Delirium Incidence and Functional Outcomes After Transcatheter and Surgical Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) may be associated with less delirium and allow faster recovery than surgical aortic valve replacement (SAVR). OBJECTIVE: To examine the association of delirium and its severity with clinical and functional outcomes after SAVR and TAVR. DESIGN: Prospective cohort study. SETTING: An academic medical center. PARTICIPANTS: A total of 187 patients, aged 70 years and older, undergoing SAVR (N = 77) and TAVR (N = 110) in 2014 to 2016. MEASUREMENTS: Delirium was assessed daily using the Confusion Assessment Method (CAM), with severity measured by the CAM-Severity (CAM-S) score (range = 0-19). Outcomes were prolonged hospitalization (9 days or more); institutional discharge; and functional status, measured by ability to perform 22 daily activities and physical tasks over 12 months. RESULTS: SAVR patients had a higher incidence of delirium than TAVR patients (50.7% vs 25.5%; P < .001), despite younger mean age (77.9 vs 83.7 years) and higher baseline Mini-Mental State Examination score (26.9 vs 24.7). SAVR patients with delirium had a shorter duration (2.2 vs 3.4 days; P = .04) with a lower mean CAM-S score (4.5 vs 5.7; P = .01) than TAVR patients with delirium. The risk of prolonged hospitalization in no, mild, and severe delirium was 18.4%, 30.8%, and 61.5% after SAVR (P for trend = .009) and 26.8%, 38.5%, and 73.3% after TAVR (P for trend = .001), respectively. The risk of institutional discharge was 42.1%, 58.3%, and 84.6% after SAVR (P for trend = .01) and 32.5%, 69.2%, and 80.0% after TAVR (P for trend <.001), respectively. Severe delirium was associated with delayed functional recovery after SAVR and persistent functional impairment after TAVR at 12 months. CONCLUSION: Less invasive TAVR was associated with lower incidence of delirium than SAVR. Once delirium developed, TAVR patients had more severe delirium and worse functional status trajectory than SAVR patients did. REGISTRATION: NCT01845207.

Frailty in Older Adults Undergoing Aortic Valve Replacement: The FRAILTY-AVR Study.

BACKGROUND: Frailty is a geriatric syndrome that diminishes the potential for functional recovery after a transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) procedure; however, its integration in clinical practice has been limited by a lack of consensus on how to measure it. OBJECTIVES: This study sought to compare the incremental predictive value of 7 different frailty scales to predict poor outcomes following TAVR or SAVR. METHODS: A prospective cohort of older adults undergoing TAVR or SAVR was assembled at 14 centers in 3 countries from 2012 to 2016. The following frailty scales were compared: Fried, Fried+, Rockwood, Short Physical Performance Battery, Bern, Columbia, and the Essential Frailty Toolset (EFT). Outcomes of interest were all-cause mortality and disability 1 year after the procedure. RESULTS: The cohort was composed of 1,020 patients with a median age of 82 years. Depending on the scale used, the prevalence of frailty ranged from 26% to 68%. Frailty as measured by the EFT was the strongest predictor of death at 1 year (adjusted odds ratio [OR]: 3.72; 95% confidence interval [CI]: 2.54 to 5.45) with a C-statistic improvement of 0.071 (p < 0.001) and integrated discrimination improvement of 0.067 (p < 0.001). Moreover, the EFT was the strongest predictor of worsening disability at 1 year (adjusted OR: 2.13; 95% CI: 1.57 to 2.87) and death at 30 days (adjusted OR: 3.29; 95% CI: 1.73 to 6.26). CONCLUSIONS: Frailty is a risk factor for death and disability following TAVR and SAVR. A brief 4-item scale encompassing lower-extremity weakness, cognitive impairment, anemia, and hypoalbuminemia outperformed other frailty scales and is recommended for use in this setting. (Frailty Assessment Before Cardiac Surgery & Transcatheter Interventions; NCT01845207).

Evaluation of algorithms to identify delirium in administrative claims and drug utilization database.

PURPOSE: To evaluate the performance of delirium-identification algorithms in administrative claims and drug utilization data. METHODS: We used data from a prospective study of 184 older adults who underwent aortic valve replacement at a single academic medical center to evaluate the following delirium-identification algorithms: (1) International Classification of Diseases (ICD) diagnosis codes for delirium; (2) antipsychotics use; (3) either ICD diagnosis codes or antipsychotics use; and (4) both ICD diagnosis codes and antipsychotics use. These algorithms were evaluated against a validated bedside assessment, the Confusion Assessment Method, and a validated delirium severity scale, the CAM-S. RESULTS: Delirium occurred in 66 patients (36%), of which 14 (21%) had hyperactive or mixed features and 15 (23%) had severe delirium. ICD diagnosis codes for delirium were present in 15 patients (8%). Antipsychotics were used in 13 patients (7%). ICD diagnosis codes alone and antipsychotics use alone had comparable sensitivity (18% vs. 18%) and specificity (98% vs. 99%). Defining delirium using either ICD diagnosis codes or antipsychotics use, sensitivity improved to 30% with little change in specificity (97%). This algorithm showed higher sensitivity for hyperactive or mixed delirium (64%) and severe delirium (73%). Requiring both ICD diagnosis codes and antipsychotics use resulted in perfect specificity but low sensitivity (6%). CONCLUSION: Delirium-identification algorithms in claims data have low sensitivity and high specificity. Defining delirium using ICD diagnosis codes or antipsychotics use performs better than considering either type of information alone. This information should inform the design and interpretation of claims-based comparative effectiveness and safety research. Copyright © 2017 John Wiley & Sons, Ltd.

Preoperative Frailty Assessment and Outcomes at 6 Months or Later in Older Adults Undergoing Cardiac Surgical Procedures: A Systematic Review.

BACKGROUND: Frailty assessment may inform surgical risk and prognosis not captured by conventional surgical risk scores. PURPOSE: To evaluate the evidence for various frailty instruments used to predict mortality, functional status, or major adverse cardiovascular and cerebrovascular events (MACCEs) in older adults undergoing cardiac surgical procedures. DATA SOURCES: MEDLINE and EMBASE (without language restrictions), from their inception to 2 May 2016. STUDY SELECTION: Cohort studies evaluating the association between frailty and mortality or functional status at 6 months or later in patients aged 60 years or older undergoing major or minimally invasive cardiac surgical procedures. DATA EXTRACTION: 2 reviewers independently extracted study data and assessed study quality. DATA SYNTHESIS: Mobility, disability, and nutrition were frequently assessed domains of frailty in both types of procedures. In patients undergoing major procedures (n = 18 388; 8 studies), 9 frailty instruments were evaluated. There was moderate-quality evidence to assess mobility or disability and very-low- to low-quality evidence for using a multicomponent instrument to predict mortality or MACCEs. No studies examined functional status. In patients undergoing minimally invasive procedures (n = 5177; 17 studies), 13 frailty instruments were evaluated. There was moderate- to high-quality evidence for assessing mobility to predict mortality or functional status. Several multicomponent instruments predicted mortality, functional status, or MACCEs, but the quality of evidence was low to moderate. Multicomponent instruments that measure different frailty domains seemed to outperform single-component ones. LIMITATION: Heterogeneity of frailty assessment, limited generalizability of multicomponent frailty instruments, few validated frailty instruments, and potential publication bias. CONCLUSION: Frailty status, assessed by mobility, disability, and nutritional status, may predict mortality at 6 months or later after major cardiac surgical procedures and functional decline after minimally invasive cardiac surgery. PRIMARY FUNDING SOURCE: National Institute on Aging and National Heart, Lung, and Blood Institute.

Statins Provide Less Benefit in Populations with High Noncardiovascular Mortality Risk: Meta-Regression of Randomized Controlled Trials.

OBJECTIVES: To examine whether the benefit of statins varied according to cardiovascular (CV) and non-CV mortality of the treated population. DESIGN: Meta-analysis and meta-regression of 16 randomized placebo-controlled trials. SETTING: Community and hospital. PARTICIPANTS: Statin- (n = 59,671) and placebo-treated (n = 59,707) individuals with and without CV disease (mean age 55 to 75). MEASUREMENTS: Meta-regression was used to model relative risks (RRs) of major CV events (myocardial infarction and stroke) and total mortality for statins versus placebo as a function of CV and non-CV mortality risks of the study population. RESULTS: Every 1% increase in 5-year non-CV mortality risk of the study population was associated with a 3.7% (95% confidence interval (CI) = 1.2 to 6.3%) greater RR of major CV events and a 4.4% (95% CI = 2.1 to 6.9%) greater RR of total mortality. (Higher RRs indicate smaller benefits.) CV mortality was not associated with statin effects (P > .05). In stratified analysis according to CV (≥5.3% vs <5.3%) and non-CV mortality (≥3.8% vs <3.8%) of the study population, statins had little mortality benefit in populations with high non-CV mortality, regardless of CV mortality (random-effects pooled RR = 0.81, 95% CI = 0.72 to 0.91, for low CV and low non-CV mortality; random-effects pooled RR = 0.90, 95% CI = 0.76 to 1.06 for low CV and high non-CV mortality; random-effects pooled RR = 0.79, 95% CI = 0.72 to 0.87 for high CV and low non-CV mortality; random-effects pooled RR = 0.94, 95% CI = 0.87 to 1.02 for high CV and high non-CV mortality). The CV event reduction was also attenuated in populations with high non-CV mortality (random-effects pooled RR = 0.67, 95% CI = 0.60 to 0.75, for low CV and low non-CV mortality; random-effects pooled RR = 0.73, 95% CI = 0.66 to 0.81 for low CV and high non-CV mortality; random-effects pooled RR = 0.77, 95% CI = 0.69 to 0.87 for high CV and low non-CV mortality; random-effects pooled RR = 0.83, 95% CI = 0.74 to 0.92 for high CV and high non-CV mortality). CONCLUSION: Benefits of statins may depend on the non-CV mortality risk of the treated population. This should be confirmed using individual-level data.

Bisphosphonates and risk of cardiovascular events: a meta-analysis.

BACKGROUND AND OBJECTIVES: Some evidence suggests that bisphosphonates may reduce atherosclerosis, while concerns have been raised about atrial fibrillation. We conducted a meta-analysis to determine the effects of bisphosphonates on total adverse cardiovascular (CV) events, atrial fibrillation, myocardial infarction (MI), stroke, and CV death in adults with or at risk for low bone mass. METHODS: A systematic search of MEDLINE and EMBASE through July 2014 identified 58 randomized controlled trials with longer than 6 months in duration that reported CV events. Absolute risks and the Mantel-Haenszel fixed-effects odds ratios (ORs) and 95% confidence intervals (CIs) of total CV events, atrial fibrillation, MI, stroke, and CV death were estimated. Subgroup analyses by follow-up duration, population characteristics, bisphosphonate types, and route were performed. RESULTS: Absolute risks over 25-36 months in bisphosphonate-treated versus control patients were 6.5% versus 6.2% for total CV events; 1.4% versus 1.5% for atrial fibrillation; 1.0% versus 1.2% for MI; 1.6% versus 1.9% for stroke; and 1.5% versus 1.4% for CV death. Bisphosphonate treatment up to 36 months did not have any significant effects on total CV events (14 trials; ORs [95% CI]: 0.98 [0.84-1.14]; I2 = 0.0%), atrial fibrillation (41 trials; 1.08 [0.92-1.25]; I2 = 0.0%), MI (10 trials; 0.96 [0.69-1.34]; I2 = 0.0%), stroke (10 trials; 0.99 [0.82-1.19]; I2 = 5.8%), and CV death (14 trials; 0.88 [0.72-1.07]; I2 = 0.0%) with little between-study heterogeneity. The risk of atrial fibrillation appears to be modestly elevated for zoledronic acid (6 trials; 1.24 [0.96-1.61]; I2 = 0.0%), not for oral bisphosphonates (26 trials; 1.02 [0.83-1.24]; I2 = 0.0%). The CV effects did not vary by subgroups or study quality. CONCLUSIONS: Bisphosphonates do not have beneficial or harmful effects on atherosclerotic CV events, but zoledronic acid may modestly increase the risk of atrial fibrillation. Given the large reduction in fractures with bisphosphonates, changes in osteoporosis treatment decision due to CV risk are not justified.

Functional status and quality of life after transcatheter aortic valve replacement: a systematic review.

BACKGROUND: The functional and quality-of-life benefits of transcatheter aortic valve replacement (TAVR) have not been established. PURPOSE: To evaluate the changes in functional status and quality of life after TAVR. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1 January 2002 to 30 September 2013. STUDY SELECTION: Studies of TAVR that reported the New York Heart Association (NYHA) class, Short Form-12/36 Health Survey physical and mental component summary (points), or other measures of functional status. DATA EXTRACTION: Two reviewers independently extracted the mean change (follow-up minus baseline) in primary outcomes. Because of substantial heterogeneity, data were not pooled; the range of mean change was summarized. DATA SYNTHESIS: We identified 60 observational studies (56 pre­post comparison and 4 head-to-head comparative studies) and 2 randomized, controlled trials (11 205 patients). Most studies showed a clinically important decrease in NYHA class at 6 to 11 months (range, -0.8 to -2.1 classes) and 12 to 23 months (range, -0.8 to -2.1 classes). The improvement in the Short Form-12/36 Health Survey physical component score was clinically important over 12 months (range, 4.9 to 26.9 points), and the change in mental component score was smaller (range, 1.0 to 8.9 points).Clinically important improvements were seen in other disease-specific measures but were less consistently seen in general health measures. LIMITATIONS: Comparative evidence is limited by few head-to-head studies. Survivor bias may have overestimated the benefits. CONCLUSION: Transcatheter aortic valve replacement provides clinically important benefits in physical function and disease-specific measures of quality of life but modest benefits in psychological and general health measures. More comparative studies on functional status and quality of life are needed for informed treatment decision making.

Does age bias the aggressive treatment of elderly patients with rheumatoid arthritis?

OBJECTIVE: Age bias has been reported to result in undertreatment of elderly patients with various medical conditions. We investigated whether a similar bias exists in the treatment of elderly patients with rheumatoid arthritis (ELDRA) compared to matched younger controls (YRA). METHODS: We performed an analysis of our RA clinical research registry to determine whether any differences exist between ELDRA and YRA patients with respect to use of combination disease modifying antirheumatic drugs (DMARD), biologic agents, corticosteroids, and nonsteroidal antiinflammatory drugs (NSAID). We also determined whether any difference in clinical status could be identified. RESULTS: Forty-nine female ELDRA subjects (age > 70 yrs) with insurance were matched for sex, insurance status, and duration of disease to YRA subjects (< 60 yrs). No statistically significant difference was noted in number of DMARD currently in use (1.24 +/- 0.78 vs 1.24 +/- 0.69, p = 1.00), or number of patients using biologic agents (25 vs 30; p = 0.31), corticosteroids (16 vs 11; p = 0.26), or NSAID (26 vs 36; p = 0.06). ELDRA and YRA patients also reported similar pain (judged using a visual analog scale, VAS; 3.5 +/- 2.6 cm vs 3.4 +/- 2.2 cm), fatigue (VAS 3.2 +/- 2.7 cm vs 3.9 +/- 2.9 cm), global assessment (VAS 2.8 +/- 2.2 cm vs 3.5 +/- 2.6 cm), and Health Assessment Questionnaire disability scores (0.82 +/- 0.5 vs 0.73 +/- 0.5). CONCLUSION: In this cohort of elderly patients with RA, we detected no bias in the use of RA treatment compared with younger controls. Clinical RA measures also showed that these elderly patients with RA were faring at least as well as the younger controls; they were not relatively undertreated.