Table 1.

Characteristics of reviewed studies on frailty and VHD.

Publication  (year)	Sample size (N) Patient population (Age, Female N (%))	Intervention Frail sample N (%)	Tool for frailty assessment	Primary end point	Main results/Conclusions
Abramowitz (2016) [29]	N=805; Age 82.0±8.8, F 321 (39,9%)	TAVI 279 (34.7%)	(1) MFFC (2) BMI	(1) To assess the influence of BMI on the short- and midterm clinical outcome following TAVI.	(1) Obese patients had lower prevalence of frailty. (2) All-cause mortality up to 30 days was 2.9% (10/340) vs 4.5% (12/268) vs 0.5% (1/186) in patients with normal weight, overweight, and obesity, respectively (p<0.048). (3) In a multivariable model, overweight and obese patients had similar overall mortality compared to patients with normal weight.
Ad   (2016) [33]	N=167; Age 74.1±6.6, F 41 (25%)	Cardiac surgery 39 (23%)	(1) FFS	(1) Impact of frailty on outcomes of patients undergoing cardiac surgery	(1) Frail patients had longer median ICU stays (54 vs. 28h, p=0.003), longer median LOS (8 vs. 5 days, p<0.001), greater likelihood of STS-defined complications (54% vs. 32%, p=0.011), and discharge to an intermediate-care facility (45% vs. 12%, p<0.001) (2) not different from non-frail patients on major outcome, operative mortality, or readmissions.
Afilalo   (2010) [6]	N=131; Age 75.8± 4.4; F 44 (34%)	Open cardiac surgery 60 (46%)	(1) 5MWT	(1) Inhospital post-operative mortality or major morbidity, defined by the STS.	(1) Slow gait speed was an independent predictor of the composite end point after adjusting for the STS risk score (OR: 3.05; 95% CI: 1.23 to 7.54).
Afilalo  (2012) [12]	N=152; Age 75,9±4,4, F 52 (34%)	Cardiac surgery 20%- 46%	(1) FFS (2) 7-item FFS (3) 4-item MSSA (4) 5MWT	(1) The STS composite end point of in-hospital postoperative mortality or major morbidity	(1) The most predictive scale in each domain was 5MWT (2) ≥6 s as a measure of frailty
Afilalo   (2016) [52]	N=15171; Age 71, F 4622 (30.5%).	Cardiac surgery 4588 (30,24%)	(1) 5MWT	(1) Operative mortality or within 30 d	(1) Compared with patients in the fastest gait speed tertile, operative mortality was increased for those in the middle tertile (0.83-1.00m/s; OR, 1.77; 95% CI, 1.34-2.34) and slowest tertile. (2) After adjusting gait speed remained independently predictive of operative mortality (OR, 1.11 per 0.1-m/s decrease in gait speed; 95% CI, 1.07-1.16). (3) Gait speed was also predictive of the composite outcome of mortality or major morbidity (OR, 1.03 per 0.1-m/s decrease in gait speed; 95% CI, 1.00-1.05).
Afilalo  (2017) [24]	N=1020; Age 82 (77–86), F 421 (41%)	SAVR, TAVI 26-68%	(1) FFS (2) MFFC (3) CHSA (4) SPPB (5) Bern scale (6) Columbia scale (7) EFT	(1)Death from any cause at 12 mo (2) death from any cause at 30 d or worsening and institutionalization (3) new accrued disabilities at 12 mo	(1) EFT was the strongest predictor of death at 1 y (adjusted [OR]: 3.72; 95% [CI]: 2.54 to 5.45). (2) EFT was the strongest predictor of worsening disability at 1 y (adjusted OR: 2.13; 95% CI: 1.57 to 2.87) and death at 30 d (adjusted OR: 3.29; 95% CI: 1.73 to 6.26).
Alfredsson   (2016) [51]	N=8039; Age 84 (79–88) F 4128 (51.4%)	TAVI 6100 (75,88%)	(1) 5MWT	(1) all-cause mortality at 30 d	(1) 30-d all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively (P<0.001). (2) Each 0.2-m/s decrease corresponded to an 11% increase in 30-d mortality (adjusted OR, 1.11; 95% CI, 1.01–1.22). (3) The slowest walkers had 35% higher 30-d mortality than normal walkers (adjusted OR, 1.35; 95% CI, 1.01–1.80), significantly longer LOS, and a lower probability of being discharged to home.
Arnold   (2017) [32]	N=2830; Age 83.3, F 1284 (45.4%)	TAVI 1692 (59.8%)	(1) FFS	(1) death within the first 6 mo after TAVI; (2) very poor QoL at 6 mo; (3) moderate worsening in QoL from baseline to 6 mo	(1) For all models except the 1-year clinical model, frailty was associated with an increase in the odds of a poor outcome of 30% to 40% when added to the existing models; (2) Adding frailty as a syndrome increased the c-indexes by 0.000 to 0.004, with the most important individual components being disability and unintentional weight loss
Assmann  (2016) [19]	N=89; Age 80.4±6,3, F 51 (57%)	TAVI NA	(1) MGA/MGBE	(1) Postprocedural period, mortality in 30 d follow-up	(1) Variables from frailty assessment protectively associated with delirium were MMSE, IADL and gait speed (2) TUG was predictively associated with delirium (3) MMSE was independently associated with delirium. (4) Variables predictively associated with mortality were the summary score Frailty Index (HR 1.66, 95% CI 1.06 to 2.60; p=0.03) (5) Variables from frailty assessment are associated with delirium and mortality
Bagienski  (2017) [20]	N=141; Age 82.0, F 89 (63,1%)	TAVI 2,8-90,1%	(1) 5MWT, (2) Elderly mobility scale (3) CSHA, (4 ) Katz index, (5) Grip strength, (6) ISAR	(1) All-cause mortality at 30 d and 12 mo	(1) 30-d and 12-mo all-cause mortality rates were higher in the delirium group (p <0.001). (2) Significantly more patients with delirium were considered as frail before TAVI.
Bogdan   (2016) [59]	N=150; Age 81±6 years F 90 (60%)	TAVI 79 (53%)	(1) Low albumin	(1) Correlation between baseline serum albumin and all-cause mortality in TAVI patients. (2) low post-procedural albumin following TAVI.	(1) Mortality was higher in the low albumin group compared with the normal albumin group (35% vs. 19%, p=0.01). (2) Multivariate analysis indicated that low preprocedural albumin (≤40 g/L) was independently associated with a more than twofold increase in 2.1 year all-cause mortality (p=0.01, HR=2.28; 95% CI: 1.174.44). (3) Low postprocedural serum albumin remained a strong parameter correlated with all-cause mortality (HR=2.47; 95% CI: 1.284.78; p<0.01).
Capodanno (2014) [63]	N=1878 NA F 1087 (57,9%)	TAVI 459 (24,4%)	(1) Geriatric status scale	(1) 30-d mortality	(1) Frailty OR 2.09, CI (1.30-3.37), p =0.003 (2) OBSERVANT risk model did not include frailty as a risk factor
Chauhan   (2016) [38]	N=342; Age 81.85, F 179 (52,3%)	TAVI 104 (30%)	(1) MFFC	(1) all-cause mortality (2) total postoperative LOS, discharge disposition and incidence of stroke.	(1) Patients with frailty score of 3/4 or 4/4 had increased all-cause mortality (P = 0.015 and P <0.001) and were more likely to be discharged to an ICU facility (P =0.083 and P = 0.001). (2) 4/4 frail patients had increased post-operative LOS (P = 0.014) (3) Individual components of the frailty score were also independent predictors of all-cause mortality. (4) The HR of mortality increased with each increase in frailty score
Cockburn  (2015) [64]	N=312; Age 81.2±6.8, F 146 (46,8%)	TAVI NA	(1) General mobility EuroSCORE II (2) Brighton mobility index (3) NYHA (4) Karnofsky performance scale (5) Katz Index (6) CSHA	(1) Assess whether different frailty indices predict outcomes both in the shorter and longer terms	(1) Both univariate and multivariate analyses confirmed poor mobility (EuroSCORE II), as the best predictor of adverse outcome over both the short-term (OR 4.03, 95% CI (1.36–11.96), P50.012 (30 days)) and longer term (OR 2.15, 95% CI (1.33–3.48), P50.002, (2.261.5 years.) (2) Mobility impairment, of either neurological or musculoskeletal etiology, is an appropriate screening measure when considering patients for TAVI.
Codner  (2015) [49]	N=360; Age 82. ± 6.9, F 203 (56.4%)	TAVI NA	(1) 5MWT (2) Katz Index, (3) albumin levels, (4) oxygen therapy, (5) cognitive status, (6) gen. appearance	All-cause mortality during follow-up.	In multivariate analysis frailty (HR 1.89, 95% CI 1.11 to 3.2, p =0.02) was independent predictor for all-cause mortality.
Dahya   (2016) [65]	N=104, Age 81 ± 10, F 50 (48%)	TAVI NA	CT scan – SMI MFFC	(1) Relationship between SMI and LOS	(1) A multivariate model showed SMI as independent predictors of LOS. (2) For every 14-cm2/m2 increase in SMI, there was a 1-d reduction in LOS. (3) None of the standard measures of frailty predicted LOS.
de Thézy  (2017) [66]	N=49; Age 84.8, F 27 (55.1%)	TAVI 41 (83.67%)	(1) G8 scale (2) CGA	(1) sensitivity and specificity of G8	(1) G8 had a sensibility of 100% (IC 95% [0.91]), a specificity of 72.7% (IC 95% [0.430.9]), a positive predictive value of 92.6% and a negative prospective value of 100% (IC: 95%). (2) G8 scale could be performed by cardiologists in older patients with AS for identifying patients with a geriatric risk profile in consultation before surgery.
Debonnaire (2015) [37]	N=511 Age 82 F 317 (62%)	TAVI 98 (21%)	(1) FFS (2) Eye ball test	(1) 1y mortality	(1) Frailty was not associated with the study end point
Eichler  (2017) [41]	N=344; Age 80.9 ± 5.0; F 191 (55,5%)	TAVI 152 (45.8%)	(1) MGA/MGBE	(1) All-cause mortality at 12 mo after TAVI.	(1) MGA/MGBE had no predictive power; its individual components, particularly nutrition (OR 0.83 per 1 pt., CI 0.72–0.95; p=0.006) and mobility (OR 5.12, CI 1.64–16.01; p=0.005) had a prognostic impact.
Esses  (2018) [43]	N= 3088; Age 69.24 ± 13.10, F 1163 (37.7)	SAVR 25,74- 56,19%	(1) modified CSHA (2) RAI (3) 6-mo mortality index by Porock (3) Ganapathi index	(1) 30-d mortality and major postoperative morbidity.	(1) Frailty was a better predictor of mortality than morbidity, and it was not markedly different among any of the 3 indices. (2) Frailty was associated with an increased risk of 30 d mortality and longer LOS.
Forcillo  (2017) [28]	N=361; Age 82; F 167 (43%)	TAVI NA	MFFC	(1) 30-d mortality and to compare the discrimination of 30-d mortality, and to compare its discriminative ability with STS PROM.	(1) For high- and extreme-risk patients undergoing TAVR, serum albumin, Katz Index, and 5MWT were associated with increased risk of adverse outcomes. (2) Only albumin was predictive of 30-day all-cause mortality.
Garg   (2017) [67]	N=152; Age 83.3±6.5, F 64 (42%)	TAVI 76 (50%)	(1) CT scan - PMA	(1) early poor outcome (30 d mortality, stroke, dialysis, and prolonged ventilation	(1) Indexed PMA ([OR] 3.19, [CI] 1.30 to 7.83; p =0.012) and age (OR 1.92, CI 1.87 to 1.98; p = 0.012) predicted early poor outcome. (2) High-resource utilization was observed more frequently in patients with PMA less than the median (73% vs 51%, OR 2.65, CI 1.32 to 5.36; p = 0.006).
Goldfarb   (2017) [31]	N=235 Age 73.0; F 68 (29%)	Cardiac surgery N=91, (38,72%)	FFS or SPPB	(1) The impact of preoperative frailty status on postoperative hospitalization costs	(1) The median cost was $32,742 in frail patients compared with $23,370 in non-frail patients (P < 0.001). (2) Total costs were independently associated with frailty and valve surgery (P < 0.001). (3) This effect persists after adjusting for age, sex, surgery type, and surgical risk score.
Green  (2013) [55]	N=484; Age 84,7, F 224 (46%)	TAVI 351 (72,52%)	(1) 6MWT	(1) association between baseline 6MWT and functional improvement (2) association between baseline 6MWT and mortality.	(1) There were no differences in 30-d outcomes among 6MWTD groups. (2) At 2 y, the rate of death from any cause was 42.5% in those unable to walk, 31.2% in slow walkers, and 28.8% in fast walkers (p = 0.02), driven primarily by differences in noncardiac death. (3) Patients with poor baseline functional status exhibit the greatest improvement in 6MWTD.
Green  (2015) [39]	N=244; Age 86,25, F 1118 (48,3%)	TAVI 110 (45%)	(1) MFFC	(1) Time to death from any cause over 1 y of follow up and poor outcome at 1y	(1) At 30 d, there were no differences in rates of MACCE according to baseline frailty status. (2) At 1 y all-cause mortality rate was 32.7% in the frail group and 15.9% in the non-frail group (log-rank p=0.004). (3) Frailty remained independently associated with an increased odds of poor outcome after TAVI at both 6 mo (OR 2.21, 95% CI 1.09–4.46, p = 0.03) and 1 y (OR 2.40, 95% CI 1.14–5.05, p = 0.02).
Grossman   (2017) [57]	N=426; Age 83.8, F 242 (56,8%)	TAVI 192 (45,07%)	(1) Low albumin	(2) 1-y all-cause mortality.	(1) Participants with low albumin levels had higher mortality (HR) = 3.03, 95% (CI) = 1.66–5.26, P < .001). (2) Participants with low serum albumin and a high STS (HR = 4.55, 95% CI = 2.21–9.38, P < .001) or EuroSCORE-2 (HR = 2.72, 95% CI = 1.48–5.06, P = .001) (3) Serum albumin, as a marker of frailty, can significantly improve the ability of STS and EuroSCORE-2 scores to predict TAVR-related mortality.
Herman  (2013) [68]	N=4270; Age 67, Female 25%	Cardiac surgery 171 (4%)	(1) Katz index (2) independence in ambulation (3) dementia	(1) Composite end point defined as MACCE	(1) Frailty was significant (OR 1.7; 95% CI 1.2-2.5) predictor. (2) The concordance statistic for the MACCE model in a mixed population was 0.764 (95% CL; 0.75-0.79) and had excellent calibration.
Hermiller  (2016) [69]	N=3687; Age 83.3 ± 7.8 F 1707 (46.3%)	TAVI NA	(1) 5MWT (2) grip strength (3) BMI (4) anemia (5) hypoalbuminemia (6) weight loss; (7) Fall	All-cause mortality rate 30 d and 1 y	(1) Albumin levels <3.3 g/dl predicted death at 30 d. (2) Albumin levels <3.3 g/dl, falls in the past 6 months, predicted death at 1 y. (3) This score (Albumin, assisted living, home oxygen, age>85y) showed a 3-fold difference in mortality rates for the low-risk and high-risk subsets at 30 d (3.6% and 10.9%, respectively) and 1 y (albumin, comorbidities, home oxygen, STS>7%) (12.3% and 36.6%, respectively).
Huded  (2016) [36]	N=191 Age 82.4 ± 9.2; F 93 (49%)	TAVI N=64, (33,5%)	FFS	(1) 30-d mortality, AE, hospital readmission (2) hospital LOS, (3) Discharge to a rehabilitation facility,	(1) There was no difference in 30-d mortality, major complications, mean hospital LOS, 30-day hospital re-admission, or overall survival between groups. (2) Frailty was independently associated with discharge to a rehabilitation facility (p=0.004).
Kamga  (2013) [70]	N=30; Age 86 ± 3, F 14 (47%)	TAVI NA	(1) The ISAR (2) The SHERPA score	(1) Outcomes 30 d and 1 y	(1) The ISAR score was similar but the SHERPA score was significantly higher in non-survivors (7.8 ±1.6 vs. 4.9 ±2.4; P = 0.001). (2) SHERPA score (>7) and BMI were independent predictors of 1y mortality (P = 0.004).
Kano   (2017) [50]	N=1256; Age NA F 895 (71,25%)	TAVI 693 (55,17%)	(1) 5MWT	(1) 30 d and 12 mo mortality	(1) The slowest walkers and those unable to walk demonstrated independent associations with increased midterm mortality after adjustment (HR, 1.83, 4.28; 95% CI, 1.03–3.26, 2.22–8.72; P=0.039, <0.001, respectively). (2) Gait speed <0.385 m/sec associated with worse prognosis (HR 2.40; 95% CI, 1.75–5.88; P=0.001). (3) Increased midterm mortality rate in patients with a gait speed of 0.385~0.5 m/sec, or unable to walk as compared with patients with a normal gait speed.
Kleczynski  (2017) [30]	N=101; Age 81.0 F 60.4%	TAVI 6,9-52,5%	(1) Katz index (2) EMS (3) Katz Index (4) CSH (5) 5MWT (6) Hand grip strength (7) ISAR	12-mo mortality	(1) Associations between frailty indices and 12-mo all-cause mortality were significant, adjusted for logistic EuroSCORE: (1) for 5MWT, 72.38 (15.95-328.44); (2) for EMS, 23.39 (6.89-79.34); (3) for CSHA scale, 53.97 (14.67-198.53); (4) for Katz index, 21.69 (6.89-68.25); (5) for hand grip strength, 51.54 (12.98-204.74); (6) for ISAR scale, 15.94 (2.10-120.74). (2) 5MWT, EMS, or hand grip test may be advocated.
Kobe   (2016) [71]	N=130; Age 83.3 F 65 (50%)	TAVI 71 (55%)	(1) FORECAST	(1) 12-mo mortality	(1) ROC showed that the FORECAST is a valid tool to predict in-hospital mortality (area 0.73). (2) By combining the FORECAST and the STS score, this effect was even higher (area 0.77; P = 0.021). (3) Stratifying the patients according to the FORECAST score showed best survival in the lowest frailty group.
Koifman   (2016) [62]	N=491; Age 83,8 F 245 (50%).	TAVI 43 (8,75%)	BMI	(1) all-cause mortality at 1 y of follow-up	(1) All-cause mortality at 1 y was higher in the low-BMI group (log-rank p=0.003) with no significant difference among normal and above-normal BMI patients. (2) In a multivariate model, BMI <20 kg/m2 was an independent predictor of mortality (HR=2.45, p=0.01)
Kotajarvi   (2017) [45]	N=103; Age 80.6 years, F 42 (40,1%)	SAVR 54 (52,4%)	(1) CSHA	(1) to determine the extent to which surgery affected measures of physical and mental health and QoL, (2) examine how changes in these patient-centered outcomes compared between non-frail and frail study participants.	(1) Frail participants had lower baseline independence and QoL measures; (2) At follow-up, frail participants showed significant improvement in physical function, with physical health scores improving by 50% and 14%. Non-frail subjects did not significantly improve in these measures. (3) Mental health scores also improved to a greater extent in frail participants (3.6 vs < 1 point). (4) Frail participants improved to a greater extent in physical well-being (21.6 vs 7.1 points) and quality of life measures (25.1 vs 8.7 points)
Laure Bureau (2017) [72]	N=116; Age 86.2 ± 4.2 F 116 (49.1%)	TAVI 10-58%	MPI score the sum of (1) Katz Index (2) MNA-SF (3) SPMSQ (4) CIRS	All cause of mortality at 1 mo	Mortality rate was significantly different between MPI groups at 6 and 12 mo (p=0.040 and p=0.022). Kaplan Meier survival estimates at 1 y stratified by MPI groups were significantly different (HR=2.83, 95% (CI) 1.38–5.82, p=0.004). Among variables retained to perform logistic regression analysis, Katz index appeared the most relevant (p < 0.001).
Lee  (2010) [15]	N=3826; Age 68,5; F 998 (26%)	Cardiac surgery 157 (4.1%)	(1) Katz index (2) independence in ambulation (3) dementia	(1) In-hospital mortality, midterm all-cause mortality and discharge to an institution	(1) Frailty was an independent predictor of in-hospital mortality (OR 1.8, 95% CI 1.1 to 3.0), as well as institutional discharge (OR 6.3, 95% CI 4.2 to 9.4). (2) Frailty was an independent predictor of reduced midterm survival (HR 1.5, 95% CI 1.1 to 2.2).
Mamane  (2016) [73]	N=208; Age 80.7± 6.8 F 114 (55%)	TAVI NA	(1) CT scan – PMA	All-cause mortality	(1) PMA was lower in non-survivors compared with survivors among women (12.9 vs 14.5 cm2; P = 0.047) but not men (21.7 vs 22.4 cm2; P = 0.50). (2) The association between PMA and all-cause mortality in women persisted after adjustment (HR, 0.88 per cm2; 95% CIerval, 0.78-0.99). (3) PMA is a marker of frailty associated with midterm survival in women
Martin  (2017) [74]	N=6339; Age, 81.3; F 2927 (46.2%)	TAVI NA	(1) Katz Index (2) CSHA (3) poor mobility	(1) Internally validate a multivariable TAVI CPM for predicting 30-d mortality in UK-TAVI patients	(1) The final UK-TAVI CPM included 15 risk factors, which included 2 variables associated with frailty. (2) Scale demonstrated strong calibration and moderate discrimination
Metze  (2017) [16]	N=213 Age 78 F 122 (42,7%)	PMVR 97 (45,5%)	(1) FFS	(1) procedural outcomes, short-term functional changes, and long-term clinical outcomes	(1) Mortality at 6 w was significantly higher in frail (8.3%) compared with nonfrail (1.7%) patients (p =0.03). Hazards of death (HR: 3.06; 95% CI: 1.54 to 6.07; p <0.001) and death or heart failure decompensation (HR 2.03; 95% CI 1.22 to 3.39; p. 0.007) were significantly increased in frail patients during long-term follow-up, which did not change relevantly after adjustment (2) PMVR can be performed with equal efficacy and is associated with at least similar short-term functional improvement in frail patients.
Mok   (2016) [61]	N=460; Age 81 ± 8 F 224 (49%)	TAVI Sarcopenia 293 (64%) Sarcopenic-Obesity 212 (46%)	(1) CT scan – SMM, FM	(1) assess the feasibility of evaluating body composition by CT (2) determine the prevalence of sarcopenia, obesity, sarcopenic obesity; (3) analyze the impact of differing body composition on 30-day and late clinical outcomes.	(1) Sarcopenia predicted cumulative mortality (HR 1.55, 95% confidence interval 1.02 to 2.36, p=0.04). (2) Differences in body composition had no impact on 30-day clinical outcomes after TAVI.
Nemec   (2017) [75]	N=238; Age 82.3 ± 10.0, F 78 (32,33%)	TAVI 53 (34%) sarcopenia,	(1) CT scan - SMI	(1) inter- and postprocedural complications (2) LOS, 30 d and 1-y mortality	(1) SMIs at L3 and T12 significantly correlated with prolonged LOS. (2) SMI3, SMI7 SMI12, SC, and BMI did not show a relationship with perioperative death or complications or 30- day and 1-year mortality rates. (3) VF showed a significant relationship with 30-day and 1-year mortality rates
Okoh   (2017) [34]	N=75; Age 92±2; F 49 (65%)	TAVI 30 (40%)	FFS	(1) all-cause mortality	(1) Significant improvement in overall health status of non-frail patients (mean difference: 11.03, P=0.032). (2) Unadjusted 30-day and 2-year mortality rates were higher in the frail group than the non-frail group (14% vs. 2% P = 0.059; 31% vs. 9% P = 0.018). (3) Kaplan-Meier estimated all-cause mortality to be significantly higher in the frail group (log-rank test; P = 0.042). (4) Frailty status was independently associated with increased mortality (hazard ratio: 1.84, 95% C.I: 1.06–3.17; P=0.028) after TAVI.
Paknikar   (2016) [76]	N=295; Age 74,68, F 102 (34,5%)	SAVR/TAVI NA	(1) CT scan - TPA	(1) To evaluate the use of sarcopenia as a frailty assessment tool	(1) 2 y survival was 85.7% in patients with sarcopenia, compared with 93.8% in patients without sarcopenia (P = .02). (2) Independent predictors of late survival included TPA (HR, 0.47; P = .02). (3) Male sex (OR, 0.52; P = .04) and TPA (OR, 0.6; P = .001) were predictive of high resource utilization. (4) A separate analysis by treatment group found that TPA predicted high resource utilization after SAVR (OR, 0.4; P<.001), but not after TAVI (P = .66)
Puls  (2014) [77]	N=300; Age 82±5 years F 198 (66%)	TAVI 144 (48%)	(1) Katz Index	(1) all-cause mortality	(1) Early mortality was significantly higher in frail persons (5.5% vs. 1.3%, p=0.04 for immediate procedural mortality; 17% vs. 5.8%, p=0.002 for 30-day mortality; and 23% vs. 6.4%, p<0.0001 for procedural mortality). (2) In contrast, the Katz Index <6 was identified as a significant independent predictor of long-term all-cause mortality by multivariate analysis (HR 2.67 [95% CI: 1.7-4.3], p<0.0001).
Rodés-Cabau   (2010) [78]	N=339; Age 81±8; F 187 (55,2%)	TAVI 85 (25.1)	Eye ball test	(1) Procedural and 30-d outcomes	(1) Patients with either porcelain aorta (18%) or frailty (25%) exhibited acute outcomes similar to the rest of the study population
Rodés-Cabau   (2012) [79]	N=339; Age 81±8; F 187 (55,2%)	TAVI; 85 (25.1)	Eye ball test	(1) the occurrence of mortality (yes/no)	(1) At a mean follow-up 188 patients (55.5%) had died. (2) The predictors of late mortality were frailty (HR: 1.52, 95% CI: 1.07 to 2.17).
Rodrigues   (2017) [46]	N=221; Age 71, F 76 (34,3%)	Cardiac surgery; Pre-frailty 144 (65,15%)	(1) CSHA	(1) main outcomes after cardiovascular surgery in pre-frail patients compared with non-frail patients.	(1) Pre-frail patients showed a longer mechanical ventilation time (193 ± 37 vs. 29 ± 7 hours; p<0.05), LOS at ICU (5 ± 1 vs. 3 ± 1 days; p < 0.05) and total time of hospitalization (12 ± 5 vs. 9 ± 3 days; p < 0.05). (2) In addition, the pre-frail group had a higher number of AE with an increased risk for development stroke (OR: 2.139, 95% CI: 0.622–7.351, p = 0.001; HR: 2.763, 95%CI: 1.206–6.331, p = 0.0001) and in-hospital death (OR: 1.809, 95% CI: 1.286–2.546, p = 0.001; HR: 1.830, 95% CI: 1.476–2.269, p = 0.0001). (3) higher number of pre-frail patients required homecare services (46.5% vs. 0%; p < 0.05).
Rodríguez-Pascual   (2016) [35]	N=606; Age 83,95, F 355 (58%)	TAVI/SAVR 299 (49.3%)	(1) FFS	(1) all-cause mortality during the follow-up	(1) The HR (95% CI) of mortality among frail versus non-frail patients was 1.83 (1.33–2.51). (2) frailty criteria were considered separately; mortality was also higher among patients with slow gait speed [1.52 (1.05–2.19)] or low physical activity [1.35 (1.00–1.85)].
Ryomoto   (2017) [80]	N=85; Age 78 ± 6, F 57 (67%)	AVR 8 (9,4%)	(1) FIM	(1) whether the preoperative FIM is useful for decision making for a strategy in the era of TAVI	(1) The preoperative motor FIM score was significantly lower in the compromised group (45 ± 24) than in the unaffected group (85 ± 9, p =<0.01). (2) The duration of postoperative intubation, ICU stay, and postoperative hospitalization were significantly longer in the compromised group than in the unaffected group (48 ± 67 vs 16 ± 12 h, p<0.01; 6.7 ± 5.3 vs 3.4 ± 2.0 days, p<0.01; 34 ± 27 vs 23 ± 11 days, p = 0.02, respectively).
Saji   (2016) [81]	N=232; Age 80.1 ± 8.7 F 132 (57%)	TAVR; 77 (33,2%)	(1) CT scan - PMA (2) 5MWT	(1) all-cause mortality at 30 d and 6 mo.	(1) After adjustment for multiple confounding factors, the normalized PMA tertile was independently associated with mortality at 6 mo (adjusted HR 1.53, 95%, CI 1.06 to 2.21). (2) Kaplan-Meier analysis showed that tertile 3 had higher mortality rates than tertile 1 at 6 m (14% and 31%, respectively, p =0.029). (3) PMA is an independent predictor of mortality after TAVI; 5MWT combined with normalized PMA showed greater discrimination ability than alone.
Saji   (2017) [27]	N=155; Age 85 F 99 (65)	TAVI NA	(1) SPPB (2) MFFC (3) PARTNER scale (4) Frailty index (Japan) (5) CSHA (6) 5MWT	(1) all-cause unplanned readmission following TAVI	(1) Frailty markers other than MFFC were independently associated with unplanned readmission. (2) The analysis found that the SPPB, the PARTNER frailty scale, the frailty index, CSHA and 5MWT were independently associated with unplanned readmission even after adjustment in the multivariate analysis.
Schoenenberger (2013) [17]	N=119; Age 83.4+4.6 years; F 66 (55.5%)	TAVI   59 (49.6%)	(1) MGA/MGBE	(1) Functional decline over 6 mo	(1) 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). (2) Overall predictive performance was best for the frailty index [Nagelkerke's R2 (NR2) 0.135] and low for the EuroSCORE (NR2 0.015) and STS score (NR2 0.034). (3) In univariable analyses, all components of the frailty index contributed to the prediction of functional decline.
Seiffert  (2014) [44]	N=845; Age 80.9 ± 6.5 F 432 (51.1%)	TAVI 16 (4.6)	(1) CSHA	(1) to determine the additional value of indicators of frailty for postoperative survival in the elderly patient sample in the last step	(1) BMI, eGFR, hemoglobin, pulmonary hypertension, mean transvalvular gradient and LV ejection fraction at baseline were most strongly associated with mortality and entered the risk prediction algorithm [C -statistic 0.66, 95 % confidence interval (CI) 0.61–0.70, calibration v2 -statistic = 6.51; P = 0.69]. (2) Frailty increased the C -statistic to 0.71, 95 % CI 0.65–0.76. (3) Frailty was strongly related to outcome and increased the discriminatory ability of the risk algorithm.
Shimura  (2017) [47]	N=1215; Age 84.4 ± 5.0, F 854 (70,2%)	TAVI Moderately frail 122 (10.0%) Severely frail 48 (4.0%)	(1) CSHA (2) BMI (3) Albumin, (4) 5MWT (5) Hand grip.	The 30-d mortality and in-hospital mortality	(1) Cumulative 1-y mortality increased with increasing CSHA stage (7.2%, 8.6%. 15.7%, 16.9%, 44.1%, p<0.001). (2) In a Cox regression multivariate analysis, the CSHA (per 1 category increase) was an independent predictive factor of increased late cumulative mortality risk (HR: 1.28; 95% CI: 1.10-1.49; p<0.001).
Stortecky   (2012) [14]	N=100; Age 83.7± 4.6 F 60 (60.0%)	TAVI 49 (49.0%)	(1) MGA/MGBE	(1) outcomes at 30 day and 1 year	(1) Associations of cognitive impairment (odds ratio [OR]: 2.98, 95% confidence interval [CI]: 1.07 to 8.31), malnutrition (OR: 6.72, 95% CI: 2.04 to 22.17), mobility impairment (OR: 6.65, 95% CI: 2.15 to 20.52), limitations in basic ADL (OR: 3.63, 95% CI: 1.29 to 10.23), and frailty index (OR: 3.68, 95% CI: 1.21 to 11.19) with 1-year mortality were similar compared with STS score (OR: 5.47, 95% CI: 1.48 to 20.22) and EuroSCORE (OR: 4.02, 95% CI: 0.86 to 18.70). (2) Similar results were found for 30-day mortality and MACCE.
Sunderman (2011) [82]	N=400 Age 80.3 ±4 F 206 (51,5%)	Cardiac surgery Moderately frail 170 Severely frail 31	(1) CAF	(1) correlation of Frailty score to 30-d mortality.	(1) There were low-to-moderate albeit significant correlations of Frailty score with STS score and EuroSCORE ( p < 0.05). (2) There was also a significant correlation between Frailty score and observed 30-day mortality ( p < 0.05). (3) The comprehensive assessment of frailty is an additional tool to evaluate elderly patients adequately before cardiac surgical interventions.
Sündermann   (2011) [11]	N=400; Age 80.1 ± 4 years, F 206 (51,5%)	Cardiac surgery 114 (55,33% )	CAF	(1) 1 y all-cause mortality	(1) Patients who died within 1 y had a median frailty score of 16 [5;33] compared to 11 [3;33] to the 1 y survivors (P = 0.001). (2) 1 y mortality within each CAF subgroup shows a significantly higher mortality rate among patients in the “severely frail” compared to less frail groups. (3) Higher frailty group had a LOS at the ICU. (4) The CAF score facilitates prediction of mid-term outcome of high-risk elderly patients
Yamamoto (2015) [58]	N=777; Age 83,9, F 400 (51,48%)	TAVI 56 (7,2%)	BMI	(1) The 30- d mortality	(1) Kaplan-Meier curves indicated no significant differences in cumulative 30-d and 1-y survival. (2) BMI <20 was not associated with increased early or midterm mortality.
Yamamoto (2017) [58]	N=1215; Age 84.4 ± 5.0, F 854 (70.3%)	TAVI 284, (23,3%)	(1) Low albumin	(1) all-cause mortality after TAVI	(1) cumulative all-cause, cardiovascular, and noncardiovascular mortality rates were significantly higher in the low albumin group than in the normal albumin group (log-rank test, p <0.001, p = 0.0021, and p <0.001, respectively). (2) Poorer prognosis of the low albumin group in terms of cumulative all-cause and non-cardiovascular mortality was retained (p = 0.038, and p = 0.0068, respectively)
Zuckerman (2017) [83]	N=82; Age 71,6 F 24, 29%	Cardiac surgery NA	(1) CT scan - PMA	(1) postoperative LOS defined as the number of days from index procedure to hospital discharge	(1) Low PMA was correlated with lower handgrip strength and SPPB scores indicative of physical frailty. (2) Postoperative LOS correlated with PMA (R=L0.47, p =0.004), LMA (R=–0.41, p=0.01), and TMA (R= –0.29, p=0.03). (3) After adjustment PMA remained significantly associated with LOS (β= –2.35, 95% CI –4.48 to –0.22). (4) The combination of low PMA and handgrip strength, indicative of sarcopenia, yielded the greatest incremental value in predicting LOS.

Intervention. TAVI: Transcatheter Aortic Valve Implantation, SAVR: survival aortic valve replacement, PMWR: percutaneous mitral valve repair.

Frailty Assessment. FFS: Fried phenotype frailty index, SPPB: Short Physical Performance Battery, 5MWT: 5-meter walking test, CSHA: Canadian Study of Health and Aging, ISAR: Identification of Seniors at Risk, MMSA: MacArthur Study of Successful Aging, EMS: Elderly Mobility Scale, EFT: Essential Frailty Toolset, MFFC: Modified Fried Frailty Criteria, BMI: body mass index, SHERPA: Score Hospitalier d'Evaluation du Risque de Perte d'Autonomie, CGA: comprehensive geriatric assessment, MPI: Multidimensional Prognostic Index, UK-TAVI CPM: UK TAVI clinical prediction models, RAI: risk analysis index, SMI: skeletal muscle index, 6MWT: six-minute walking test, CAF: comprehensive assessment of frailty, PMA: psoas muscle area, SMM: skeletal muscle mass, FM: fat mass, TPA: total psoas area, LMA: lumbar muscle area, TMA: thoracic muscle area, VF: visceral fat, SC: subcutaneous tissue area, FIM: functional independence measure, MGA/MGBE: Multidimensional Geriatric Assessment/Modified Geriatric Baseline examination, MMSE: Mini Mental State Examination, TUG: Time Up and Go, IDAL: instrumental activities in daily living, FORECAST: Frailty predicts death One yeaR after Elective CArdiac Surgery Test.

Outcomes. AE: Adverse events, LOS: length of stay, STS: Society of Thoracic Surgery, QoL: quality of life, NYHA: the New York Heart Association, MACCE: major adverse cardiac and cerebrovascular events.

Results. OR: odds ratio, HR: hazard ratio, CI: confidence interval, NA: not available, ICU: intensive care unit, eGFR: estimated glomerular filtration ratio.