A randomized controlled trial of renin-angiotensin-aldosterone system inhibitor management in patients admitted in hospital with COVID-19.

BACKGROUND: Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes. METHODS: The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-to-treat principle. RESULTS: Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06-2.62]; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016). CONCLUSION: RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.

The dynamic changes and sex differences of 147 immune-related proteins during acute COVID-19 in 580 individuals.

INTRODUCTION: Severe COVID-19 leads to important changes in circulating immune-related proteins. To date it has been difficult to understand their temporal relationship and identify cytokines that are drivers of severe COVID-19 outcomes and underlie differences in outcomes between sexes. Here, we measured 147 immune-related proteins during acute COVID-19 to investigate these questions. METHODS: We measured circulating protein abundances using the SOMAscan nucleic acid aptamer panel in two large independent hospital-based COVID-19 cohorts in Canada and the United States. We fit generalized additive models with cubic splines from the start of symptom onset to identify protein levels over the first 14 days of infection which were different between severe cases and controls, adjusting for age and sex. Severe cases were defined as individuals with COVID-19 requiring invasive or non-invasive mechanical respiratory support. RESULTS: 580 individuals were included in the analysis. Mean subject age was 64.3 (sd 18.1), and 47% were male. Of the 147 proteins, 69 showed a significant difference between cases and controls (p < 3.4 × 10-4). Three clusters were formed by 108 highly correlated proteins that replicated in both cohorts, making it difficult to determine which proteins have a true causal effect on severe COVID-19. Six proteins showed sex differences in levels over time, of which 3 were also associated with severe COVID-19: CCL26, IL1RL2, and IL3RA, providing insights to better understand the marked differences in outcomes by sex. CONCLUSIONS: Severe COVID-19 is associated with large changes in 69 immune-related proteins. Further, five proteins were associated with sex differences in outcomes. These results provide direct insights into immune-related proteins that are strongly influenced by severe COVID-19 infection.

Older Adults in the Cardiac Intensive Care Unit: Factoring Geriatric Syndromes in the Management, Prognosis, and Process of Care: A Scientific Statement From the American Heart Association.

Longevity is increasing, and more adults are living to the stage of life when age-related biological factors determine a higher likelihood of cardiovascular disease in a distinctive context of concurrent geriatric conditions. Older adults with cardiovascular disease are frequently admitted to cardiac intensive care units (CICUs), where care is commensurate with high age-related cardiovascular disease risks but where the associated geriatric conditions (including multimorbidity, polypharmacy, cognitive decline and delirium, and frailty) may be inadvertently exacerbated and destabilized. The CICU environment of procedures, new medications, sensory overload, sleep deprivation, prolonged bed rest, malnourishment, and sleep is usually inherently disruptive to older patients regardless of the excellence of cardiovascular disease care. Given these fundamental and broad challenges of patient aging, CICU management priorities and associated decision-making are particularly complex and in need of enhancements. In this American Heart Association statement, we examine age-related risks and describe some of the distinctive dynamics pertinent to older adults and emerging opportunities to enhance CICU care. Relevant assessment tools are discussed, as well as the need for additional clinical research to best advance CICU care for the already dominating and still expanding population of older adults.

Sarcopenia in cardiac surgery: Dual X-ray absorptiometry study from the McGill frailty registry.

BACKGROUND: To determine the prevalence and prognostic value of sarcopenia measured by dual x-ray absorptiometry (DXA) and physical performance tests in patients undergoing coronary artery bypass surgery or heart valve procedures. METHODS: Adults undergoing cardiac surgery were prospectively enrolled and completed a questionnaire, physical performance battery, and a DXA scan (GE Lunar) to measure appendicular muscle mass indexed to height2 (AMMI). Patients were categorized as sarcopenic based on European Working Group 2 guidelines if they had low AMMI defined as <7 kg/m2 for men or <5.5 kg/m2 for women, and low muscle strength defined as 5 chair rise time ≥15 seconds. Cox proportional hazards regression was used to test the association between sarcopenia and all-cause mortality over a median follow-up of 4.3 years. RESULTS: The cohort consisted of 141 patients with a mean age of 69.7 ± 10.0 years and 21% females. The prevalence rates of low AMMI, slow chair rise time, and sarcopenia (low AMMI and slow chair rise time) were 24%, 57%, 13%, respectively. The 4-year survival rate was 79% in the non-sarcopenic group as compared to 56% in the sarcopenic group (Log-rank P = 0.01). In the multivariable model, each standard deviation of decreasing AMMI and increasing chair rise time was associated with a hazard ratio for all-cause mortality of 1.84 (95% CI 1.18, 2.86) and 1.79 (95% CI 1.26, 2.54), respectively. CONCLUSION: Lower-extremity muscle strength and DXA-based muscle mass are objective indicators of sarcopenia that are independently predictive of all-cause mortality in older cardiac surgery patients.

Frailty: implications for clinical practice and public health.

Frailty is an emerging global health burden, with major implications for clinical practice and public health. The prevalence of frailty is expected to rise alongside rapid growth in the ageing population. The course of frailty is characterised by a decline in functioning across multiple physiological systems, accompanied by an increased vulnerability to stressors. Having frailty places a person at increased risk of adverse outcomes, including falls, hospitalisation, and mortality. Studies have shown a clear pattern of increased health-care costs and use associated with frailty. All older adults are at risk of developing frailty, although risk levels are substantially higher among those with comorbidities, low socioeconomic position, poor diet, and sedentary lifestyles. Lifestyle and clinical risk factors are potentially modifiable by specific interventions and preventive actions. The concept of frailty is increasingly being used in primary, acute, and specialist care. However, despite efforts over the past three decades, agreement on a standard instrument to identify frailty has not yet been achieved. In this Series paper, we provide an overview of the global impact and burden of frailty, the usefulness of the frailty concept in clinical practice, potential targets for frailty prevention, and directions that need to be explored in the future.

Restricted mean survival time of older adults with severe aortic stenosis referred for transcatheter aortic valve replacement.

BACKGROUND: Few studies have measured frailty as a potential reason for foregoing transcatheter aortic valve replacement (TAVR) in older adults with severe aortic stenosis (AS). This study sought to determine the impact of frailty and other clinician-cited reasons on restricted mean survival time (RMST). METHODS: An analysis of the McGill Frailty Registry was conducted between 2014 and 2018 at the McGill University Health Center Structural Valve Clinic. Consecutive nonsurgical patients referred for TAVR were included. In those that underwent balloon aortic valvuloplasty or medical management, the primary clinician-cited reason for foregoing TAVR was codified. Vital status was ascertained at 1 year and analysed using RMST and Kaplan-Meier analyses. RESULTS: The study consisted of 373 patients with a mean age of 82.4 years, of which 233 underwent TAVR and 140 did not. Patients who did not undergo TAVR were more likely to be nonagenarians, with left ventricular dysfunction, chronic kidney disease, dementia, disability, depression, malnutrition, and frailty. The primary clinician-cited reason was: comorbidity in 34%, frailty in 23%, procedural feasibility and risks in 16%, and mild or unrelated symptoms in 27%. Compared to the TAVR group, 1-year RMST was reduced by 2.0 months in the medical management group (95% CI 1.2, 2.7) and by 1.1 months in the valvuloplasty group (95% CI -0.2, 2.5). CONCLUSIONS: Patients with severe AS referred for TAVR may never undergo the procedure on the basis of comorbidity, frailty, procedural issues, and symptoms. The best treatment decision is one that follows from multi-disciplinary assessment encompassing frailty.

Comparative utility of frailty to a general prognostic score in identifying patients at risk for poor outcomes after aortic valve replacement.

BACKGROUND: Current guidelines recommend considering life expectancy before aortic valve replacement (AVR). We compared the performance of a general mortality index, the Lee index, to a frailty index. METHODS: We conducted a prospective cohort study of 246 older adults undergoing surgical (SAVR) or transcatheter aortic valve replacement (TAVR) at a single academic medical center. We compared performance of the Lee index to a deficit accumulation frailty index (FI). Logistic regression was used to assess the association of Lee index or FI with poor outcome, defined as death or functional decline with severe symptoms at 12 months. Discrimination was assessed using C-statistics. RESULTS: In the overall cohort, 44 experienced poor outcome (31 deaths, 13 functional decline with severe symptoms). The risk of poor outcome by Lee index quartiles was 6.8% (reference), 17.9% (odds ratio [OR], 3.0; 95% confidence interval, [0.9-10.2]), 20.0% (OR 3.4; [1.0-11.4]), and 34.0% (OR 7.1; [2.2-22.6]) (p-for-trend = 0.001). Risk of poor outcome by FI quartiles was 3.6% (reference), 10.3% (OR 3.1; [0.6-15.8]), 25.0% (OR 8.8; [1.9-41.0]), and 37.3% (OR 15.8; [3.5-71.1]) (p-for-trend< 0.001). The Lee index predicted the risk of poor outcome in the SAVR cohort Lee index (quartiles 1-4: 2.1, 4.0, 15.4, and 20.0%; p-for-trend = 0.04), but not in the TAVR cohort (quartiles 1-4: 27.3, 29.0, 21.3, 35.4%; p-for-trend = 0.42). In contrast, the FI did not predict the risk of poor outcome well in the SAVR cohort (quartiles 1-4: 2.3, 4.4, 15.8, and 0%; p-for-trend = 0.24), however in the TAVR cohort (quartiles 1-4: 9.1, 14.3, 29.7, and 40.7%; p-for-trend = 0.004). Compared to the Lee index, an FI demonstrated higher C-statistics in the overall (Lee index versus FI: 0.680 versus 0.735; p = 0.03) and TAVR (0.560 versus 0.644; p = 0.03) cohorts, but not SAVR cohort (0.724 versus 0.766; p = 0.09). CONCLUSIONS: While a general mortality index Lee index predicted death or functional decline with severe symptoms at 12 months well among SAVR patients, the FI derived from a multi-domain geriatric assessment better informs risk-stratification for high-risk TAVR patients.

Malnutrition and Mortality in Frail and Non-Frail Older Adults Undergoing Aortic Valve Replacement.

BACKGROUND: Older adults undergoing aortic valve replacement (AVR) are at risk for malnutrition. The association between preprocedural nutritional status and midterm mortality has yet to be determined. METHODS: The FRAILTY-AVR (Frailty in Aortic Valve Replacement) prospective multicenter cohort study was conducted between 2012 and 2017 in 14 centers in 3 countries. Patients ≥70 years of age who underwent transcatheter or surgical AVR were eligible. The Mini Nutritional Assessment-Short Form was assessed by trained observers preprocedure, with scores ≤7 of 14 considered malnourished and 8 to 11 of 14 considered at risk for malnutrition. The Short Performance Physical Battery was simultaneously assessed to measure physical frailty, with scores ≤5 of 12 considered severely frail and 6 to 8 of 12 considered mildly frail. The primary outcome was 1-year all-cause mortality, and the secondary outcome was 30-day composite mortality or major morbidity. Multivariable regression models were used to adjust for potential confounders. RESULTS: There were 1158 patients (727 transcatheter AVR and 431 surgical AVR), with 41.5% females, a mean age of 81.3 years, a mean body mass index of 27.5 kg/m2, and a mean Society of Thoracic Surgeons-Predicted Risk of Mortality of 5.1%. Overall, 8.7% of patients were classified as malnourished and 32.8% were at risk for malnutrition. Mini Nutritional Assessment-Short Form scores were modestly correlated with Short Performance Physical Battery scores (Spearman R=0.31, P<0.001). There were 126 deaths in the transcatheter AVR group (19.1 per 100 patient-years) and 30 deaths in the surgical AVR group (7.5 per 100 patient-years). Malnourished patients had a nearly 3-fold higher crude risk of 1-year mortality compared with those with normal nutritional status (28% versus 10%, P<0.001). After adjustment for frailty, Society of Thoracic Surgeons-Predicted Risk of Mortality, and procedure type, preprocedural nutritional status was a significant predictor of 1-year mortality (odds ratio, 1.08 per Mini Nutritional Assessment-Short Form point; 95% CI, 1.01-1.16) and of the 30-day composite safety end point (odds ratio, 1.06 per Mini Nutritional Assessment-Short Form point; 95% CI, 1.001-1.12). CONCLUSIONS: Preprocedural nutritional status is associated with mortality in older adults undergoing AVR. Clinical trials are needed to determine whether pre- and postprocedural nutritional interventions can improve clinical outcomes in these vulnerable patients.

Frailty assessment in older adults undergoing interventions for peripheral arterial disease.

OBJECTIVE: Frailty is a multidimensional syndrome that influences postoperative morbidity and mortality after vascular procedures; however, its integration in clinical practice has been limited, given the lack of consensus on how to measure it. This study sought to compare the incremental predictive value of six different nonphysical performance frailty scales to predict poor outcomes after interventions for peripheral arterial disease (PAD). METHODS: This preplanned analysis of the FRailty Assessment In Lower Extremity arterial Disease (FRAILED) prospective cohort included two centers recruiting patients between July 1, 2015, and October 1, 2016. Individuals who underwent vascular interventions for Rutherford class 3 or higher PAD were enrolled. The following scales were compared: Edmonton Frail Scale, Groningen Frailty Indicator (GFI), modified Essential Frailty Toolset (mEFT), modified Frailty Index, Multidimensional Prognostic Index, and the Risk Analysis Index-C. The primary end point was a composite of all-cause mortality and major disability at 12 months after the procedure. The secondary end point was length of stay. Logistic regression was used to determine the association of frailty with the primary end point after adjusting for confounders. To compare the incremental predictive value of each frailty scale, model performance statistics were calculated. RESULTS: The cohort was composed of 148 patients with a mean age of 70 years. Depending on the scale used, the prevalence of frailty ranged from 16% to 70%. Frailty as measured by the GFI (adjusted odds ratio, 1.76; 95% confidence interval, 1.14-2.72) and mEFT (adjusted odds ratio, 2.71; 95% confidence interval, 1.29-5.73) predicted mortality and worsening disability at 12 months after interventions for PAD. Furthermore, there was statistically significant C-statistic, Bayesian information criterion, and integrated discrimination improvement when the GFI and mEFT were added to the baseline model. Frailty was not associated with length of stay. CONCLUSIONS: Frailty is associated with mortality and worsening disability after interventions for PAD. The GFI and mEFT performed well and identified vulnerable older adults who are at risk of poor outcomes after interventions for PAD and recommended for use in this setting.

Scoping review of frailty in vascular surgery.

OBJECTIVE: This review sought to describe the current state of knowledge of the impact of frailty on perioperative clinical outcomes in patients undergoing vascular interventions. METHODS: A scoping review of the literature from both PubMed and Ovid Embase databases was conducted to identify relevant English- and French-language articles published from inception to May 31, 2018. Patients undergoing vascular surgery interventions were included. RESULTS: Twenty-three studies have addressed the prevalence or prognostic impact of frailty in patients undergoing vascular surgery procedures. The prevalence of frailty ranged from 20% to 60%, and notably 14 different frailty assessments were used in these studies. Frailty was associated with increased comorbid status, prolonged length of stay, discharge to assisted living facility, loss of independence, postoperative morbidity, and all-cause mortality. CONCLUSIONS: There are a variety of heterogeneous tools to measure frailty in patients undergoing vascular surgery interventions. The prevalence of frailty varies by the scale used to measure it, as does its predictive value. Clinicians and surgeons should be sensitized to the importance of assessing frailty preoperatively in older adults undergoing vascular surgery and using it to assist in the decision-making process and allocation of surgical resources.

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.

CoreSlicer: a web toolkit for analytic morphomics.

BACKGROUND: Analytic morphomics, or more simply, "morphomics," refers to the measurement of specific biomarkers of body composition from medical imaging, most commonly computed tomography (CT) images. An emerging body of literature supports the use of morphomic markers measured on single-slice CT images for risk prediction in a range of clinical populations. However, uptake by healthcare providers been limited due to the lack of clinician-friendly software to facilitate measurements. The objectives of this study were to describe the interface and functionality of CoreSlicer- a free and open-source web-based interface aiming to facilitate measurement of analytic morphomics by clinicians - and to validate muscle and fat measurements performed in CoreSlicer against reference software. RESULTS: Measurements of muscle and fat obtained in CoreSlicer show high agreement with established reference software. CoreSlicer features a full set of DICOM viewing tools and extensible plugin interface to facilitate rapid prototyping and validation of new morphomic markers by researchers. We present published studies illustrating the use of CoreSlicer by clinicians with no prior knowledge of medical image segmentation techniques and no formal training in radiology, where CoreSlicer was successfully used to predict operative risk in three distinct populations of cardiovascular patients. CONCLUSIONS: CoreSlicer enables extraction of morphomic markers from CT images by non-technically skilled clinicians. Measurements were reproducible and accurate in relation to reference software.

Screening for older inpatients at risk for long length of stay: which clinical tool to use?

BACKGROUND: Screening for inpatients at risk for long length of stay (LOS) is the first step of an effective hospital care plan for older inpatients. This study aims, in older adults admitted to a geriatric acute care ward, to examine and compare the 6-item brief geriatric assessment (BGA) and the "Programme de Recherche sur l'Intégration des Services pour le Maintien de l'Autonomie" (PRISMA-7) risk levels with long LOS, and to establish their performance criteria (i.e., sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios) for LOS. METHODS: Based on an observational, retrospective, cohort design, 166 inpatients aged ≥75 admitted to a geriatric acute care ward of a McGill University-affiliated hospital (Montreal, Quebec, Canada) were recruited. The risk levels of the 6-item BGA (low, moderate and high) and the PRISMA-7 (low versus high) were calculated from a baseline assessment. The LOS was subsequently calculated in number of days. RESULTS: Only the 6-item BGA high risk level was associated with a long LOS (Odds ratio = 1.1 with P = 0.028 and Hazard ratio = 2.1 with P = 0.004). Kaplan-Meier distributions showed that there was no significant difference in the delay of hospital discharge between the low and high-risk level reported by the PRISMA-7 (P = 0.381), whereas the 6-item BGA three risk levels differed significantly (P = 0.008), with individuals at high risk levels being discharged later when compared to those with low (P = 0.001) and moderate (P = 0.019) risk levels. Both tools' performance criteria were poor (i.e., < 0.70), except for PRISMA-7's sensitivity which was 100%. CONCLUSION: The 6-item BGA risk levels were associated with LOS, low risk-level being associated with short LOS and high-risk level with long LOS, but no association was reported with the PRISMA-7 risk levels. Both tools had poor performance criteria for long LOS, suggesting that they cannot be used as prognostic tools with current scientific knowledge.

Impact of an invasive strategy in the elderly hospitalized with acute coronary syndrome with emphasis on the nonagenarians.

BACKGROUND: Published data about nonagenarians with acute coronary syndrome (ACS) were mainly descriptive and limited by small sample sizes and unadjusted outcomes. We aim to describe the characteristics, management, and the impact of an invasive strategy on major adverse events in elderly patients hospitalized with ACS with focus on the nonagerians. METHODS AND RESULTS: We analyzed data collected as part of the AMI-OPTIMA study, a cluster-randomized study of knowledge translation intervention versus usual care on optimal discharge medications in patients admitted with ACS at 24 Canadian hospitals. To determine whether an invasive strategy improved outcomes in the elderly, we used inverse probability weighting to adjust for confounders between patients who underwent invasive versus conservative strategies. Of 4,569 consecutive patients: 2,395 (52%) were <70 years old, 1,031 (23%) were septuagenarians, 941 (21%) were octogenarians, and 202 (4.4%) were nonagenarians. An invasive strategy was associated with reduced in-hospital all-cause mortality in all age groups: 1.1% versus 3.8% in patients <70 years old (P < 0.001), 2.9% versus 7.4% in septuagenarians (P < 0.001), 5.1% versus 14.7% in octogenarians (P < 0.001), and 12.0% versus 25.1% in nonagenarians (P = 0.001). An invasive strategy was also associated with higher thrombolysis in myocardial infarction major bleeds in the nonagenarians (9.0% vs. 2.0%; P = 0.003). CONCLUSIONS: The reduction in in-hospital mortality associated with an invasive strategy in elderly and nonagenarians presented with ACS is generating hypothesis and merits further studies to confirm these benefits and to guide clinicians in the management of these high-risk patients.

Gait Speed Predicts 30-Day Mortality After Transcatheter Aortic Valve Replacement: Results From the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry.

BACKGROUND: Surgical risk scores do not include frailty assessments (eg, gait speed), which are of particular importance for patients with severe aortic stenosis considering transcatheter aortic valve replacement. METHODS AND RESULTS: We assessed the association of 5-m gait speed with outcomes in a cohort of 8039 patients who underwent transcatheter aortic valve replacement (November 2011-June 2014) and were included in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for Society of Thoracic Surgeons-predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The overall median gait speed was 0.63 m/s (25th-75th percentile, 0.47-0.79 m/s), with the slowest walkers (<0.5 m/s) constituting 28%, slow walkers (0.5-0.83 m/s) making up 48%, and normal walkers (>0.83 m/s) constituting 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively (P<0.001). Each 0.2-m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio, 1.11; 95% confidence interval, 1.01-1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio, 1.35; 95% confidence interval, 1.01-1.80), significantly longer hospital stays, and a lower probability of being discharged to home. CONCLUSIONS: Gait speed is independently associated with 30-day mortality after transcatheter aortic valve replacement. Identification of frail patients with the slowest gait speeds facilitates preprocedural evaluation and anticipation of a higher level of postprocedural care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01737528.

Complications Associated With Nitrate Use in Patients Presenting With Acute Pulmonary Edema and Concomitant Moderate or Severe Aortic Stenosis.

STUDY OBJECTIVE: We evaluate the incidence of complications associated with the use of nitrates in patients presenting with acute pulmonary edema and concomitant moderate or severe aortic stenosis compared with patients without aortic stenosis. Nitrates are contraindicated in severe aortic stenosis because of the theoretical yet unproven risk of precipitating profound hypotension. METHODS: A cohort design with retrospective chart review study was conducted at two Canadian hospitals. Patients with aortic stenosis (moderate or severe) and without aortic stenosis were included if they presented with acute cardiogenic pulmonary edema, received intravenous or sublingual nitroglycerin, and had an echocardiography report available. The primary outcome was clinically relevant hypotension, defined as hypotension leading to any of the following predefined events: nitroglycerin discontinuation, intravenous fluid bolus, vasopressor use, or cardiac arrest. The secondary outcome was sustained hypotension, defined as a systolic blood pressure less than 90 mm Hg and lasting greater than or equal to 30 minutes. RESULTS: The cohort consisted of 195 episodes of acute pulmonary edema, representing 65 episodes with severe aortic stenosis (N=65) and an equal number of matched episodes with moderate aortic stenosis (N=65) and no aortic stenosis (N=65). Nitroglycerin was administered intravenously only in 70% of cases, intravenously and sublingually in 25%, and sublingually only in the remaining 5%. After adjustment for sex, initial systolic blood pressure, furosemide dose, and use of noninvasive ventilation, moderate and severe aortic stenosis were not associated with clinically relevant hypotension after receipt of nitroglycerin (adjusted odds ratio [OR] 0.97, 95% confidence interval [CI] 0.40 to 2.37 for moderate aortic stenosis; adjusted OR 0.99, 95% CI 0.41 to 2.41 for severe aortic stenosis). The incidence of clinically relevant hypotension was 26.2% for moderate and severe aortic stenosis and 23.1% in the no aortic stenosis reference group. The secondary outcome of sustained hypotension occurred in 29.2% of patients with severe aortic stenosis, 16.9% with moderate aortic stenosis, and 13.8% in the no aortic stenosis group (adjusted OR for severe aortic stenosis 2.34; 95% CI 0.91 to 6.01). CONCLUSION: In this retrospective study, neither moderate nor severe aortic stenosis was associated with a greater risk of clinically relevant hypotension requiring intervention when nitroglycerin was used for acute pulmonary edema. Future studies should investigate safety and efficacy of nitroglycerin for patients with aortic stenosis because this study was limited by a small sample size and design limitations. Cautious use of nitroglycerin in patients with moderate or severe aortic stenosis and presenting with acute pulmonary edema may be a safer strategy than traditionally thought.

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.

Prognostic and Therapeutic Implications of Frailty in Older Adults with Heart Failure.

Frailty is increasingly recognized in older adults with cardiovascular disease, particularly in those with heart failure (HF). A growing body of evidence has shown that frailty has a negative effect on survival, hospitalizations, disability, and quality of life. Beyond frailty, additional domains captured by a comprehensive geriatric assessment contribute incremental value in predicting outcomes and identifying treatment targets. Exercise training is ideally suited to this setting as it can concomitantly improve physical frailty and HF symptoms. Multidisciplinary disease management programs offer a number of benefits for frail HF patients; invasive procedures carry a higher risk of morbidity than in non-frail counterparts, and evidence-based drugs and devices have an uncertain value and warrant further research. While more data accrues, difficult therapeutic decisions should be individualized using a shared patient-centered decision making approach.