PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation: Part 2: Study results-prostheses, positions, and economic development.

Objectives: The Prospective Randomized On-X Mechanical Prosthesis Versus St Jude Medical Mechanical Prosthesis Evaluation (PROSE) trial purpose was to investigate whether a current-generation mechanical prosthesis (On-X; On-X Life Technologies/Artivion Inc) reduced the incidence of thromboembolic-related complications compared with a previous-generation mechanical prosthesis (St Jude Medical Mechanical Prosthesis; Abbott/St Jude Medical). This second report documents the valve-related complications by individual prostheses and by Western and Developing populations. Methods: The PROSE trial study was conducted in 28 worldwide centers and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The study protocol, and analyses of 10 demographic variables and 24 risk factors were published in detail in 2021. Results: The total patient population (N = 855) included patients receiving an On-X valve (n = 462) and a St Jude Medical valve (n = 393). The overall freedom evaluation showed no differences at 5 years between the prostheses for thromboembolism or for valve thrombosis. There were also no differences in mortality. There were several differences between Developing and Western populations. The freedom relations at 5 years for mortality favored Western over Developing populations. Valve thrombosis was differentiated by position and site: aortic < mitral (P = .007) and Western < Developing (P = .005). In the mitral position there were no cases in Western populations, whereas there were 8 in Developing populations (P = .217). Conclusions: The On-X valve and St Jude Medical valve performed equally well in the study with no differences found. The only differentiation occurred with valve thrombosis in the mitral position more than the aortic position and occurring in Developing more than Western populations. The occurrence of valve thrombosis was also related to a younger population possibly due to anticoagulation compliance based on record review.

PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation : Part 1(Patient Dynamics): Preoperative demographics and preoperative and operative risk factors.

OBJECTIVES: The PROSE trial purpose is to investigate whether the incidence of thromboembolic-related complications is reduced with a current generation mechanical prosthesis (On-X Life Technologies/CryoLife Inc.-On-X) compared with a previous generation mechanical prosthesis (St Jude Medical-SJM). The primary purpose of the initial report is to document the preoperative demographics, and the preoperative and operative risk factors by individual prosthesis and by Western and Developing populations. METHODS: The PROSE study was conducted in 28 worldwide centres and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The preoperative demographics incorporated age, gender, functional class, etiology, prosthetic degeneration, primary rhythm, primary valve lesion, weight, height, BSA and BMI. The preoperative and operative evaluation incorporated 24 risk factors. RESULTS: The total patient population (855) incorporated On-X population (462) and the St Jude Medical population (393). There was no significant difference of any of the preoperative demographics between the On-X and SJM groups. The preoperative and operative risk factors evaluation showed there was no significant difference between the On-X and St Jude Medical populations. The preoperative and operative risk factors by valve position (aortic and mitral) also documented no differentiation. The dominant preoperative demographics of the Western world population were older age, male gender, sinus rhythm, aortic stenosis, congenital aortic lesion, and mitral regurgitation. The dominant demographics of the Developing world population were rheumatic etiology, atrial fibrillation, aortic regurgitation, mixed aortic lesions, mitral stenosis and mixed mitral lesions. The Developing world group had only one significant risk factor, congestive heart failure. The majority of the preoperative and operative risk factors were significant in the Western world population. CONCLUSIONS: The preoperative demographics do not differentiate the prostheses but do differentiate the Western and Developing world populations. The preoperative and operative risk factors do not differentiate the prostheses BUT do differentiate the Western and Developing world populations.

The Essential Frailty Toolset in Older Adults Undergoing Coronary Artery Bypass Surgery.

Background The Essential Frailty Toolset (EFT) was shown to be easy to use and predictive of adverse events in patients undergoing aortic valve replacement procedures. The objective of this study was to evaluate the EFT in patients undergoing coronary artery bypass grafting procedures. Methods and Results The McGill Frailty Registry prospectively included patients ≥60 years of age undergoing urgent or elective isolated coronary artery bypass grafting between 2011 and 2018 at 2 hospitals. The preoperative EFT was scored 0 to 5 points as a function of timed chair rises, Mini-Mental Status Examination, serum albumin, and hemoglobin. The primary outcome was all-cause mortality assessed by Cox proportional hazards regression. The cohort consisted of 500 patients with a mean age of 71.4 ± 6.4 years, of which 27% presented with acute coronary syndromes requiring urgent surgery. The mean EFT was 1.3 ± 1.1 points, 132 (26%) were nonfrail, 298 (60%) were prefrail, and 70 (14%) were frail. Over a median follow-up of 4.0 years, 78 deaths were observed. In nonfrail, prefrail, and frail patients, survival at 1 year was 98%, 95%, and 91%, and at 5 years was 89%, 83%, and 63% (P<0.001). After adjustment, each incremental EFT point was associated with a hazard ratio of 1.28 (95% CI, 1.05-1.56) and frail patients had a 3-fold increase in all-cause mortality. Conclusions The EFT is a pragmatic and highly prognostic tool to assess frailty and guide decisions for coronary artery bypass grafting in older adults. Furthermore, the EFT may be actionable through targeted interventions such as cardiac rehabilitation and nutritional optimization.

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.

Standardizing Postoperative Complications-Validating the Clavien-Dindo Complications Classification in Cardiac Surgery.

Cardiac surgery lacks a method for quantifying postoperative morbidities. The Clavien-Dindo Complications Classification (CDCC) and the Comprehensive Complication Index (CCI) were successfully implemented as outcome reporting methods in other surgical specialties. This study aims to validate these complication scales in cardiac surgery. Between 2010 and 2019, we prospectively collected data on 41,218 adult patients (73% men, mean age 67 ± 11 years) undergoing cardiac surgery at 6 university hospitals. Complications were graded using the CDCC based on the complication's treatment invasiveness with adaptations for common treatments in cardiac surgery. CCI were calculated, representing multiple complications on a scale of 0 (no complication) to 100 (death). Associations with predictors of poor outcome were assessed using mixed-effects models accounting for center as a random effect. CDCC grade was 0 in 23.0%, I in 11.4%, II in 35.3%, IIIa in 6.4%, IIIb in 2.6%, IVa in 16.1%, IVb in 2.1%, and V in 3.1%. Median CCI was 23 (9, 40). A change from lowest to highest observed CDCC grade was associated with an increase in the Society of Thoracic Surgeons mortality score from 1.1% to 4.7%, surgery duration from 177 to 233 minutes, and hospital stay from 5.2 to 17 days (all P < 0.0001). The CCI also increased with greater procedure complexity (P < 0.0001). Increase in CDCC/CCI is associated with greater comorbidities, surgery durations, lengths of stay, and procedure complexity, accurately reflecting the nuances of the adult cardiac surgery postoperative course. These have great potential for uniform outcome reporting and quality improvement initiatives.

Frailty and Bleeding in Older Adults Undergoing TAVR or SAVR: Insights From the FRAILTY-AVR Study.

OBJECTIVES: The aim of this study was to examine the value of frailty to predict in-hospital major bleeding and determine its impact on mid-term mortality following transcatheter (TAVR) or surgical (SAVR) aortic valve replacement. BACKGROUND: Bleeding complications are harbingers of mortality and major morbidity in patients undergoing TAVR or SAVR. Despite the high prevalence of frailty in this population, little is known about its effects on bleeding risk. METHODS: A post hoc analysis was performed of the multinational FRAILTY-AVR (Frailty Aortic Valve Replacement) cohort study, which prospectively enrolled older adults ≥70 years of age undergoing TAVR or SAVR. Trained researchers assessed frailty using a questionnaire and physical performance battery pre-procedure and ascertained clinical data from the electronic health record. The primary endpoint was major or life-threatening bleeding during the index hospitalization, and the secondary endpoint was units of packed red blood cells transfused. RESULTS: The cohort consisted of 1,195 patients with a mean age of 81.3 ± 6.0 years. The incidence of life-threatening bleeding, major bleeding with a clinically apparent source, and major bleeding without a clinically apparent source was, respectively, 3%, 6%, and 9% in the TAVR group and 8%, 10%, and 31% in the SAVR group. Frailty measured using the Essential Frailty Toolset was an independent predictor of major bleeding and packed red blood cell transfusions in both groups. Major bleeding was associated with a 3-fold increase in 1-year mortality following TAVR (odds ratio: 3.40; 95% confidence interval: 2.22 to 5.21) and SAVR (odds ratio: 2.79; 95% confidence interval: 1.25 to 6.21). CONCLUSIONS: Frailty is associated with post-procedural major bleeding in older adults undergoing TAVR and SAVR, which is in turn associated with a higher risk for mid-term mortality.

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).

Cost of Cardiac Surgery in Frail Compared With Nonfrail Older Adults.

BACKGROUND: Frailty is a risk factor for mortality, morbidity, and prolonged length of stay after cardiac surgery, all of which are major drivers of hospitalization costs. The incremental hospitalization costs incurred in frail patients have yet to be elucidated. METHODS: Patients aged ≥ 60 years were evaluated for frailty before coronary artery bypass grafting or heart valve surgery at 2 academic centres between 2013 and 2015 as part of the McGill Frailty Registry. Total costs were summed from the date of the index surgery to the date of hospital discharge. Mutivariable linear regression was used to determine the association between preoperative frailty status and total costs after adjusting for conventional surgical risk factors. RESULTS: Among 235 patients included in the analysis, the median age was 73.0 years (interquartile range [IQR], 70.0-78.0 years) and 68 (29%) were women. The median cost was $32,742 (IQR, $23,221-$49,627) in 91 frail patients compared with $23,370 (IQR, $19,977-$29,705) in 144 nonfrail patients. Seven extreme-cost cases > $100,000 were identified, and all of the patients in these cases exhibited baseline frailty. In the multivariable model, total costs were independently associated with frailty (adjusted additional cost, $21,245; 95% confidence interval [CI], $12,418-$30,073; P < 0.001) and valve surgery (adjusted additional cost, $20,600; 95% CI, $9,661-$31,539; P < 0.001). CONCLUSIONS: Frailty is associated with a marked increase in hospitalization costs after cardiac surgery, an effect that persists after adjusting for age, sex, surgery type, and surgical risk score. Further efforts are needed to optimize care and resource use in this vulnerable population.

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.

Derivation and Validation of Prognosis-Based Age Cutoffs to Define Elderly in Cardiac Surgery.

BACKGROUND: The age cutoff to define elderly is controversial in cardiac surgery, empirically ranging from ≥65 to ≥80 years. Beyond semantics, this has important implications as a starting point for clinical care pathways and inclusion in trials. We sought to characterize the relationship between age and adverse outcomes in patients undergoing cardiac surgery and to derive and validate prognosis-based age cutoffs. METHODS AND RESULTS: Six thousand five hundred seventy one consecutive adult patients undergoing cardiac surgery at 3 hospitals in the United States and Canada were included in the cohort. Logistic regression models and generalized additive models with thin-plate splines were fit to the data. The age distribution was 50 to 59 years in 1244 (18.9%), 60 to 69 years in 2144 (32.6%), 70 to 79 years in 2000 (30.4%), ≥80 years in 1183 (18.0%) patients. After controlling for sex and type of operation, the relationship between age and 30-day operative mortality was found to be nonlinear. Receiver operating characteristic analysis showed that the optimal cutoffs to identify older patients at higher risk of operative mortality were greater than 74, 78, and 75 years for isolated coronary bypass, isolated valve surgery, and coronary bypass plus valve surgery, respectively. These age cutoffs were validated in an independent cohort. CONCLUSIONS: The relationship between age and operative mortality is not linear, manifesting a steeper rise after age 75 for coronary bypass and approaching octogenarian age for isolated valve surgery. Rather than using arbitrary age cutoffs to define elderly, the outcomes-based cutoff of ≥75 years should be used to identify the population of older adults that has higher risk and may benefit from preoperative geriatric evaluation and optimization.

Effect of Pre-Operative Use of Medications on the Risk of Surgical Site Infections in Patients Undergoing Cardiac Surgery.

BACKGROUND: Median sternotomy, the most common means of accessing the heart for cardiac procedures, is associated with higher risk of surgical site infections (SSIs). A limited number of studies reporting the impact of medication use prior to cardiac surgery on the subsequent risk of SSIs usually focused on antibacterial prophylaxis. The objective of the current study was to evaluate the effect of medications prescribed commonly to cardiac patients on the risk of incident SSIs. METHODS: The study analyzed data on consecutive cardiac surgery patients undergoing median sternotomy at a McGill University teaching hospital between April 1, 2011 and October 31, 2013. Exposure of interest was use of medications for heart disease and cardiovascular conditions in the seven days prior to surgery and those for comorbid conditions. The main outcome was SSIs occurring within 90 d after surgery. Univariate and multivariate logistic regression (adjusted odds ratio [AOR]) was used to evaluate the effect. RESULTS: The cohort included 1,077 cardiac surgery patients, 79 of whom experienced SSIs within 90 d of surgery. The rates for sternal site infections and harvest site infections were 5.8 (95% confidence interval [CI]: 4.4-7.3) and 2.5 (95% CI: 1.4-3.7) per 100 procedures, respectively. The risk of SSI was increased with the pre-operative use of immunosuppressors/steroids (AOR 3.47, 95% CI: 1.27-9.52) and α-blockers (AOR 3.74, 95% CI: 1.21-1.47). CONCLUSIONS: Our findings support the effect of immunosuppressors/steroids on the risk of SSIs and add evidence to the previously reported association between the use of anti-hypertensive medications and subsequent development of infection/sepsis.

Outcome Reporting in Cardiac Surgery Trials: Systematic Review and Critical Appraisal.

BACKGROUND: There is currently no accepted standard for reporting outcomes following cardiac surgery. The objective of this paper was to systematically review the literature to evaluate the current use and definition of perioperative outcomes reported in cardiac surgery trials. METHODS AND RESULTS: We reviewed 5 prominent medical and surgical journals on Medline from January 1, 2010, to June 30, 2014, for randomized controlled trials involving coronary artery bypass grafting and/or valve surgery. We identified 34 trials meeting inclusion criteria. Sample sizes ranged from 57 to 4752 participants (median 351). Composite end points were used as a primary outcome in 56% (n=19) of the randomized controlled trials and as a secondary outcome in 12% (n=4). There were 14 different composite end points. Mortality at any time (all-cause and/or cardiovascular) was reported as an individual end point or as part of a combined end point in 82% (n=28), myocardial infarction was reported in 68% (n=23), and bleeding was reported in 24% (n=8). Patient-centered outcomes, such as quality of life and functional classification, were reported in 29% (n=10). Definition of clinical events such as myocardial infarction, stroke, renal failure, and bleeding varied considerably among trials, particularly for postoperative myocardial infarction and bleeding, for which 8 different definitions were used for each. CONCLUSIONS: Outcome reporting in the cardiac surgery literature is heterogeneous, and efforts should be made to standardize the outcomes reported and the definitions used to ascertain them. The development of standardizing outcome reporting is an essential step toward strengthening the process of evidence-based care in cardiac surgery.

Preoperative anxiety as a predictor of mortality and major morbidity in patients aged >70 years undergoing cardiac surgery.

The present study examined the association between patient-reported anxiety and postcardiac surgery mortality and major morbidity. Frailty Assessment Before Cardiac Surgery was a prospective multicenter cohort study of elderly patients undergoing cardiac surgery (coronary artery bypass surgery and/or valve repair or replacement) at 4 tertiary care hospitals from 2008 to 2009. The patients were evaluated a mean of 2 days preoperatively with the Hospital Anxiety and Depression Scale, a validated questionnaire assessing depression and anxiety in hospitalized patients. The primary predictor variable was a high level of anxiety, defined by a Hospital Anxiety and Depression Scale score of ≥ 11. The main outcome measure was all-cause mortality or major morbidity (e.g., stroke, renal failure, prolonged ventilation, deep sternal wound infection, or reoperation) occurring during the index hospitalization. Multivariable logistic regression analysis examined the association between high preoperative anxiety and all-cause mortality/major morbidity, adjusting for the Society of Thoracic Surgeons predicted risk, age, gender, and depression symptoms. A total of 148 patients (mean age 75.8 ± 4.4 years; 34% women) completed the Hospital Anxiety and Depression Scale. High levels of preoperative anxiety were present in 7% of patients. No differences were found in the type of surgery and Society of Thoracic Surgeons predicted risk across the preoperative levels of anxiety. After adjusting for potential confounders, high preoperative anxiety was remained independently predictive of postoperative mortality or major morbidity (odds ratio 5.1, 95% confidence interval 1.3 to 20.2; p = 0.02). In conclusion, although high levels of anxiety were present in few patients anticipating cardiac surgery, this conferred a strong and independent heightened risk of mortality or major morbidity.

The Canadian Society of Cardiac Surgeons perspective on the cardiac surgery workforce in Canada.

As the professional society representing cardiac surgeons in Canada, the Canadian Society of Cardiac Surgeons (CSCS) recognizes the importance of maintaining a stable cardiac surgical workforce. The current reactive approach to health human resource management in cardiac surgery is inadequate and may result in significant misalignment of cardiac surgeon supply and demand. The availability of forecasting models and high quality, consistent data on productivity, workload, utilization, and demand is a prerequisite for our profession's capacity to predict and plan for changes in health human resources. The CSCS recognizes that improved workforce management is a key component to providing optimal cardiac surgical care for Canadians in the future and has developed the recommendations in this document as a call to action to interested stakeholders and policymakers to bring substantial improvements to health human resource management in cardiac surgery.

Addition of frailty and disability to cardiac surgery risk scores identifies elderly patients at high risk of mortality or major morbidity.

Background- Cardiac surgery risk scores perform poorly in elderly patients, in part because they do not take into account frailty and disability which are critical determinants of health status with advanced age. There is an unmet need to combine established cardiac surgery risk scores with measures of frailty and disability to provide a more complete model for risk prediction in elderly patients undergoing cardiac surgery. Methods and Results- This was a prospective, multicenter cohort study of elderly patients (≥70 years) undergoing coronary artery bypass and/or valve surgery in the United States and Canada. Four different frailty scales, 3 disability scales, and 5 cardiac surgery risk scores were measured in all patients. The primary outcome was the STS composite end point of in-hospital postoperative mortality or major morbidity. A total of 152 patients were enrolled, with a mean age of 75.9±4.4 years and 34% women. Depending on the scale used, 20-46% of patients were found to be frail, and 5-76% were found to have at least 1 disability. The most predictive scale in each domain was: 5-meter gait speed ≥6 seconds as a measure of frailty (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.17-5.90), ≥3 impairments in the Nagi scale as a measure of disability (OR, 2.98; 95% CI, 1.35-6.56) and either the Parsonnet score (OR, 1.08; 95% CI, 1.04-1.13) or Society of Thoracic Surgeons Predicted Risk of Mortality or Major Morbidity (STS-PROMM) (OR, 1.05; 95% CI, 1.01-1.09) as a cardiac surgery risk score. Compared with the Parsonnet score or STS-PROMM alone, (area under the curve, 0.68-0.72), addition of frailty and disability provided incremental value and improved model discrimination (area under the curve, 0.73-0.76). Conclusions- Clinicians should use an integrative approach combining frailty, disability, and risk scores to better characterize elderly patients referred for cardiac surgery and identify those that are at increased risk.

Gait speed as an incremental predictor of mortality and major morbidity in elderly patients undergoing cardiac surgery.

OBJECTIVES: The purpose of this study was to test the value of gait speed, a clinical marker for frailty, to improve the prediction of mortality and major morbidity in elderly patients undergoing cardiac surgery. BACKGROUND: It is increasingly difficult to predict the elderly patient's risk posed by cardiac surgery because existing risk assessment tools are incomplete. METHODS: A multicenter prospective cohort of elderly patients undergoing cardiac surgery was assembled at 4 tertiary care hospitals between 2008 and 2009. Patients were eligible if they were 70 years of age or older and were scheduled for coronary artery bypass and/or valve replacement or repair. The primary predictor was slow gait speed, defined as a time taken to walk 5 m of ≥ 6 s. The primary end point was a composite of in-hospital post-operative mortality or major morbidity. RESULTS: The cohort consisted of 131 patients with a mean age of 75.8 ± 4.4 years; 34% were female patients. Sixty patients (46%) were classified as slow walkers before cardiac surgery. Slow walkers were more likely to be female (43% vs. 25%, p = 0.03) and diabetic (50% vs. 28%, p = 0.01). Thirty patients (23%) experienced the primary composite end point of mortality or major morbidity after cardiac surgery. Slow gait speed was an independent predictor of the composite end point after adjusting for the Society of Thoracic Surgeons risk score (odds ratio: 3.05; 95% confidence interval: 1.23 to 7.54). CONCLUSIONS: Gait speed is a simple and effective test that may identify a subset of vulnerable elderly patients at incrementally higher risk of mortality and major morbidity after cardiac surgery.

Clinical relevance of ventilation during cardiopulmonary bypass in the prevention of postoperative lung dysfunction.

The current clinical study is the continuity of previous experimental findings in which ventilation during cardiopulmonary bypass (CPB) prevented reperfusion injury of the pulmonary arterial tree as demonstrated by preservation of vasorelaxation to acetylcholine (ACh) in swine. The aim of this prospective randomized study is to determine: 1) if ventilation during CPB prevents the selective endothelium-mediated lung dysfunction in humans and, 2) the clinical relevance of ventilation during CPB. Forty patients scheduled for primary coronary artery bypass grafting (CABG) were randomized into two groups: Group 1: Usual care (defined as no ventilation during CPB) and Group 2: CPB with low tidal volume ventilation (3 ml.kg(-1)) without positive end expiratory pressure (PEEP). To evaluate endothelial function, ACh was injected into the pulmonary artery and the changes in pulmonary vascular resistance index (PVRI) were measured at: (1) induction of anesthesia prior to surgery, (2) immediately after weaning from CPB and (3) 1 hour after CPB. In addition, secondary endpoints, such as PaO(2)/FiO(2) ratio, mean pulmonary artery pressure (MPAP), postoperative length of stay (LOS) and postoperative pulmonary complications were measured to evaluate the effect of ventilation during CPB. To assess pulmonary complications, a chest x-ray was taken on the first and third postoperative days. There were no statistically significant changes in PVRI, PaO(2) /FiO(2) ratio, MPAP, postoperative LOS and postoperative pulmonary complications when comparing the non-ventilated and the ventilated groups during CPB. The ventilated group appears to obtain a greater vasorelaxation to ACh, as shown by the more pronounced change in PVRI when compared to the non-ventilated group. However, the difference in PVRI between the two groups was not statistically significant after weaning (p= 0.32) and 1hr after CPB (p= 0.28). Contrary to our hypothesis and due to larger than expected variability in the data, the hemodynamic and clinical changes seen were not statistically significant.

Enantioselective total synthesis of pyrinodemin A.

Pyrinodemin A 1, a cytotoxic marine alkaloid, was synthesized in a convergent and enantioselective fashion. The key steps are an asymmetric intramolecular dipolar cycloaddition of an oxazoline N-oxide to introduce the bicyclic ring system of the molecule, a cuprate coupling for the extension of the saturated chain and a B-alkyl Suzuki coupling for the introduction of a 3-pyridyl moiety. Reductive amination allowed the coupling of the second side-chain onto the nitrogen atom to give 1. Additionally, attempts to prepare 1 from a trienic precursor by a double B-alkyl Suzuki reaction are described.