Preoperative Rehabilitation Is Feasible in the Weeks Prior to Surgery and Significantly Improves Functional Performance.

BACKGROUND: Frailty is a multidimensional state of increased vulnerability. Frail patients are at increased risk for poor surgical outcomes. Prior research demonstrates that rehabilitation strategies deployed after surgery improve outcomes by building strength. OBJECTIVES: Examine the feasibility and impact of a novel, multi-faceted prehabilitation intervention for frail patients before surgery. DESIGN: Single arm clinical trial. SETTING: Veterans Affairs hospital. PARTICIPANTS: Patients preparing for major abdominal, urological, thoracic, or cardiac surgery with frailty identified as a Risk Analysis Index≥30. INTERVENTION: Prehabilitation started in a supervised setting to establish safety and then transitioned to home-based exercise with weekly telephone coaching by exercise physiologists. Prehabilitation included (a)strength and coordination training; (b)respiratory muscle training (IMT); (c)aerobic conditioning; and (d)nutritional coaching and supplementation. Prehabilitation length was tailored to the 4-6 week time lag typically preceding each participant's normally scheduled surgery. MEASUREMENTS: Functional performance and patient surveys were assessed at baseline, every other week during prehabilitation, and then 30 and 90 days after surgery. Within-person changes were estimated using linear mixed models. RESULTS: 43 patients completed baseline assessments; 36(84%) completed a median 5(range 3-10) weeks of prehabilitation before surgery; 32(74%) were retained through 90-day follow-up. Baseline function was relatively low. Exercise logs show participants completed 94% of supervised exercise, 78% of prescribed IMT and 74% of home-based exercise. Between baseline and day of surgery, timed-up-and-go decreased 2.3 seconds, gait speed increased 0.1 meters/second, six-minute walk test increased 41.7 meters, and the time to complete 5 chair rises decreased 1.6 seconds(all P≤0.007). Maximum and mean inspiratory and expiratory pressures increased 4.5, 7.3, 14.1 and 13.5 centimeters of water, respectively(all P≤0.041). CONCLUSIONS: Prehabilitation is feasible before major surgery and achieves clinically meaningful improvements in functional performance that may impact postoperative outcomes and recovery. These data support rationale for a larger trial powered to detect differences in postoperative outcomes.

Muscle Area and Density Assessed by Abdominal Computed Tomography in Healthy Adults: Effect of Normal Aging and Derivation of Reference Values.

BACKGROUND: A growing body of evidence has demonstrated the prognostic value of skeletal muscle area and quality measured by computed tomography (CT) as biomarkers of sarcopenia and frailty. However, there exists little data in normal healthy subjects to inform reference values and determine the effects of advancing age and sex on CT muscle parameters. METHODS: Abdominal CT images of patients (20-80 years of age) presenting to the emergency department with benign abdominal symptoms and no significant medical comorbidities were retrospectively collected from 2014 to 2017. Psoas and abdominal wall muscle area (PMA, WMA) and density (PMD, WMD) at the level of the L4 vertebrae were measured with the CoreSlicer.com web app. The normal reference range was computed by non-parameteric 2.5th and 97.5th percentiles stratified by sex and restricted by age to the younger subgroup (20-39 years of age). RESULTS: The cohort consisted of 390 otherwise healthy patients (162 males, 228 females). The lower reference range for PMA was <22.0 cm2 in males and <11.1 cm2 in females, and for WMA was <112.2 cm2 in males and <75.6 cm2 in females. There was a graded decline observed in PMA and WMA among older compared to younger adults (especially ≥60 years of age) (P<0.001) and among females compared to males (P<0.001). There was also a graded decline observed in PMD and WMD among older compared to younger adults (P<0.001), irrespective of sex. CONCLUSION: This study has defined the normal reference values and age-associated down-trend for CT muscle parameters at L4 in a healthy population using an accessible web-based software, which help contextualize and interpret these imaging biomarkers of sarcopenia in clinical care.

Rationale and Design of the TARGET-EFT Trial: Multicomponent Intervention for Frail and Pre-frail Patients Hospitalized with Acute Cardiac Conditions.

BACKGROUND: With the aging population and rising rates of cardiovascular disease (CVD), cardiologists and cardiac surgeons are encountering a growing number of frail older patients that have complex cardiac and non-cardiac issues. Measuring frailty provides valuable prognostic information to help personalize treatment decisions. However, there is minimal evidence on multicomponent frailty interventions in this setting. The TARGET-EFT (The MulTicomponent Acute Intervention in FRail GEriatric PaTients with cardiovascular disease using the Essential Frailty Toolset) trial aims to target physical and non-physical frailty deficits to improve health-related quality of life and hospital-acquired disability in frail patients hospitalized with CVD. METHODS: The TARGET-EFT trial is a single-center parallel-group randomized clinical trial in frail and pre-frail older adults ≥65 years admitted to the cardiovascular unit (CVU) at the Jewish General Hospital, Montreal, Quebec. The trial will compare usual inpatient care to a multicomponent intervention targeting physical weakness, cognitive impairment, malnutrition, and anemia. Outcomes of interest in both groups will be assessed at three time points: (1) study enrollment, (2) discharge from the CVU, and (3) 30 days after hospital discharge. CONCLUSIONS: The overarching goal is to treat patients' frailty in parallel with their CVD, and in doing so, optimize patient functional losses while in-hospital and shortly thereafter. The results of this trial will inform best practices for patient-centered care in this vulnerable patient group.

Intersecting Genetics of Frailty and Cardiovascular Disease.

OBJECTIVES: To determine the genetic correlates of physical frailty and sarcopenia, focusing on single nucleotide polymorphisms (SNPs) in genome-wide association studies (GWAS), and to explore the genetic overlap of frailty with cardiovascular disease (CVD) and its risk factors. METHODS: PubMed was systematically searched for GWAS studies investigating the association between SNPs and objective measures of physical frailty or sarcopenia. SNPs were retained if they were associated with one of the phenotypes of interest by a p-value of 5.0x10-8 or less. RESULTS: Ten studies were included, with a total of 237 SNPs in 181 genes being associated with physical frailty or sarcopenia; as measured by handgrip strength or lean (muscle) mass. These genes were cross-referenced in the GWAS Catalog, and many of them were found to be associated with CVD or metabolic syndrome. CONCLUSIONS: Evidence from GWAS has shown that frailty is associated with common genetic polymorphisms. Many of these polymorphisms have been implicated in CVD, supporting the hypothesis of a shared pathophysiology between these entities. Future studies are eagerly anticipated to map out the mechanistic links and discover therapeutic targets and novel biomarkers for frailty.

Moving Towards Common Data Elements and Core Outcome Measures in Frailty Research.

With aging populations around the world, frailty is becoming more prevalent increasing the need for health systems and social systems to deliver optimal evidence based care. However, in spite of the growing number of frailty publications, high-quality evidence for decision making is often lacking. Inadequate descriptions of the populations enrolled including frailty severity and frailty conceptualization, lack of use of validated frailty assessment tools, utilization of different frailty instruments between studies, and variation in reported outcomes impairs the ability to interpret, generalize and implement the research findings. The utilization of common data elements (CDEs) and core outcome measures (COMs) in clinical trials is increasingly being adopted to address such concerns. To catalyze the development and use of CDEs and COMs for future frailty studies, the Canadian Frailty Network (www.cfn-nce.ca; CFN), a not-for-profit pan-Canadian nationally-funded research network, convened an international group of experts to examine the issue and plan the path forward. The meeting was structured to allow for an examination of current frailty evidence, ability to learn from other COMs and CDEs initiatives, discussions about specific considerations for frailty COMs and CDEs and finally the identification of the necessary steps for a COMs and CDEs consensus initiative going forward. It was agreed at the onset of the meeting that a statement based on the meeting would be published and herein we report the statement.

Proceedings of the Canadian Frailty Network Workshop: Identifying Biomarkers of Frailty to Support Frailty Risk Assessment, Diagnosis and Prognosis. Toronto, January 15, 2018.

The Canadian Frailty Network (CFN), a pan-Canadian not-for-profit organization funded by the Government of Canada through the Networks of Centres of Excellence Program, is dedicated to improving the care of older Canadians living with frailty. The CFN has partnered with the Canadian Longitudinal Study on Aging (CLSA) to measure potential frailty biomarkers in biological samples (whole blood, plasma, urine) collected in over 30,000 CLSA participants. CFN hosted a workshop in Toronto on January 15 2018, bringing together experts in the field of biomarkers, aging and frailty. The overall objectives of the workshop were to start building a consensus on potential frailty biomarker domains and identify specific frailty biomarkers to be measured in the CLSA biological samples. The workshop was structured with presentations in the morning to frame the discussions for the afternoon session, which was organized as a free-flowing discussion to benefit from the expertise of the participants. Participants and speakers were from Canada, Italy, Spain, United Kingdom and the United States. Herein we provide pertinent background information, a summary of all the presentations with key figures and tables, and the distillation of the discussions. In addition, moving forward, the principles CFN will use to approach frailty biomarker research and development are outlined. Findings from the workshop are helping CFN and CLSA plan and conduct the analysis of biomarkers in the CLSA samples and which will inform a follow-up data access competition.

Psoas Muscle Area Predicts All-Cause Mortality After Endovascular and Open Aortic Aneurysm Repair.

OBJECTIVE: Psoas muscle area (PMA) is a validated surrogate for muscle mass that can be easily measured from a clinical CT scan. This study sought to determine whether PMA was associated with post-operative mortality after endovascular or open aortic aneurysm repair. METHODS: A retrospective review was undertaken of patients who underwent elective endovascular or open aortic aneurysm repair between 2010 and 2015 at a tertiary vascular center in Montreal, Quebec, Canada. Pre-operative CT scan images were analyzed with the CoreSlicer.com software tool to measure PMA at the axial level of the L4 vertebrae. Measurements were made by two independent observers blinded to clinical data. The primary endpoint was all-cause mortality. RESULTS: The cohort consisted of 149 patients with a mean age of 75.6 ± 8.8 years. The mean PMA was 24.0 ± 5.8 cm2 in males, and 14.3 ± 3.1 cm2 in females. There were 31 deaths over a mean follow-up of 22.4 months. After adjusting for age, sex, revised cardiac risk index, and surgical approach, Cox regression revealed a graded association between PMA and all-cause mortality with a hazard ratio of 0.86 per cm2 (95% CI 0.79-0.93). Addition of PMA to the model with the clinical covariates resulted in an improvement in C-statistic from 0.57 to 0.67, and BIC from 307 to 301 (with lower BIC values preferred). CONCLUSIONS: PMA is independently associated with all-cause mortality after elective endovascular and open aortic aneurysm repair, and may be integrated into the pre-operative risk assessment to optimize care in high-risk frail patients.

Systematic review of fibrinolytic-facilitated percutaneous coronary intervention: potential benefits and future challenges.

BACKGROUND: Facilitated percutaneous coronary intervention (PCI) is defined as the administration of fibrinolytic therapy and/or glycoprotein (GP) IIb/IIIa inhibitors to minimize myocardial ischemia time while waiting for PCI. A pooled meta-analysis suggested that facilitated PCI was associated with higher rates of mortality and morbidity compared with nonfacilitated PCI. OBJECTIVE: The heterogeneous and complex trials of facilitated PCI were systematically reviewed to identify where this strategy may be beneficial and deserving of further research. METHODS: MEDLINE, EMBASE, the Cochrane database, the Internet and conference proceedings were searched to obtain relevant trials. Human studies that randomly assigned patients to fibrinolytic-facilitated PCI (administration of fibrinolytic therapy alone or in combination with GP IIb/IIIa inhibitors before angiography) versus nonfacilitated PCI were included. RESULTS: Nine trials encompassing 3836 patients were reviewed. The facilitated PCI strategy was fibrinolytic therapy alone in seven trials and half-dose fibrinolytic therapy plus GP IIb/IIIa inhibitors in two trials. In patients who had fibrinolysis less than 2 h after symptom onset (mainly in the prehospital setting) and/or slightly delayed PCI 3 h to 24 h after fibrinolysis, facilitated PCI was associated with the greatest Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow and a trend toward reduced mortality. Overall, facilitated PCI was associated with increased intracranial hemorrhage and reinfarction. Combining half-dose fibrinolytic therapy and GP IIb/IIIa inhibitors reduced reinfarction but increased major bleeding. CONCLUSIONS: Facilitated PCI cannot be recommended outside of experimental protocols at this time. Further research should focus on selecting patients with higher benefit-to-risk ratios and performing prehospital fibrinolysis with optimal antiplatelet or antithrombin therapy, as well as slightly delayed PCI in patients who are stable or geographically removed from PCI facilities.