Before frail patients manifest clinical CVD, they tend to

exhibit subclinical cardiovascular derangements. A seminal
Table 1 Continued

Performance

substudy from the Cardiovascular Health Study screened for

Short Physical

Fried scale
Scale

Battery

subclinical CVD in 4,735 older adults and found that those

who were frail had an increased prevalence of undiagnosed/
subclinical lesions: myocardial injury on echocardiography,
 752
Table 2

Frailty in Cardiovascular Care

Afilalo et al.
Systematic Review of Frailty in Cardiovascular Disease
First Author, Year (Ref. #) N Design Frailty Tool % Frail Main Outcome(s) for Frail vs. Nonfrail

Community dwelling

Studenski, 2011 (43) 34,485 Meta-analysis of elderly in the community Gait speed (2.4–6 m) 32% 12-yr mortality: HR: 0.90 (95% CI: 0.89–0.91) per 0.1-m/s
increase in gait speed

Dumurgier, 2009 (25) 3,208 Prospective cohort of elderly in the Fast-pace gait speed (6 m) Lowest third 5.1-yr mortality: 19% vs. 10 %; HR: 1.4 (95% CI: 1.0–2.0)
*
(Three-City Study) community HR: 2.92 for cardiovascular mortality
vs. HR: 1.03 for cancer mortality

Corti, 1996 (40) 4,116 Prospective, multicenter cohort of Inability to walk 0.5 miles or 25% 4-yr CAD mortality:
elderly in the community 1 flight of stairs Men 3.5%/yr vs. 1.3%/yr; RR: 1.8 (95% CI: 1.1–3.0)
Women 1.9%/yr vs. 0.6%/yr; RR: 2.2 (95% CI: 1.5–3.5)
4-yr incident CAD:
Men 5.8% vs. 4.5% per yr; RR: 1.2 (95% CI: 0.7–2.1)
Women 5.1% vs. 2.5% per yr; RR: 1.6 (95% CI: 1.3–2.1)

Chin A Paw, 1999 (103) 450 Prospective, multicenter cohort of Chin A Paw scale 13% Prevalent CVD: 62% vs. 28%
elderly men in the community 3-yr mortality: 50% vs. 18%; OR: 4.1 (95% CI: 1.8–9.4)

Klein, 2005 (104) 2,515 Prospective, multicenter cohort of Klein scale (level 1–4) 53–64 yrs: 0.7% Prevalent CVD:
elderly and nonelderly in the 65–74 yrs: 5% Men: OR: 1.33 (95% CI: 1.06–1.67) per level
community 75–84 yrs: 22% Women: OR: 1.43 (95% CI: 1.13–1.82) per level
85 yrs: 53% 4-yr mortality: HR: 1.56 (95% CI: 1.27–1.92) per level

Woods, 2005 (38) 40,657 Prospective, multicenter cohort of Modified Fried scale 3 16% Prevalent frailty with vs. without CAD: 17% vs. 7%
(Women’s Health elderly women in the community Incident frailty with vs. without CAD: 12% vs. 5%;
Initiative Observational OR: 1.40 (95% CI: 1.11–1.76)
Study) 5.9-yr mortality: OR: 1.71 (95% CI: 1.48–1.97)

Chaves, 2005 (105) 670 Prospective, multicenter cohort of Fried scale 3 14% Prevalent CVD: 41% vs. 21%
(Women’s Health and elderly women in the community
Aging Studies I & II)

Bandeen-Roche, 2006 (106) 786 Prospective, multicenter cohort of Fried scale 3 11% 3-yr mortality: HR: 6.0 (95% CI: 3.0–12.1)
(Women’s Health and elderly women in the community 3-yr severe ADL disability: HR: 15.8 (95% CI: 5.8–42.8)
Aging Studies I & II) 3-yr nursing home placement: HR: 24.0
(95% CI: 4.5–129.2)

Newman, 2006 (39) 3,075 Prospective, multicenter cohort of Gait speed (400 m) N/A Incident CVD: slowest Q 3.6%/yr vs. fastest Q 2.8%/yr;
(Health ABC Study) elderly in the community HR: 1.61 (95% CI: 1.05–2.45)
5-yr mortality: slowest Q 4.0%/yr vs. fastest Q 1.4%/yr;
HR: 3.23 (95% CI: 2.11–4.94)

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March 4, 2014:747–62
Continued on the next page
Table 2 Continued

March 4, 2014:747–62
JACC Vol. 63, No. 8, 2014
First Author, Year (Ref. #) N Design Frailty Tool % Frail Main Outcome(s) for Frail vs. Nonfrail

Subclinical CVD

Newman, 2001 (44) 4,735 Cross-sectional study of elderly in the Fried scale 3 6% Prevalent clinical CVD: 38% vs. 17%; OR: 2.79
(Cardiovascular community (95% CI: 2.12–3.67)
Health Study) Prevalent subclinical CVD: RWMA, LVH, pre-HTN, low ABI,
carotid stenosis, silent CVA

Elbaz, 2005 (45) 2,572 Prospective, multicenter cohort of Fast pace gait speed (6 m) Lowest third CIMT >0.785 mm: mean gait speed 1.47 m/s (vs. 1.61 m/s
elderly and nonelderly in the community in CIMT 0.6 mm); OR: 1.9 (95% CI: 1.4–2.8)
Carotid plaques: mean gait speed 1.50 m/s (vs. 1.57 m/s
in no plaque group); OR: 1.3 (95% CI: 1.0–1.7)

Singh, 2012 (41) 3,571 Prospective, multicenter cohort of Modified Fried scale 3 6.4% all Prevalent frailty with vs. without PAD: 18% vs. 5%; OR: 2.31
(NHANES) elderly in the community, focus on those 17.5% ABI <0.9 (95% CI: 1.08–4.94)
with PAD (PAD) 4.9-yr mortality in PAD patients: 52% vs. 21%; HR: 2.88
(95% CI: 1.40–5.96)
4.9-yr CVD mortality in PAD patients: 29% vs. 6%;
HR: 11.02 (95% CI: 3.41–35.60)

McDermott, 2008 (42) 444 Prospective multicenter cohort of patients Gait speed <0.76 m/s Lowest quartile 4.8-yr mortality: HR: 1.87 (95% CI: 1.06–3.30)
(Walking and Leg with PAD (ABI <0.9) (4 m); SPPB 4.8-yr CVD mortality: HR: 2.59 (95% CI: 1.04–6.44)
Circulation Study)

Cardiac surgery

Afilalo, 2010 (63) 131 Prospective, multicenter cohort of Gait speed <0.83 m/s 46% In-hospital mortality/morbidity: 35% vs. 13%; OR: 3.05
(Frailty ABCs Study) elderly patients undergoing cardiac (5 m) (i.e., >6 s to walk 5 m) (95% CI: 1.23–7.54)
surgery Discharge to facility: 46% vs. 20%; OR: 3.19
(95% CI: 1.40–8.41)

Afilalo, 2012 (67) 152 Prospective, multicenter cohort of Gait speed <0.83 m/s (5 m) 46% In-hospital mortality/morbidity:
(Frailty ABCs Study) elderly patients undergoing cardiac Fried scale 3 20% Gait speed: AUC 0.68
surgery Expanded Fried 3 Fried: AUC 0.60
MSSA subdimensions Expanded Fried: AUC 0.58
MSSA subdimensions: AUC 0.56

Lee, 2010 (64) 3,826 Retrospective cohort of elderly and Ambulation dependence, 4% In-hospital mortality: 15% vs. 5%; OR: 1.8 (95% CI:1.1–3.0)
nonelderly patients undergoing ADL disability, or diagnosis 2-yr mortality: 30% vs. 11%; OR: 1.5 (95% CI: 1.1–2.2)
cardiac surgery of dementia Discharge to facility: 49% vs. 9%; OR: 6.3
(95% CI: 4.2–9.4)

Sündermann, 2011 (65) 400 Prospective cohort of elderly patients CAF score 11 50% 30-day mortality: 10% vs. 4%; AUC 0.71
undergoing cardiac surgery (43% moderate,

Frailty in Cardiovascular Care

8% severe)

Sündermann, 2011 (66) 213 Prospective cohort of elderly patients CAF score 11 54% 1-yr mortality: OR: 1.11 (95% CI: 1.04–1.16) per point
undergoing cardiac surgery (45% moderate,
9% severe)

Robinson, 2011 (76) 223 Prospective cohort of elderly patients Timed up-and-go 15 s 30% Discharge to facility: 67% vs. 8%; OR: 13.0

Afilalo et al.
undergoing major surgery (34% cardiac (95% CI: 5.1–33.0)
surgery)

Lee, 2011 (107) 262 Prospective cohort of elderly patients Cross-sectional area of N/A 90-day mortality: HR: 0.33 (95% CI: 0.16–0.68)
undergoing abdominal aortic psoas muscles at L4 by per 1,000-mm2 increase in muscle area
aneurysm surgery computed tomography 1-yr mortality: 9% tertile 1 vs. 5% tertile 3
3-yr mortality: 21% tertile 1 vs. 13% tertile 3

753
Continued on the next page
Table 2 Continued

754
First Author, Year (Ref. #) N Design Frailty Tool % Frail Main Outcome(s) for Frail vs. Nonfrail

TAVR

Frailty in Cardiovascular Care

Afilalo et al.
Rodés-Cabau, 2010 (70) 345 Retrospective, multicenter cohort Subjective judgment of 25% Procedural complications: no differences except need for
of patients undergoing TAVR treating physician dialysis 7% vs. 1% (p ¼ 0.009)
30-day mortality: 8% vs. 11% (p ¼ 0.54)
8-month mortality: 22% vs. 22% (p ¼ 1.00)

Ewe, 2011 (69) 147 Prospective, multicenter cohort Fried scale 3 33% 9-month mortality/morbidity: HR: 4.2 (95% CI: 2.0–8.8)
of patients undergoing TAVR

Green, 2012 (71) 102 Cross-sectional study of TAVR (83%), high-risk Gait speed <0.5 m/s (4.6 m) 63% Prevalent ADL disability: OR: 1.52 (95% CI: 1.21–1.91)
AVR (11%), and medically managed AS (5%) per 0.1 m/s; AUC 0.81

Green, 2012 (72) 159 Prospective cohort of patients undergoing TAVR Modified Fried scale >median 50% 30-day mortality/morbidity: nonsignificant
1-yr mortality: 17% vs. 7%; HR: 3.51 (95% CI: 1.43–8.62)

Schoenenberger, 2012 119 Prospective cohort of patients undergoing TAVR In-house scale 3/7 50% 6-month ADL change 1: 31.3% vs. 12.1% (OR: 3.34 for
(73) functional decline; OR: 4.21 for functional decline or
death, adjusted for STS)
6-month mortality: 18.6% vs. 3.3%

Stortecky, 2012 (74) 100 Prospective cohort of patients undergoing TAVR In-house scale 3/7 49% 1-yr mortality: OR: 2.93 (95% CI: 0.93–9.24)
(same cohort as Schoenenberger) 1-yr major cardiovascular and cerebral events:
OR: 4.89 (95% CI: 1.64–14.60); both adjusted for STS

Coronary disease

Purser, 2006 (57) 309 Prospective cohort of elderly patients with Fried scale 3 27% 6-month mortality:
severe CAD admitted to cardiac unit Rockwood scale 1 63% Fried: 12% vs. 8%; OR: 1.9 (95% CI: 0.6–6.0)
Gait speed <0.65 m/s 50% Rockwood: 11% vs. 5%; OR: 1.4 (95% CI: 0.3–5.6)
Grip strength <25 kg 50% Gait speed: 14% vs. 4%; OR: 4.0 (95% CI: 1.1–13.8)
Chair rise <7/30 s 56% Grip strength: 13% vs. 5%; OR: 2.7 (95% CI: 0.7–10.0)
Chair rise: 12% vs. 5%; OR: 1.5 (95% CI: 0.4–5.0)

Ekerstad, 2011 (61) 307 Prospective, multicenter cohort of CSHA Clinical Frailty Scale 5 49% 30-day mortality/morbidity: 46% vs. 27%; OR: 2.17
elderly patients with NSTEMI admitted to (95% C1: 28–3.67)
cardiac or medical unit 30-day mortality: 15% vs. 3%; OR: 4.7
(95% CI: 1.7–13.0)

Singh, 2011 (58) 629 Prospective, multicenter cohort of Fried scale 3 21% 3-yr mortality: 28% vs. 6%; HR: 2.74
elderly patients post-PCI (95% CI: 1.12–6.71)

Gharacholou, 2012 (60) 629 Cross-sectional analysis of elderly patients Fried scale 3 21% SAQ: more physical limitation and lower QOL
post-PCI (same cohort as Singh) (despite same angina frequency)
SF-36: lower PCS and MCS scores

McNulty, 2011 (59) 101 Retrospective, multicenter cohort of elderly Subjective judgment of treating 7% 1.5-yr mortality: unadjusted HR: 14.0
and nonelderly patients post–left main PCI physician (“cachexia/frailty”) (95% CI: 5.4–36.0)

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Continued on the next page

March 4, 2014:747–62
Table 2 Continued

March 4, 2014:747–62
JACC Vol. 63, No. 8, 2014
First Author, Year (Ref. #) N Design Frailty Tool % Frail Main Outcome(s) for Frail vs. Nonfrail

Heart failure

Cacciatore, 2005 (53) 120 Secondary analysis of cohort study of Lachs frailty staging system 15% 12-yr mortality: 94% vs. 69%; HR: 1.62
elderly patients with chronic heart failure (95% CI: 1.08–2.45)

Altimir, 2005 (108) 360 Cross-sectional study of elderly patients with Altimir scale 42% Prevalent frailty: 42%
chronic heart failure referred to HF clinic

Lupón, 2008 (49) 622 Prospective cohort of elderly patients with Altimir scale 40% MLWHFQ: 39 vs. 19 (p < 0.001)
chronic heart failure referred to HF clinic HF hospitalization: 21% vs. 13% (p ¼ 0.01)
1-yr mortality: 17% vs. 5%; HR: 2.09
(95% CI: 1.11–3.92)

Volpato, 2008 (54) 92 Prospective cohort of acute patients admitted to SPPB admission, discharge N/A Length of stay: þ2.5–4 days for SPPB 0–4 on
hospital (64% decompensated heart failure) admission (þ0.5 day for every SPPB point)

Volpato, 2011 (55) 87 Prospective cohort of acute patients admitted to SPPB admission, discharge, N/A Incident disability: þ0.24 ADL limitations for SPPB
hospital (64% decompensated heart failure) 1 month 0–4 at discharge or SPPB decline at follow-up
1-yr mortality or hospitalization: 75% vs. 57%;
OR: 5.38 (95% CI: 1.82–15.9) for SPPB 0–4 vs. 5–12;
HR: 3.59 (95% CI: 1.20–10.0) for SPPB decline
at follow-up

Chiarantini, 2010 (56) 157 Prospective, multicenter cohort of patients SPPB 51% 15-month mortality:
with decompensated heart failure SPPB 0: 62 per 100 PY; HR: 6.06 (95% CI: 2.19–16.76)
discharged from cardiac unit SPPB 1–4: 29 per 100 PY; HR: 4.78
(95% CI: 1.63–14.02)
SPPB 5–8: 17 per 100 PY; HR: 1.95
(95% CI: 0.67–5.70)
SPPB 9–12: 9 per 100 PY; HR: 1 (referent)

Tjam, 2012 (109) 149 Secondary analysis of cohort study of RAI 2.0 scale N/A 6-month mortality: AUC 0.87
elderly patients with chronic heart failure
living in long-term care

Khan, 2013 (49) 2,825 Prospective, multicenter cohort of Modified SPPB 2 31% 11-yr incident HF: HR: 1.30 (95% CI: 1.10–1.55)
(Health ABC Study) elderly in the community without baseline *Overall incidence 15.9% or 1.8 per 100 PY
heart failure

Chaudhry, 2013 (110) 758 Prospective, multicenter cohort of Gait speed <0.8 m/s (4.6 m) 42% 3.4-yr hospitalization: Gait speed: adjusted
(Cardiovascular Health Study) elderly in the community with newly Grip strength: men: <28.5 kg; HR: 1.28 (95% CI: 1.06–1.55)
diagnosed heart failure women: <18.5 kg Grip strength: adjusted HR: 1.19 (95% CI: 1.00–1.42)

Frailty in Cardiovascular Care

Rozzini, 2003 (111) 995 Prospective cohort of acute patients Barthel ADL <90 20% 6-month mortality: 28% vs. 12% vs. 4% if both, either,
admitted to cardiac unit MMSE <18 or neither criteria present

ABI ¼ ankle-brachial index; ADL ¼ activities of daily living; AS ¼ aortic stenosis; AUC ¼ area under curve; AVR ¼ aortic valve replacement; CAD ¼ coronary artery disease; CAF ¼ Comprehensive Assessment of Frailty; CIMT ¼ carotid intima media thickness; CSHA ¼ Canadian
Study of Health and Aging; CVA ¼ cerebrovascular accident; CVD ¼ cardiovascular disease; Health ABC ¼ Health, Aging, and Body Composition; HF ¼ heart failure; HR ¼ hazard ratio; HTN ¼ hypertension; LVH ¼ left ventricular hypertrophy; MCS ¼ mental component
summary; MLWHFQ ¼ Minnesota Living With Heart Failure Questionnaire; MMSE ¼ Mini-Mental Status Examination; MSSA ¼ MacArthur Study of Successful Aging; NHANES ¼ National Health and Nutrition Examination Survey; NSTEMI ¼ non–ST-segment elevation

Afilalo et al.
myocardial infarction; OR ¼ odds ratio; PAD ¼ peripheral artery disease; PCI ¼ percutaneous coronary intervention; PCS ¼ physical component summary; PY ¼ person-years; QOL ¼ quality of life; RAI ¼ Resident Assessment Instrument; RR ¼ relative risk; RWMA ¼ regional
wall motion abnormality; SAQ ¼ Seattle Angina Questionnaire; SF-36 ¼ Short-Form 36; SPPB ¼ Short Physical Performance Battery; STS ¼ Society of Thoracic Surgeons; TAVR ¼ transcatheter aortic valve replacement.

755
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Frailty in Cardiovascular Care March 4, 2014:747–62

brain infarcts on magnetic resonance imaging, abnormal SPPB to patients with recently decompensated heart failure
ankle-brachial index, carotid stenosis, pre-hypertension, and at different time points (shortly after admission, at discharge,
left ventricular hypertrophy (44). A subanalysis from the 3C and 1 month after discharge). A low SPPB score on
Study showed that those who had slow gait speed were more admission was associated with prolonged length of stay,
likely to have carotid intimal-medial thickening and silent whereas a low SPPB score at discharge was associated with
carotid plaques (45). Subclinical CVD predisposes to “un- a higher risk of ADL disability, mortality, or readmission
successful aging” (46), often defined as impaired physical or (odds ratio [OR]: 5.4). In a similar study by Chiarantini
cognitive functioning and development of clinically manifest et al. (56), the yearly mortality rates were 62%, 45%, 17%,
disease (47). and 9% for SPPB scores of 0, 1 to 4, 5 to 8, and 9 to 12,
respectively. The SPPB was responsive to change, with
Heart Failure 63% improving versus 20% worsening from admission to
discharge and 50% improving versus 18% worsening from
Frailty is pertinent to the development, manifestations, and
discharge to 1 month.
prognosis of heart failure. Frailty may be apparent at the
myocardial organ level by predisposing patients to a greater Acute Coronary Syndromes and
extent of myocardial injury and, thus, clinical heart failure in Percutaneous Coronary Interventions
response to stressors such as coronary ischemia or pressure or
volume overload. Alternatively, frailty may be apparent at In a seminal study of 309 elderly patients admitted to a
the global multisystem level by predisposing patients with coronary care unit and found to have multivessel CAD,
heart failure to decompensate at a lower threshold and Purser et al. (57) found that the prevalence of frailty varied
require more frequent hospitalizations. The person-years considerably depending on the tool used: 27% with the Fried
accrued for studies of frailty in the heart failure setting are scale, 50% with gait speed <0.65 m/s, and 63% with the
greater than those for other cardiac conditions, involving Rockwood scale. Each tool was associated with a trend to-
approximately 2,300 patients with heart failure and up to 12 ward increased 6-month mortality, yet only gait speed was
years of follow-up. statistically significant (OR: 4.0).
The Health ABC Study followed 2,825 older patients free In a study of 629 elderly patients who underwent percu-
of baseline heart failure over a period of 11 years and found taneous coronary intervention at the Mayo Clinic, the
that frailty (as measured by a modified SPPB) conferred a prevalence of frailty was 21% with the Fried scale adminis-
30% higher risk of developing new heart failure (48). tered before discharge, conferring a significant increase
Excluding heart failure events in the first year did not alter in 3-year mortality (28% vs. 6%; OR: 2.74) (58). Similarly,
the results, implying that frailty was not merely capturing “cachexia/frailty” was the most powerful predictor of
undiagnosed/imminent cardiac dysfunction. 18-month mortality (HR: 14.0) (59) in a study of 111 pa-
Although traditionally considered a geriatric condition, tients undergoing percutaneous coronary intervention for
frailty was found by Lupón et al. (49) in one-third of unprotected left main disease in the Kaiser Permanente
younger patients with heart failure. Because chronic heart database.
failure is known to perturb skeletal muscle and body Gharacholou et al. (60) further showed that, despite a
composition (50,51) (giving rise to the phenotype of “cardiac similar severity of angina between frail and nonfrail
cachexia” in extreme cases), it is not surprising to observe patients, those who were frail had lower physical functioning
a large proportion of younger and older patients with heart and quality of life. Frailty exerted a greater impact on quality
failure exhibiting frailty traits. of life than comorbidities. Ekerstad et al. (61) explored the
Patients with chronic heart failure who were frail had relationship between frailty and comorbidities in patients
a higher risk of mortality at 1 year (17% vs. 5%), heart failure with non–ST-segment elevation myocardial infarction and
hospitalizations (21% vs. 13%), and impaired quality of life showed that 79% of frail patients had at least 1 severe co-
(49). Chaudhry et al. (52) showed that slow gait speed was morbidity. The OR for frailty to predict mortality was
the most powerful predictor of hospitalizations, conferring exponentially higher when the comorbidity burden was
a 30% increase; weak grip strength was also predictive, moderate to severe.
conferring a 16% increase. In a long-term study by The studies of Ekerstad, Purser, and Lupón all showed
Cacciatore et al. (53), patients with chronic heart failure who that frail patients were less aggressively managed compared
were frail had a substantially lower probability of surviving with their nonfrail counterparts; whether this is for better or
>10 years (6% vs. 31%). for worse remains unclear. They were less likely to receive
Frailty is also relevant in acute decompensated heart angiotensin-converting enzyme inhibitors (71% vs. 81%)
failure. Volpato et al. (54,55) succeeded in administering the and beta-blockers (63% vs. 80%), less likely to be admitted
JACC Vol. 63, No. 8, 2014 Afilalo et al. 757
March 4, 2014:747–62 Frailty in Cardiovascular Care

to a coronary care unit (35% vs. 54%), and less likely to be patients are less likely to be referred for such a surgery.
referred for cardiac catheterization (15% vs. 46%) or coro- Therefore, disability scales for basic ADL are insensitive to
nary artery bypass surgery (9% vs. 16%). screen elderly patients in this context. Higher-level disability
scales such as the Nagi scale are more sensitive and better
Cardiac Surgery predict outcomes. An interaction between frailty and
disability has been reported, with the prognostic effect of
Cardiac surgery is an inherently relevant setting for frailty
frailty diminishing in patients who have progressed to the
because surgery represents an iatrogenic physiological
more advanced stage of disability (67).
stressor to which the patient’s resiliency will determine their
In addition to predicting post-operative mortality and
post-operative course. Surgeons have been performing de
morbidity, 3 studies showed that frail patients were less
facto clinical frailty assessments termed the “eyeball test” or
likely to be discharged home and were more likely to require
the “end of the bed-o-gram” for quite some time. More
rehabilitation and/or institutionalization after cardiac surgery
recently, investigators have examined the role of objective
(OR: 3.2 to 13.0).
frailty tools to predict post-operative outcomes, and even the
Thus, it is evident that frail patients who undergo cardiac
lay media has been attracted by this prospect (62). The
surgery have higher rates of post-operative mortality,
utility of frailty to prospectively guide surgical decisions and
morbidity, prolonged length of stay, and need for discharge
improve outcomes has yet to be explicitly tested.
to facilities. It is not evident whether frail patients who
The Frailty ABCs (Frailty Assessment Before Cardiac
undergo less invasive intervention (or no intervention) have
Surgery) prospective study showed that slow 5-m gait speed
improved outcomes, although this is at times extrapolated.
was associated with a 3-fold increase in post-operative
For the time being, a more prudent extrapolation may be
mortality or major morbidity (OR: 3.1) (63). A walking
that the risks and benefits of cardiac surgery should
time of 6 s or longer (<0.83 m/s) was selected as the optimal
be carefully weighed in frail patients, ideally with a multi-
cutoff based on receiver-operating characteristic analysis.
disciplinary heart team, and if indicated, should proceed
Importantly, gait speed contributed incremental value above
with thorough pre-operative optimization and heightened
the Society for Thoracic Surgeons risk score (area under the
post-operative surveillance.
curve 0.70 for risk score alone vs. area under the curve 0.74
for risk score plus gait speed). Patients with slow gait speed Transcatheter Aortic Valve Replacement
and a high risk score had a 43% incidence of mortality/
morbidity, whereas those with normal gait speed and a low TAVR was initially developed for patients with severe aortic
to intermediate risk score had a 6% incidence. There was stenosis (AS) who were considered “too frail for surgery;”
a trend toward interaction for female patients and those thus, the concept of frailty has been intimately linked to
undergoing aortic valve replacement (AVR), both of which TAVR. Patients referred for TAVR typically have advanced
had a markedly greater RR when frailty was present. age, multiple comorbidities, and a prevalence of frailty as
Studies by Lee et al. (64) and Sündermann et al. (65,66) high as 63%. Frailty is 1 of the “missing parameters” not
showed that pre-operative frailty was associated with post- captured by traditional risk scores (68) that are relied upon
operative mortality at 30 days and 1 to 2 years. These by clinicians as gatekeepers to TAVR. Few studies have been
2 studies differed in the frailty scales used, and as a result, in published in the past 2 years, limited to approximately 100
the reported prevalence of frailty. Lee et al. (64) retrospec- to 150 patients each, and larger studies are underway.
tively reviewed data from the Maritime Heart Center Cardiac Although this was not the primary aim of their study,
Surgery Registry and defined frailty as ambulation depen- Ewe et al. (69) found that one-third of patients undergoing
dence, ADL disability, or diagnosed dementia. This defini- TAVR were frail according to the Fried scale and that frailty
tion represented disability more than frailty and yielded a low was among the most powerful predictors of death, myocar-
4% prevalence of frailty (mixed elderly and nonelderly dial infarction, stroke, or heart failure at 9 months (HR:
cohort). Sündermann et al. (65,66) defined frailty as an 4.2). Frailty was not a significant predictor when defined
aggregate of 35 criteria, which yielded a 50% prevalence of according to the physician’s subjective judgment in the
frailty. The data from Afilalo et al. (67) showed a 46% earlier study by Rodés-Cabau et al. (70).
prevalence of frailty using gait speed versus 20% using the Green et al. (71,72) presented the experience at Columbia
Fried scale and a low 5% prevalence of ADL disability; the University and surprisingly showed that frailty was predictive
single measure of gait speed outperformed other scales in of 1-year mortality (17% if frail vs. 7% if not frail; HR: 3.5)
predicting outcomes. but not the composite of 30-day mortality or morbidity. The
The presence of frank disability is infrequent in the lack of 30-day event prediction was attributed to “adequacy of
general cardiac surgery population, in part because disabled the standard selection process,” although it should be noted
758 Afilalo et al. JACC Vol. 63, No. 8, 2014
Frailty in Cardiovascular Care March 4, 2014:747–62

that there was no systematic frailty assessment on patients of the transcatheter procedure mitigate this risk? In both
who had been screened out to substantiate the adequacy of cardiac surgery and TAVR, the rate of technical success
the selection process and the absolute number of events was remains high and the risk of intraprocedural mortality low in
low. Furthermore, the trends toward greater risk in frail frail patients.
patients (especially for major bleeding, major vascular com-
plications, and length of stay) were concerning. The increase
in C-statistic from 0.73 to 0.77 and the net reclassification The Use of Frailty in Clinical Practice
index of 0.24 were in the clinically meaningful range, yet There are many scenarios in day-to-day clinical practice in
confidence intervals were wide. which frailty assessment can contribute valuable prognostic
Between 19% and 35% of patients were unable to complete information and assist the clinicians in defining optimal care
the short-distance gait speed test. This is a sizeable propor- pathways for their patients. Ideally, frailty is not a reason
tion of nonwalkers, larger than the <10% generally reported to withhold care but rather a means of structuring care in a
for other cardiac cohorts, which may reflect the heavy burden more patient-centered fashion.
of comorbidity and disability in patients undergoing TAVR. A guiding principle is that frailty, disability, and comor-
Not being able to complete the gait speed test is an indicator bidity are inter-related but distinct entities (75). A second
of advanced frailty or perhaps even disability because non- principle is that there is no definitive gold standard test for
walkers have weaker grip strength, lower albumin levels, and frailty, but rather an assortment of tools that reflect 1 or more
more ADL disabilities. Low albumin levels and ADL dis- domains of frailty. Multidomain tools do not necessarily
abilities were the strongest predictors in their TAVR cohort. provide incremental value above single-domain tools, and ease
A gait speed of 0.50 m/s was selected as the optimal cutoff of implementation may be an important factor for adoption.
based on receiver-operating characteristic analysis, slower A third principle is that frailty is a continuous spectrum,
than the 0.65 to 0.85 m/s cutoffs reported for other cardiac and specific cutoffs used to dichotomize frailty status in 1
cohorts. The authors commented that >80% of their patients group of patients may not be applicable in another group.
would have been considered frail if these traditional cutoffs The tools recommended in Table 1 provide a (nonre-
had been used, supporting the notion that adapted cutoffs are strictive) framework to improve consistency and compara-
required to achieve reasonable discrimination. bility among studies. For investigators seeking to test new or
This is in slight contrast to the TAVR experience at Bern modified tools, they are encouraged to also use 1 of the
University (73,74), in which the vast majority of patients recommended tools as a comparator and to confirm the
were able to complete the timed-up-and-go test (which re- findings in a validation cohort before reporting.
quires standing up from a chair, walking 3 m, and turning
around) and 61% of patients were able to do so faster than High-Yield Clinical Scenarios for Assessment
the usual cutoff of 20 s. Their frailty scale consisted of of Frailty in Cardiovascular Medicine
timed-up-and-go, mobility limitation, basic ADL disability,
instrumental ADL disability, mini-mental status examina- Consideration for cardiac surgery. Frailty assessment tools
tion, and mini-nutritional assessment. Frailty was predictive should be employed in the pre-operative period; at a mini-
of a 3- to 4-fold increase in functional decline at 6 months mum, 5-m gait speed is a simple and powerful measure of
(measured by basic ADL disabilities) and major cardiac and frailty supported by prognostic data. However, it is prema-
cerebral adverse events at 1 year. There was a trend for frailty ture to assume that frailty should determine eligibility for
and all-cause mortality, which was stronger at 30 days surgery at the individual patient level. Until data are available
compared with 1 year, although the number of events was to prove a direct role for frailty in determining treatment, it
small. is recommended to integrate frailty with other proven risk
Synthesizing the evidence surrounding frailty in TAVR, factors and risk models for decision making.
2 critical questions arise: first, are the standard frailty The timing of frailty assessment may be in the inpatient
assessment tools (gait speed, even with adapted cutoffs, grip setting just before the surgery or in the outpatient setting,
strength, and Fried scale) valid in this severely ill and often providing there is no intercurrent change or prolonged delay
debilitated population or are these traits too ubiquitous, such (arbitrarily >1 month) between the assessment and surgery. The
that we should be relying on markers of more advanced choice of when to assess frailty tends to be logistically driven
frailty and frank disability (inability to walk, low albumin, depending on feasibility and work flow at the given center.
ADL disability) to better discriminate risk? Second, does Pre-operative optimization via a multidisciplinary approach
frailty increase the risk of short-term morbidity after TAVR is key to counteract the multiple physiological impairments
(as it does in cardiac surgery) or does the less invasive nature (e.g., cardiac, neurological, muscular, respiratory, renal) that
JACC Vol. 63, No. 8, 2014 Afilalo et al. 759
March 4, 2014:747–62 Frailty in Cardiovascular Care

lead to the decreased physiological reserve characteristic of Controversies and Future Research Questions
frailty (76). Establishing a heart team and involving the
appropriate consultants are instrumental in this regard. Defining the optimal tool set to measure frailty is a high
Prompt recognition and treatment of complications are pri- priority. We must first determine whether there is incre-
mordial; deconditioning and delirium are 2 complications that mental value in using multi-item scales such as Fried as
merit special attention because of their insidious and devas- opposed to single-item measures such as 5-m gait speed
tating course. Cardiac rehabilitation may potentially improve (57,67,78,79). We must also determine the appropriate
frailty, and although this has yet to be proven, may ultimately cutoff for each tool and patient group, particularly for gait
serve to facilitate surgical recovery for frail elderly patients. speed (>10 cutoffs have been proposed ranging from 0.5 to
Patients may benefit, for example, if cardiac rehabilitation is 1.0 m/s). This underscores the need to validate frailty tools
initiated before a planned procedure and then continued af- and cutoffs in the population of interest rather than
terward, with aerobic and strength training alongside nutri- extrapolating results from other studies.
tional and educational components. The ongoing FRAILTY-AVR multicenter study
(NCT01845207) is comparing different frailty tools to
Consideration for TAVR. Because patient selection con- determine which is most predictive in high-risk patients
tinues to be a central and often challenging issue, there is with AS undergoing AVR and TAVR. The Society for
hope that frailty can be used to pre-select high-risk patients Thoracic Surgeons Adult Cardiac Surgery Database is
with AS who are best served by TAVR rather than surgical collecting 5-meter gait speed data to define its
AVR. Proving this hypothesis has not been straightforward, value across a broad sample of patients undergoing
particularly because the majority of patients referred for cardiac surgery. The CoreValve U.S. pivotal trial and
TAVR are frail and the usefulness of frailty (or any other risk PARTNER II (Placement of Aortic Transcatheter Valves)
factor) becomes limited when it is endemic. Moreover, trial have integrated frailty assessment in all eligible patients.
because the TAVR procedure induces less physiologic stress The SILVER-AMI Trial (NCT01755052) is evaluating the
compared with surgery, it is unclear whether frailty will impact of frailty alongside other risk factors in older adults
predict post-procedural outcomes similarly in TAVR and hospitalized with acute myocardial infarction. Many other
surgery. CVD trials have begun considering frailty.
The role of frailty assessment in TAVR programs may There is an impetus to develop more robust frailty tools.
ultimately prove to be in identifying who is not frail and thus Existing tools are limited in the measurement of physical
appropriate for conventional AVR. At the other end of the activity and energy expenditure (80,81); portable pedom-
spectrum, the role of frailty assessment may be in identifying eters and actigraphy-based tools are being investigated for
who is extremely frail and/or disabled and thus appropriate this purpose (82). Whereas most tools capture muscle
for medical management without intervention. The latter strength, muscle mass is only indirectly measured by
patient typically exhibits 1 or more features of cachexia, weight loss. Weight loss is a flawed measure of muscle
severe weakness, inability to ambulate, dementia, and ADL mass because excess adiposity may mask low muscle
dependencies. Anecdotally, balloon aortic valvuloplasty has massdtermed “sarcopenic obesity” (83,84). In a study of
been used to allow for rehabilitation and improvements in elderly patients with cancer, 7.5% of patients were found to
heart failure as a bridge to TAVR. be underweight, whereas 46.8% were sarcopenic (85).
Stable or recently stabilized heart failure or CAD. Once Muscle mass is a predictor of frailty and functional decline
identified in the inpatient or outpatient setting, frail (86,87) and can be reliably measured by computed to-
patients may be excellent candidates for cardiac rehabilita- mography, magnetic resonance, or dual-isotope x-ray ab-
tion (targeting frail patients may be 1 strategy to overcome sorptiometry (88).
the underuse of cardiac rehabilitation in general), longitu- Exciting translational research is seeking to gain mecha-
dinal heart function clinics, and comprehensive geriatric nistic insights into the pathobiology of frailty and, in doing
assessment (77). The latter may include evaluation by ex- so, is fueling the development of frailty therapeutics and
perts in nutrition, physical function, cognition, psycho- elusive frailty biomarkers. Biomarkers of senescence such as
geriatrics, and social support; each of which represents an telomere length are not correlated with frailty (89). Other
area of potential vulnerability for frail patients and a blind biomarkers have been correlated with frailty but remain
spot for most cardiovascular practitioners who are not nonspecific: C-reactive protein, interleukin 6, tumor necrosis
accustomed to dealing with these issues. This blind spot is factor alpha, neutrophil count, D-dimer, plasminogen acti-
increasingly being addressed at the educational level within vator inhibitor-1, testosterone, insulin-like growth factor-1,
cardiology curricula and continuing medical education albumin, vitamin D, lymphocyte count, and memory/naive
programs. CD8 T-cell ratio. Thus, efforts to develop a specific
760 Afilalo et al. JACC Vol. 63, No. 8, 2014
Frailty in Cardiovascular Care March 4, 2014:747–62

biomarker or panel of biomarkers for frailty have been un-

Reprint requests and correspondence: Dr. Jonathan Afilalo,
successful to date (90). Divisions of Cardiology and Clinical Epidemiology, Jewish Gen-
With the accrual of diagnostic and prognostic data in eral Hospital, McGill University, 3755 Cote Sainte Catherine
CVD cohorts, we are now on the horizon of therapeutic Road, E-222, Montreal, Quebec H3T 1E2, Canada. E-mail:
trials to define how to best care for our frail cardiac patients jonathan.afilalo@mcgill.ca.
(91,92). Interventions may be divided into those that:
1) direct frail patients toward less invasive therapeutic REFERENCES
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J Nutr Health Aging 2011;15:834–46. Key Words: cardiovascular disease - elderly - frailty.