Frailty and pre-frailty in cardiac surgery: a systematic review and meta-analysis of 66,448 patients

Abstract

Background: The burden of frailty on cardiac surgical outcomes is incompletely understood. Here we perform a systematic review and meta-analysis of studies comparing frail versus pre-frail versus non-frail patients following cardiac surgery.

Methods: We searched MEDLINE and EMBASE databases until July 2018 for studies comparing cardiac surgery outcomes in "frail", "pre-frail" and "non-frail" patients. Data was extracted in duplicate. Primary outcome was operative mortality.

Results: There were 19 observational studies with 66,448 patients. Frail patients were more likely female (risk ratio [RR]1.7; 95%CI:1.5-1.9), older (mean difference: 2.4; 95%CI:1.3-3.5 years older) with greater comorbidities and higher STS-PROM. Frailty (RR2.35; 95%CI:1.57-3.51; p < 0.0001) and pre-frailty (RR2.03; 95%CI:1.52-2.70; p < 0.00001) were associated with increased operative mortality compared with non-frail patients. Frailty was also associated with greater risk of prolonged hospital stay (RR1.83; 95%CI:1.61-2.08; p < 0.0001) and intermediate care facility discharge (RR2.71; 95%CI:1.45-5.05; p = 0.002). Frail (Hazard Ratio [HR]3.27; 95%CI:1.93-5.55; p < 0.0001) and pre-frail patients (HR2.30; 95%CI:1.29-4.09; p = 0.005) had worse mid-term mortality (median follow-up 1 years [range 0.5-4 years]). After adjustment for baseline imbalances, frailty was still associated with greater operative mortality (odds ratio [OR]1.97; 95%CI:1.51-2.57; p < 0.00001), intermediate care facility discharge (OR4.61; 95%CI:2.78-7.66; p < 0.00001) and midterm mortality (HR1.37; 95%CI:1.03-1.83; p = 0.03).

Conclusion: In patients undergoing cardiac surgery, frailty and pre-frailty were associated with 2-fold and 1.5-fold greater adjusted operative mortality, respectively, greater adjusted perioperative complications and frailty was associated with almost 5-fold risk of non-home discharge. Burden of frailty and pre-frailty on cardiac surgical outcomes.

Keywords: Coronary artery bypass graft; Frailty; Valve surgery.

Fig. 1

Forest Plot for unadjusted operative mortality. Individual study and pooled unadjusted risk ratios (RRs) of frail vs non-frail patients undergoing primarily CABG and valve surgery. The pooled RR and OR with 95% CI were calculated using random-effects models. Esses et al. [22] provided (unadjusted) results using three different frailty indices: modified frailty index (mFI), Ganapathi index, and risk analysis index (RAI). All three results are shown in the unadjusted figure but only the RAI results were used to calculate the pooled results in the figure. The pooled results are similar if the modified frailty index (RR 2.38, 95% CI 1.57 to 3.62, p < 0.0001; I² = 72%) or Ganapathi index (RR2.28, 95%CI:1.56–3.35, p < 0.0001; I² = 69%) are used. Sensitivity analyses – Unadjusted risk of operative mortality also higher if the two studies with largest weighting ([14, 24]) are excluded: RR2.99, 95%CI:2.34–3.82, p < 0.00001, I² = 0% (the unadjusted risk of operative mortality remains higher if the next two largest weightings are also excluded ([6, 22]): RR1.85, 95%CI:1.02–3.34, p = 0.04, I² = 0%)

Fig. 2

Forest Plot for adjusted operative mortality. Individual study and pooled adjusted odds ratios (ORs) of frail vs non-frail patients undergoing primarily CABG and valve surgery. The pooled RR and OR with 95% CI were calculated using random-effects models. Sensitivity analyses – Adjusted risk of operative mortality is also higher if study with largest weighting [14] is excluded: adjusted OR 1.72, 95% CI 1.08–2.75, p = 0.02, I² = 0%

Fig. 3

Forest Plot for perioperative complications. Individual study and pooled unadjusted risk ratios (RRs) of frail vs non-frail patients undergoing primarily CABG and valve surgery. The pooled RRs with 95% CI were calculated using random-effects models. Sensitivity Analyses – Removing the results of the study with largest weighting [14] made the pooled results for reoperation [90% weighting, RR1.57, 95%CI:0.90–2.71, p = 0.11, I² = 0%] and deep sternal wound infection [56% weighting, RR1.29, 95%CI:0.52–3.17, p = 0.58, I² = 0%] no longer statistically significant, but the results for prolonged ventilation [57% weighting, RR1.96, 95%CI:1.63–2.36, p < 0.00001, I² = 5%] and acute kidney injury [51% weighting, RR2.40, 95%CI:1.83–3.15, p < 0.00001, I² = 0%] remained statistically significantly higher

Fig. 4

Forest Plot for prolonged hospitalization (Top) and discharge to an intermediate care facility (Bottom). Individual study and pooled unadjusted risk ratios (RRs) of frail vs non-frail patients undergoing primarily CABG and valve surgery. The pooled RRs with 95% CI were calculated using random-effects models. Sensitivity Analyses – Risk of prolonged hospital stay also higher if study with largest weighting is excluded [6]: RR1.69, 95%CI:1.34–2.13, p < 0.0001, I² = 0%. Adjusted risk of discharge to intermediate care facility is also higher if study with largest weighting is excluded [6]: adj OR 3.16, 95%CI:1.66–6.02, p = 0.0005, I² = 0%

Fig. 5

Forest Plot for adjusted discharge to an intermediate care facility. Individual study and pooled adjusted odds ratios (ORs) of frail vs non-frail patients undergoing primarily CABG and valve surgery. The pooled ORs with 95% CI were calculated using random-effects models. Sensitivity Analyses – Adjusted risk of discharge to intermediate care facility is also higher if study with largest weighting [6] is excluded: adjusted OR 3.16, 95% CI 1.66–6.02, p = 0.0005, I² = 0%

Fig. 6

Forest Plot for mid-term mortality. Individual study and pooled unadjusted (Top) and adjusted (Bottom) hazard ratios (HRs) of frail vs non-frail patients undergoing primarily CABG and valve surgery. The pooled HRs with 95% CI were calculated using random-effects models. Afilalo et al. [21] provided two separate adjusted results; the adjusted results using the Society of Thoracic Predicted Risk of Mortality (STS PROM) were used to calculate the pooled adjusted results in the figure. If the other adjusted results using comorbidities were used (also shown in the figure) the pooled adjusted results were similar: HR1.41, 95%CI:1.02–1.96, p = 0.04; I² = 71%. Sensitivity analyses – Risk of unadjusted long-term mortality remains higher if study with largest weighting is excluded [24]: HR3.85, 95%CI:2.63–5.64, p < 0.00001, I² = 5%) but adjusted mid-term mortality was no longer statistically significant if study with largest weighting is excluded [24]: HR1.65, 95%CI:0.95–2.85, p = 0.07, I² = 71%