Stevens, Susanna R.

Background and Objectives: Patients undergoing major orthopedic surgery experience significant postoperative pain. Failure to provide adequate analgesia may impede early physical therapy and rehabilitation, which are important factors for maintaining joint range of motion and facilitating hospital dismissal. We examined the effect of a pre-emptive, multimodal, perioperative analgesic regimen emphasizing peripheral nerve block in patients undergoing total hip (THA) and total knee (TKA) arthroplasty. Perioperative outcomes and major postoperative complications were evaluated. Methods: One hundred consecutive patients undergoing primary or revision THA or TKA using the Mayo Clinic Total Joint Regional Anesthesia (TJRA) protocol were retrospectively reviewed. The TJRA protocol is a pre-emptive, multimodal, perioperative analgesic regimen emphasizing peripheral nerve block that was jointly developed by the Departments of Anesthesiology and Orthopedic Surgery. Identified patients were matched 1:1 with historical controls undergoing identical surgical procedures with traditional anesthetic techniques. Matching criteria included patient age, gender, surgeon, date of surgery, and American Society of Anesthesiologists physical status. Patient demographics, preoperative joint range of motion, and anesthetic management were recorded for each patient. The primary study outcome was hospital length of stay. Secondary outcome variables included time to ambulation, joint range of motion, and discharge eligibility. Postoperative verbal analog pain scores (VAS), opioid requirements, side effects, and perioperative complications were also documented. Results: One hundred patients underwent THA or TKA using the newly implemented Mayo Clinic TJRA protocol. Matched controls (n = 100) received intravenous patient-controlled analgesia with subsequent conversion to oral analgesics for postoperative pain management. TJRA patients had significantly shorter hospital lengths of stay (3.8 days v 5.0 days; P < .001), achieved discharge eligibility significantly sooner (1.7 ± 1.9 days earlier; P < .0001), and had improved joint range of motion (90° v 85°; P = .008) when compared with matched controls. TJRA patients had significantly improved postoperative analgesia, including lower VAS pain scores (postoperative day 0 through postoperative day 3; P < .001), and lower opioid requirements (postoperative day 0 to postoperative day 2; P = .04). Adverse outcomes such as postoperative urinary retention (50% v 31%; P < .001), and ileus formation (7% v 1%; P = .01) occurred more frequently among control patients. Conclusions: Patients undergoing THA or TKA using a comprehensive, pre-emptive, multimodal analgesic regimen emphasizing peripheral nerve block may have significantly improved perioperative outcomes, and fewer adverse events, when compared with patients receiving traditional intravenous opioids during the initial postoperative period. Improved perioperative outcomes include a shortened hospital length of stay, and a significant reduction in postoperative urinary retention and ileus formation.

Introduction: Insulin-like growth factor-binding protein 7 (IGFBP7) was previously found to be associated with diastolic function in heart failure (HF) with reduced ejection fraction (EF), but it is unclear whether such associations exist in HF with preserved EF (HFpEF), where diastolic function is of pivotal importance. Hypotheses: Baseline (BL) and change (Δ) in IGFBP7 will be significantly associated and correlated with BL and Δ in diastolic indices as well as peak oxygen consumption (VO2 max ) in patients with HFpEF. IGFBP7 will decrease with sildenafil therapy. Methods: At BL and 6 months (6M), IGFBP7, imaging studies, and VO2 max were obtained and compared in 160 HFpEF patients randomized to sildenafil or placebo. Results: Patients with supramedian BL IGFBP7 concentrations (>219 ng/mL) were more likely to be older, to have more congestion and worse renal function, and to have elevated concentrations of several emerging or established HF biomarkers including amino-terminal pro-B-type natriuretic peptide, cystatin C, and highly sensitive troponin (all P<0.05). Higher BL IGFBP7 was correlated with indices of worse diastolic function, including higher E velocity (ρ=0.395, P<0.001), E/e’ (ρ=0.398, P<0.001), left atrial volume index (ρ=0.386, P<0.001), right ventricular systolic pressure (RVSP; ρ=0.413, P<0.001), and transmitral E/A (ρ=0.258, P=0.006). IGFBP7 was also inversely correlated with aortic distensability (ρ= -0.301, P=0.02). There was no association or correlation with measures of systolic function. Notably, in analyses adjusted for respective baseline variables, ΔIGFBP7 was significantly correlated with Δ in E (ρ=0.114), E/A (ρ=0.225), E/e’ (ρ=0.174), and RVSP (ρ=0.282; all P<0.03). Elevated BL IGFBP7 was associated with lower BL VO2 max (13.2 versus 11.1 mL/min/kg; P<0.001) and ΔIGFBP7 was inversely correlated with ΔVO2 max (ρ=-0.19, P=0.01). Subjects receiving sildenafil had a decrease in IGFBP7 over 6M in contrast to placebo-treated patients (median ΔIGFBP7 -1.5 versus +13.6 ng/mL; P<0.001). Conclusions: In patients with HFpEF, concentrations of IGFBP7 have unique relationships with measures of diastolic dysfunction and VO2 max . Rise in IGFBP7 may reflect worsening diastology and deteriorating VO2 max .

Introduction: In vitro, ST2 is a marker of myocyte stress and inflammation but in vivo, there is no trans-cardiac ST2 concentration step-up to support cardiac ST2 activation in human heart failure (HF) calling into question the source of ST2 in HF. While ST2 is predictive of adverse outcomes in HF, the relationship between ST2 and key pathophysiologic domains in HF with preserved ejection fraction (HFpEF) is not well characterized. Hypothesis: ST2 levels increase in proportion to the severity of left ventricular (LV) remodeling and dysfunction in HFpEF. Methods: At enrollment, patients (n=174) from the RELAX trial testing sildenafil in HFpEF had serum ST2 levels measured and underwent assessment of pathophysiologic domains including congestion, cardiac structure and function, exercise performance (peak oxygen consumption (VO2)) and biomarkers of neurohumoral activation (NT-proBNP, aldosterone, endothelin-1), renal dysfunction (cystatin-C), fibrosis (pro-collagen III N-terminal peptide [NTP], C-telopeptide for type I collagen [CITP]), inflammation (high-sensitivity CRP [hsCRP]) and myocardial necrosis (high-sensitivity troponin-I [hsTnI]). Analysis adjusted for sex, a covariate associated with ST2 levels in normal persons. Results: See table. ST2 was associated with greater congestion, worse right ventricular (RV) pressure overload and dysfunction, lower peak VO2 and biomarkers of neurohumoral activation, renal dysfunction, fibrosis and myocardial necrosis and tended to be associated with systemic inflammation (hsCRP). ST2 was not associated with LV structure or LV systolic or diastolic function. Conclusions: In HFpEF, ST2 was associated with measures of right sided congestion, RV overload and dysfunction, exercise intolerance and other systemic markers of more advanced HF but not with LV structure or LV systolic or diastolic function. These data suggest that mechanisms distinct from LV stress stimulate ST2 activation in HFpEF.

Background: Among patients (pts) with coronary artery disease (CAD) who are candidates for coronary artery bypass graft surgery (CABG), a reduced ejection fraction (EF) identifies a high-risk group. The profile of pre-operative, intra-operative and post-operative factors contributing to 30 day (d) mortality in pts with low EF undergoing CABG has not been well characterized. Methods: The STICH trial enrolled 2136 pts with CAD amenable to CABG with an LVEF < 35% who were treated with medical therapy (MED) alone, MED with CABG, or with MED plus CABG and surgical ventricular resconstruction (SVR). Multivariable logistic regression models utilizing extensive baseline, intra-operative and post-operative care variables were developed to determine factors associated with mortality at 30d in a landmark analysis among pts surviving the first 36 hours (h). Results: Among those enrolled, 1460 pts received CABG; 673 (46.1%) on pump, 160 (11.0%) off pump, 132 (9.0%) with a mitral valve procedure (MVR), 393 (26.9%) with SVR, and 102 (7.0%) received CABG with SVR and MVR. Mortality in the operating room (OR) was 0.3 %, within the first 36h was 1.0%, and at 30d was 5.1%. The rate of in-hospital acute myocardial infarction was 0.8%, stroke 1.6%, mediastinitis 1.7%, worsening renal insufficiency 8.4%, and return to OR was 6.9%. Inotropes were used in 43.6% and intra-aortic balloon pump in 18.6%. At 36h, 148 pts (10.2%) remained intubated. Among pts who survived to 36h, a robust multivariable model (Table, c-statistic 0.89) was developed to predict 30d mortality. A prolonged intubation time (>36h) was the strongest marker of 30d mortality (odds ratio 7.4, 95% CI 3.8, 14.5, p<0.0001). Conclusions: Among pts with ischemic heart failure, CABG can be performed with a low rate of complications and intra-operative mortality. Prolonged intubation time (>36h) after CABG is an integrated clincal marker that may serve to identify those pts with the least likelihood of survival to 30d.

Background: The Acute Decompensated Heart Failure National Registry (ADHERE) risk levels are a validated tool to assess the risk of in-hospital mortality in patients with acute decompensated heart failure (ADHF). The objective of this study is to determine if the risk levels predict 60-day outcomes in well-defined ADHF patients from NIH Heart Failure Clinical Research Network (HFCRN) trials. Methods: Our study cohort included 835 unique patients with ADHF enrolled in 3 NIH HFCRN trials: Diuretic Optimization Strategies Evaluation (DOSE), CARdiorenal REScue Study in Acute Decompensated Heart Failure (CARRESS-HF), and Renal Optimization Strategies Evaluation (ROSE). ADHERE risk level was assigned, as previously described, by baseline BUN (<43 vs. ≥43 mg/dL), Cr (<2.2 vs. ≥2.2, a modification from 2.75 mg/dL used in ADHERE due the Cr distribution in our study population), and systolic BP (≥ 115 vs < 115 mmHg). Baseline characteristics and outcomes were compared between risk levels. Results: Of the 835 patients enrolled in DOSE (308), CARRESS-HF (188), and ROSE (360), an ADHERE risk level could be assigned to 830, with 62 (8%) high, 521 (63%) intermediate, 247 (30%) low risk. Baseline characteristics (Table 1) and outcomes (Table 2), including combined 60-day death and re-hospitalization (hazard ratio 1.94, high risk versus low risk, p<0.01), varied by ADHERE risk level. Conclusion: ADHERE risk levels predict 60-day death and re-hospitalization rates in patients with ADHF. These results extend the utility of the ADHERE risk levels, by informing longer-term clinical decisions regarding advanced heart failure treatment, care transition strategies and clinical trial design.

Recent findings suggest that compromised patient effort occurs in nonlitigious settings, but the nature and base rate of suboptimal effort in these settings remains poorly understood. In the treatment-seeking, acquired brain injury, outpatient rehabilitation sample included in this investigation, 21.8% of the patients scored below recommended cutting scores for suboptimal effort on the Test of Memory Malingering (TOMM). Disability status was the only variable explored in this study to be associated with suboptimal effort. It should be noted, however, that the proportion of patients on disability was large in both the optimal and suboptimal effort groups, suggesting that failure on the TOMM may not be a specific predictor of disability status in this sample. Importantly, performance on the TOMM was unrelated to age, education, time from injury to evaluation, and injury severity. Depression and anxiety were also shown to be unrelated to TOMM performance in this rehabilitation sample. As expected, performance on neurocognitive testing was significantly lower in the suboptimal effort group. This study suggests that reduced effort occurs outside forensic settings, is related to neuropsychometric performance, and urges further research into effort across various settings.

Objectives To define the prognostic contribution of global and regional left ventricular (LV) function measurements in patients with ischaemic cardiomyopathy randomised to coronary artery bypass graft surgery (CABG) with (n=501) or without (n=499) surgical ventricular reconstruction (SVR). Methods Novel multivariable methods to analyse global and regional LV systolic function were used to better formulate prediction models for long-term mortality following CABG with or without SVR in the entire cohort of 1000 randomised SVR hypothesis patients. Key clinical variables were included in the analysis. Regional function was classified according to the discreteness of anteroapical hypokinesia and akinesia into those most likely to benefit from SVR, those least likely and those felt to have intermediate likelihood of benefit from SVR. Results The most prognostic clinical variables identified in multivariable models include creatinine, LV end-systolic volume index (ESVI), age and NYHA (New York Heart Association) class. Addition of LV ejection fraction, LV end-diastolic volume index and regional function assessment did not contribute additional power to the model. Subgroup analysis based on regional function did not identify a cohort in which SVR improved mortality. Conclusions ESVI is the single parameter of LV function most predictive of mortality in patients with LV systolic dysfunction following CABG with or without SVR in multivariable models that include all key clinical and LV systolic function parameters. Assessment of regional cardiac function does not enhance prediction of mortality nor identify a subgroup for which SVR improves mortality. These results do not support elective addition of LV reconstruction surgery in patients undergoing CABG. Trial registration number NCT00023595.

Background Soluble ST2 is a biomarker that is elevated in certain systemic inflammatory diseases. Comorbidity‐driven microvascular inflammation is postulated to play a key role in heart failure with preserved ejection fraction ( HF p EF ) pathophysiology, but data on how sST 2 relates to clinical characteristics or inflammatory conditions or biomarkers in HF p EF are limited. We sought to determine circulating levels and clinical correlates of sST 2 in HF pEF. Methods and Results At enrollment, patients (n=174) from the Phosphodiesterase‐5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Heart Failure (RELAX) trial of sildenafil in HF p EF had sST 2 levels measured. Clinical characteristics; cardiac structure and function; exercise performance; and biomarkers of neurohumoral activation, systemic inflammation and fibrosis, and myocardial necrosis were assessed in relation to sST 2 levels. Median sST 2 levels in male and female HFpEF patients were 36.7 ng/mL (range 30.9–49.2 ng/mL; reference range 4–31 ng/mL) and 30.8 ng/mL (range 25.3–39.3 ng/mL; reference range 2–21 ng/mL), respectively. Among HF p EF patients, higher sST 2 levels were associated with the presence of diabetes mellitus; atrial fibrillation; renal dysfunction; right ventricular pressure overload and dysfunction; systemic congestion; exercise intolerance; and biomarkers of systemic inflammation and fibrosis, neurohumoral activation, and myocardial necrosis ( P <0.05 for all). sST 2 was not associated with left ventricular structure or left ventricular systolic or diastolic function. Conclusions In HF p EF , sST 2 levels were associated with proinflammatory comorbidities, right ventricular pressure overload and dysfunction, and systemic congestion but not with left ventricular geometry or function. These data suggest that sST2 may be a marker of systemic inflammation in HF p EF and potentially of extracardiac origin. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00763867.

Background— The ROSE AHF trial (Renal Optimization Strategies Evaluation in Acute Heart Failure) found that when compared with placebo, neither low-dose dopamine (2 µg/kg per minute) nor low-dose nesiritide (0.005 μg/kg per minute without bolus) enhanced decongestion or preserved renal function in AHF patients with renal dysfunction. However, there may be differential responses to vasoactive agents in AHF patients with reduced versus preserved ejection fraction (EF). This post hoc analysis examined potential interaction between treatment effect and EF (EF ≤40% versus >40%) on the ROSE AHF end points. Methods and Results— ROSE AHF enrolled AHF patients (n=360; any EF) with renal dysfunction. The coprimary end points were cumulative urine volume and the change in serum cystatin-C in 72 hours. The effect of dopamine (interaction P =0.001) and nesiritide (interaction P =0.039) on urine volume varied by EF group. In heart failure with reduced EF, urine volume was higher with active treatment versus placebo, whereas in heart failure with preserved EF, urine volume was lower with active treatment. The effect of dopamine and nesiritide on weight change, sodium excretion, and incidence of AHF treatment failure also varied by EF group (interaction P <0.05 for all). There was no interaction between vasoactive treatment’s effect and EF on change in cystatin-C. Compared with placebo, dopamine was associated with improved clinical outcomes in heart failure with reduced EF and worse clinical outcomes in heart failure with preserved EF. With nesiritide, there were no differences in clinical outcomes when compared with placebo in both heart failure with reduced EF and heart failure with preserved EF. Conclusions— In this post hoc analysis of ROSE AHF, the response to vasoactive therapies differed in patients with heart failure with reduced EF and heart failure with preserved EF. Investigations of AHF therapies should assess the potential for differential responses in AHF with preserved versus reduced EF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01132846.

This prospective, observational pilot study was conducted on an academic inpatient rehabilitation unit. Ninety-three persons with spinal cord dysfunction or severe neurological illness participated. All completed admission surveys; 46 completed surveys six months after discharge. The aims were to describe admission and post-discharge spirituality and associations between spirituality and rehabilitation outcomes. At admission, participants reported spirituality similar to that of other samples of medical patients. After discharge, frequency of private spiritual practices increased and spiritual and existential well-being decreased. No significant associations were detected between spirituality and rehabilitation outcomes. Findings suggest the importance of spirituality to the participants and future research with a larger sample and modifications to the methodology.