Dietary protein intake in older adults undergoing cardiac surgery.

BACKGROUND: Older adults undergoing major surgery have increased protein requirements in the postoperative period, but there are limited data describing actual protein intake following cardiac surgery. METHODS AND RESULTS: We performed a prospective sub-study within a registry of older adults ≥60 years of age undergoing cardiac surgery at a tertiary care centre. A dietician administered a food frequency questionnaire before surgery and 1-4 months after surgery. In-hospital food intake was recorded by direct observation for 3 days in the early postoperative period. Food intake was analyzed to calculate the protein intake per kilogram of body weight per day (g/kg/d) during the three phases of care, compared to the dietary reference intake. Frailty was measured by a questionnaire and physical performance tests before surgery. There were 22 patients (8 females, 14 males; 59% frail) enrolled in the study with a mean age of 72.0 ± 7.8 years. The mean protein intake was 1.3 ± 0.5 g/kg/d, 0.7 ± 0.3 g/kg/d, and 1.3 ± 0.6 g/kg/d in the preoperative, early postoperative, and postdischarge periods, respectively (P < 0.0001 for early postoperative compared to other periods). Compared to the targeted dietary reference intake of 1.5 g/kg/d, there was a mean protein deficit of 0.8 g/kg/d in the early postoperative period. Only one patient (5%) met the protein dietary reference intake in the early postoperative period. CONCLUSION: In older adults undergoing cardiac surgery, dietary protein intake was substantially lower than the recommended target in the early postoperative period. Strategies to improve protein intake, particularly in frail older patients, may be considered as a therapeutic target.

Sex-Specific Determinants of Outcomes After Transcatheter Aortic Valve Replacement.

Background Women account for a large proportion of patients treated with transcatheter aortic valve replacement, yet there remain conflicting reports about the effect of sex on outcomes. Moreover, the sex-specific prevalence and prognostic impact of frailty has not been systematically studied in the context of transcatheter aortic valve replacement. Methods and Results A preplanned analysis of the FRAILTY-AVR study (Frailty Aortic Valve Replacement) was performed to analyze the determinants of outcomes in older women and men undergoing transcatheter aortic valve replacement. FRAILTY-AVR was a multinational, prospective, observational cohort assembled at 14 institutions in North America and Europe from 2012 to 2017. Multivariable logistic regression models were stratified by sex and adjusted for covariates. Interaction between sex and each of these covariates was assessed. The primary outcome was 12-month mortality, and the secondary outcome was 1-month composite mortality or major morbidity. The cohort consisted of 340 women and 419 men. Women were older and had higher predicted risk of mortality. Women were more likely to have physical frailty traits, but not cognitive or psychosocial frailty traits, and global indices of frailty were similarly associated with adverse events regardless of sex. Women were more likely to require discharge to a rehabilitation facility, particularly those with physical frailty at baseline, although their functional status was similar to men at 12 months. The risk of 1-month mortality or major morbidity was greater in women, particularly those treated with larger prostheses. The risk of 12-month mortality was not greater in women, with the exception of those with pulmonary hypertension, in whom, there was a significant interaction for increased mortality. Conclusions The present study highlights sex-specific differences in older adults undergoing transcatheter aortic valve replacement and draws attention to the impact of physical frailty in women and their potential risk associated with oversized prostheses and pulmonary hypertension.

Phase Angle as a Biomarker for Frailty and Postoperative Mortality: The BICS Study.

Background Phase angle (PA) is a bioimpedance measurement that is determined lean body mass and hydration status. Patients with low PA values are more likely to be frail, sarcopenic, or malnourished. Previous work has shown that low PA predicts adverse outcomes after cardiac surgery, but the effect of PA on survival has not previously been assessed in this setting. Methods and Results The BICS (Bioimpedance in Cardiac Surgery) study recruited 277 patients undergoing major cardiac surgery at 2 university-affiliated hospitals in Montreal, QC, Canada. Bioimpedance measurements as well as frailty and nutritional assessments were performed preoperatively. The primary outcome was all-cause mortality. Secondary outcomes were 30-day mortality, postoperative morbidity, and hospital length of stay. There were 10 deaths at 1 month of follow-up and 16 deaths at 12 months of follow-up. PA was associated with age, sex, body mass index, comorbidities, and frailty, as measured by the Short Physical Performance Battery and Fried scales. After adjusting for Society of Thoracic Surgeons-predicted mortality, lower PA was associated with higher mortality at 1 month (adjusted odds ratio, 3.57 per 1° decrease in PA ; 95% confidence interval, 1.35-9.47) and at 12 months (adjusted odds ratio, 3.03 per 1° decrease in PA ; 95% confidence interval, 1.30-7.09), a higher risk of overall morbidity (adjusted hazard ratio, 2.51 per 1° decrease in PA ; 95% confidence interval, 1.32-4.75), and a longer hospital length of stay (adjusted ß, 4.8 days per 1° decrease in PA ; 95% confidence interval, 1.3-8.2 days). Conclusions Low PA is associated with frailty and is predictive of mortality, morbidity, and length of stay after major cardiac surgery. Further work is needed to determine the responsiveness of PA to interventions aimed at reversing frailty.

Association of Depression With Mortality in Older Adults Undergoing Transcatheter or Surgical Aortic Valve Replacement.

Importance: Depression is increasingly recognized as a risk factor for adverse outcomes in cardiovascular disease. However, little is known about depression in older adults undergoing transcatheter (TAVR) or surgical (SAVR) aortic valve replacement. Objective: To determine the prevalence of depression and its association with all-cause mortality in older adults undergoing TAVR or SAVR. Design, Setting, and Participants: This preplanned analysis of the Frailty Aortic Valve Replacement (FRAILTY-AVR) prospective cohort study included 14 centers in 3 countries from November 15, 2011, through April 7, 2016. Individuals 70 years or older who underwent TAVR or SAVR were enrolled. Depressive symptoms were evaluated using the Geriatric Depression Scale Short Form at baseline and follow-up. Main Outcomes and Measures: All-cause mortality at 1 and 12 months after TAVR or SAVR. Logistic regression was used to determine the association of depression with mortality after adjusting for confounders such as frailty and cognitive impairment. Results: Among 1035 older adults (427 men [41.3%] and 608 women [58.7%]) with a mean (SD) age of 81.4 (6.1) years, 326 (31.5%) had a positive result of screening for depression, whereas only 89 (8.6%) had depression documented in their clinical record. After adjusting for clinical and geriatric confounders, baseline depression was found to be associated with mortality at 1 month (odds ratio [OR], 2.20; 95% CI, 1.18-4.10) and at 12 months (OR, 1.532; 95% CI, 1.03-2.24). Persistent depression, defined as baseline depression that was still present 6 months after the procedure, was associated with a 3-fold increase in mortality at 12 months (OR, 2.98; 95% CI, 1.08-8.20). Conclusions and Relevance: One in 3 older adults undergoing TAVR or SAVR had depressive symptoms at baseline and a higher risk of short-term and midterm mortality. Patients with persistent depressive symptoms at follow-up had the highest risk of mortality.

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).

Psoas Muscle Area and Length of Stay in Older Adults Undergoing Cardiac Operations.

BACKGROUND: Frailty assessment can help predict which older adults will experience adverse events after cardiac surgical procedures. Low muscle mass is a core component of frailty that is suboptimally captured by self-reported weight loss; refined measures using computed tomographic (CT) images have emerged and are predictive of outcomes in noncardiac surgical procedures. The objective of this study was to evaluate the association between CT muscle area and length of stay (LOS) after cardiac surgical procedures. METHODS: Frail patients who had a perioperative abdominal or thoracic CT scan were identified. The CT scans were analyzed to measure cross-sectional lean muscle area at the L4 vertebra (psoas muscle area [PMA], lumbar muscle area [LMA]) and the T4 vertebra (thoracic muscle area [TMA]). The associations of PMA, LMA, and TMA with frailty markers and postoperative LOS were investigated. RESULTS: Eighty-two patients were included; the mean age was 69.2 ± 9.97 years. Low muscle area was correlated with lower handgrip strength and short physical performance battery (SPPB) scores indicative of physical frailty. Postoperative LOS was correlated with PMA (R = -0.47, p = 0.004), LMA (R = -0.41, p = 0.01), and TMA (R = -0.29, p = 0.03). After adjustment for the predicted risk of prolonged LOS, age, sex, and body surface area, PMA remained significantly associated with LOS (ß = -2.35, 95% CI -4.48 to -0.22). The combination of low PMA and handgrip strength, indicative of sarcopenia, yielded the greatest incremental value in predicting LOS. CONCLUSIONS: Low PMA is a marker of physical frailty associated with increased LOS in older adults undergoing cardiac surgical procedures. Further research is necessary to validate PMA as a prognostic marker and therapeutic target in this vulnerable population.

Synergistic effect of inhibiting translation initiation in combination with cytotoxic agents in acute myelogenous leukemia cells.

We have previously shown that inhibition of translation initiation, using the small molecule inhibitor silvestrol, induces apoptosis in a pre-clinical murine lymphoma model when combined with daunorubicin. Silvestrol blocks ribosome recruitment by targeting the RNA helicase, eIF4A, which is required for this process. Here we investigate the sensitivity of acute myelogenous leukemia (AML) cell lines to protein synthesis inhibition in combination with the standard cytotoxic agents daunorubicin, etoposide, and cytarabine. Silvestrol shows synergy with standard-of-care agents in AML cell lines and synergizes with ABT-737, a small molecule inhibitor of Bcl-X(L) and Bcl-2. The in vitro synergy between silvestrol and the cytotoxic drugs used in AML therapy provides a basis for in vivo evaluation of these combinations.