Tina Harding

Identifying frailty in hospitalized older adults with significant coronary artery disease

OBJECTIVES: To characterize physiological variation in hospitalized older adults with severe coronary artery disease (CAD) and evaluate the prevalence of frailty in this sample, to determine whether single‐item performance measures are good indicators of multidimensional frailty, and to estimate the association between frailty and 6‐month mortality.

Early Surgery in Patients with Infective Endocarditis: A Propensity Score Analysis

BACKGROUND An accurate assessment of the predictors of long-term mortality in patients with infective endocarditis is not possible using retrospective data because of inherent treatment biases and predictable imbalances in the distribution of prognostic factors. Largely because of these limitations, the role of surgery in long-term survival has not been adequately studied. METHODS Data were collected prospectively from 426 patients with infective endocarditis. Variables associated with surgery in patients who did not have intracardiac devices who had left-side-associated valvular infections were determined using multivariable analysis. Propensity scores were then assigned to each patient based on the likelihood of undergoing surgery. Using individual propensity scores, 51 patients who received medical and surgical treatment were matched with 51 patients who received medical treatment only. RESULTS The following factors were statistically associated with surgical therapy: age, transfer from an outside hospital, evidence of infective endocarditis on physical examination, the presence of infection with staphylococci, congestive heart failure, intracardiac abscess, and undergoing hemodialysis without a chronic catheter. After adjusting for surgical selection bias by propensity score matching, regression analysis of the matched cohorts revealed that surgery was associated with decreased mortality (hazard ratio, 0.27; 95% confidence interval, 0.13-0.55). A history of diabetes mellitus (hazard ratio, 4.81; 95% confidence interval, 2.41-9.62), the presence of chronic intravenous catheters at the beginning of the episode (hazard ratio, 2.65; 95% confidence interval, 1.31-5.33), and paravalvular complications (hazard ratio, 2.16; 95% confidence interval, 1.06-4.44) were independently associated with increased mortality. CONCLUSIONS Differences between clinical characteristics of patients with infective endocarditis who receive medical therapy versus patients who receive surgical and medical therapy are paramount. After controlling for inherent treatment selection bias and imbalances in prognostic factors using propensity score methodology, risk factors associated with increased long-term mortality included diabetes mellitus, the presence of a chronic catheter at the onset of infection, and paravalvular complications. In contrast, surgical therapy was associated with a significant long-term survival benefit.

Frequency and Predictors of Drug-Eluting Stent Use in Saphenous Vein Bypass Graft Percutaneous Coronary Interventions : A Report From the American College of Cardiology National Cardiovascular Data CathPCI Registry

OBJECTIVES We examined a large registry to determine the frequency and factors associated with drug-eluting stents (DES) use in saphenous vein graft (SVG) in contemporary practice. BACKGROUND Prospective trials comparing DES with bare-metal stents in SVG lesions have provided conflicting conclusions regarding safety and efficacy leading to potential variation in stent choice for these lesions. METHODS We analyzed the frequency and factors associated with DES use in patients undergoing SVG stenting from January 1, 2004, to March 31, 2009, in the National Cardiovascular Data Registry. Generalized estimating equations logistic regression modeling was used to generate independent variables associated with DES use in SVGs. RESULTS During the study period, percutaneous coronary intervention (PCI) of a SVG represented 5.7% of the total PCI volume (91,355 of 1,596,966). Of the 84,875 patients who received a SVG stent, a DES was used in 64.5%. From 2005 to 2009, DES use in SVG PCI changed from 80% to 62%. Unfractionated heparin was used in 46%, enoxaparin in 17%, bivalirudin in 42%, and a glycoprotein IIb/IIIa inhibitor in 40% of cases. On multivariable analysis, several parameters (including the period, multivessel PCI, prior PCI, no acute myocardial infarction, and no smoking) were associated with DES use. CONCLUSIONS Currently, DES are used in nearly two-thirds of SVG interventions. Several clinical parameters (such as the period of implantation and the complexity of coronary artery disease) are associated with the decision to implant a DES in these challenging lesions.

The Adherence evaluation After Ischemic Stroke Longitudinal (AVAIL) Registry : Design, rationale, and baseline patient characteristics

BACKGROUND Approximately one third of the 780,000 people in the United States who have a stroke each year have recurrent events. Although efficacious secondary prevention measures are available, levels of adherence to these strategies in patients who have had stroke are largely unknown. Understanding medication-taking behavior in this population is an important step to optimizing the appropriate use of proven secondary preventive therapies and reducing the risk of recurrent stroke. METHODS The Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) registry is a prospective study of adherence to stroke prevention medications from hospital discharge to 1 year in patients admitted with stroke or transient ischemic attack. The primary outcomes are medication usage as determined by patient interviews after 3 and 12 months. Potential patient-, provider-, and system-level barriers to persistence of medication use are also collected. Secondary outcomes include the rates of recurrent stroke or transient ischemic attack, vascular events, and rehospitalization and functional status as measured by the modified Rankin score. RESULTS The AVAIL enrolled about 2,900 subjects from 106 hospitals from July 2006 through July 2008. The 12-month follow-up will be completed in August 2009. CONCLUSIONS The AVAIL registry will document the current state of adherence and persistence to stroke prevention medications among a nationwide sample of patients. These data will be used to design interventions to improve the quality of care post acute hospitalization and reduce the risks of future stroke and cardiovascular events.

Quality of life and economic outcomes with surgical ventricular reconstruction in ischemic heart failure: results from the Surgical Treatment for Ischemic Heart Failure trial.

BACKGROUND Surgical ventricular reconstruction (SVR) is used in conjunction with coronary artery bypass graft surgery (CABG) to improve left ventricular function and clinical outcomes in selected patients with ischemic heart failure. The impact of SVR on quality of life (QOL) and medical costs is unknown. METHODS We compared CABG plus SVR with CABG alone in 1,000 patients with ischemic heart failure, an anterior wall scar, and a left ventricular ejection fraction <or=0.35. In 991 (99% of eligible), we collected a battery of QOL instruments. The principal, prespecified QOL measure was the Kansas City Cardiomyopathy Questionnaire, which evaluates the effects of heart failure symptoms on QOL using a scale from 0 to 100 with higher scores indicating better QOL. Structured QOL interviews were conducted at baseline, 4, 12, 24, and 36 months post randomization and were >or=92% complete. Cost data were collected on 196 (98%) of 200 patients enrolled in the United States. RESULTS Heart-failure-related QOL outcomes did not differ between the 2 treatment strategies out to 3 years (median Kansas City Cardiomyopathy Questionnaire scores for CABG alone and CABG plus SVR, respectively: baseline 53 versus 54, P = .53; 3 years 85 versus 84, P = .89). There were no treatment-related differences in other QOL measures. In the US patients, total index hospitalization costs averaged over

Quality-of-Life Outcomes With Coronary Artery Bypass Graft Surgery in Ischemic Left Ventricular Dysfunction: A Randomized Trial

14,500 higher for CABG plus SVR (P = .004) due primarily to 4.2 extra postoperative, high-intensity care days in the hospital. CONCLUSIONS Addition of SVR to CABG in patients with ischemic heart failure did not improve QOL but significantly increased health care costs.

Staphylococcus aureus bacteremia among patients with health care-associated fever.

Context A randomized, controlled trial of patients with high-risk coronary artery disease and heart failure previously reported no significant difference between medical therapy alone and medical therapy plus coronary artery bypass grafting when the outcome was death from any cause. Contribution This study from the same trial reports that medical therapy plus coronary artery bypass grafting is better than medical therapy alone when the outcome is quality of life. Caution The type of therapy was not concealed from patients or investigators. Implication This is the first study to examine how these therapies affect quality of life in patients who have coronary artery disease and heart failure. The Editors Clinical trials performed during the 1970s and 1980s defined several major coronary artery disease (CAD) subgroups for which coronary artery bypass grafting (CABG) provided incremental survival, angina relief, or both relative to medical therapy. These early trials formed the foundation for current practice patterns and guideline recommendations on the use of CABG (13). However, patients with severe left ventricular dysfunction (ejection fraction 0.35) were not represented. Thus, management decisions for these patients have largely relied on clinical judgment to extrapolate from those trials and a small group of observational studies(4, 5). The challenges in using this evidence to select treatment for contemporary patients is further complicated by the substantial improvement in medical therapies for both CAD and heart failure over those used in the earlier trials. The STICH (Surgical Treatment for Ischemic Heart Failure) trial was funded by the National Heart, Lung, and Blood Institute in 2002 to provide a comprehensive evaluation of the incremental therapeutic benefits of routine CABG over contemporary guideline-based medical therapy in patients with severe systolic dysfunction due to CAD (6). A major prespecified secondary end point of the trial was health-related quality of life (QOL), which is an outcome that complements the major clinical end points by assessing the patients experience of, and satisfaction with, the 2 therapeutic strategies compared (7, 8). Methods Patient Population and Primary Clinical Results To test the STICH trials surgical revascularization hypothesis, we randomly assigned 1212 patients with site-defined left ventricular ejection fraction of 0.35 or less and CAD suitable for revascularization to CABG or medical therapy (6). Rationale, trial design, and complete inclusion and exclusion criteria have been described previously (7). Patients were enrolled at 99 clinical sites in 22 countries between July 2002 and May 2007. All patients provided informed consent, and study protocol was approved by each sites institutional review board or ethics committee. Median follow-up was 56 months. The primary intention-to-treat comparison showed that 35.7% of patients assigned to CABG and 40.5% of those assigned to medical therapy died (primary analysis: unadjusted hazard ratio for all-cause mortality, 0.86 [95% CI, 0.72 to 1.04]; P= 0.123; secondary analysis: adjusted hazard ratio for all-cause mortality, 0.82 [CI, 0.68 to 0.99]; P= 0.039). Patients assigned to CABG had lower rates of the 2 major secondary clinical end points: death from cardiovascular causes (hazard ratio, 0.81; P= 0.050) and the composite of all-cause mortality and hospitalization for cardiovascular causes (hazard ratio, 0.74; P< 0.001). Health-Related QOL Data Collection We collected QOL data using structured interviews at baseline and 4, 12, 24, and 36 months after randomization. Site coordinators were specially trained by the Duke Clinical Research Institute Outcomes Research Group to conduct baseline interviews. The original research plan called for all patients to be enrolled in North America and all English- and Spanish-language follow-up QOL interviews to be completed via telephone by the Duke Clinical Research Institute. The few patients expected to require French-language interviews were to be interviewed by site coordinators. When enrollment was expanded outside of North America, the plan was modified to have those site coordinators do all QOL interviews in the patients native language. For nonEnglish-speaking participants, translations of the QOL instruments were obtained from the instrument developers or a translation service was used to create validated translations. The New York Heart Association (NYHA) class and Canadian Cardiovascular Society (CCS) angina class were collected on the clinical case report form at baseline and each follow-up interval. QOL Measures A battery of validated measures was used to provide a comprehensive but efficient assessment of QOL. The principal prespecified QOL measure was the Kansas City Cardiomyopathy Questionnaire (KCCQ), which is a 23-item instrument that measures the effect of heart failure symptoms on QOL (9). We used 3 scales from the Seattle Angina Questionnaire to assess the effect of angina symptoms on QOL outcomes (10), the Short Form-12 Survey to provide a brief overall generic measure of health status (11), and 5 individual scales from the Short Form-36 Health Survey to provide a more detailed assessment of areas of functioning and well-being from a generic perspective (12). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (13). The Cardiac Self-Efficacy Questionnaire was used to measure patient confidence in controlling disease symptoms and maintaining physical functioning (14). Finally, we used the EuroQol-5D, which is a generic instrument consisting of a 5-dimension single summary health status index and a self-rated visual analogue scale (0 to 100) of current health-related QOL (15). Statistical Analysis All primary comparisons were performed with the treatment group defined according to the intention-to-treat principle. Descriptive statistics included percentages for discrete variables and medians with 25th to 75th percentiles plus means with SDs for continuous variables. The chi-square test was used for discrete variable comparisons. Treatment comparisons of continuous variables were done by using a linear mixed model to account for repeated measures within a patient. The baseline QOL measure was used as one of the repeated measures. In PROC MIXED in SAS, version 9.2 (SAS Institute), the baseline, 4-, 12-, 24-, and 36-month measurements within a patient were fitted using maximum likelihood methods with unstructured covariance matrix (16). At each time point, estimated treatment differences, 95% CIs, and P values were obtained using the model estimates. Finally, the proportion of patients who achieved a clinically important improvement of 5 points or more in KCCQ overall summary scores were compared by treatment group using the chi-square test (17). All analyses were conducted using SAS, version 8 or higher. All reported P values were 2-sided. No adjustment was made in significance levels for multiple comparisons. Benchmarks for clinically significant changes in QOL scores for individual patients were used informally to assess the magnitude of the mean difference between the 2 groups. However, a QOL difference between groups at or exceeding the benchmark was not used as a formal decision rule to define clinical significance. Subgroup Analysis Regional effects were tested as interactions between the 5 regions used in the clinical analyses (Asia, Australia and New Zealand, Europe, North America, and South America) and the KCCQ overall summary score. Other interactions tested from those prespecified in the clinical analysis plan included age, sex, race, current NYHA class, left ventricular ejection fraction, baseline diabetes, CCS angina class, and myocardium viability. Sensitivity Analysis Some QOL data were missing because a small proportion of living patients did not complete a scheduled QOL assessment and a larger proportion of patients died before 1 or more of the scheduled assessments could be done. Almost all cases of missing data among living patients were attributed to administrative reasons rather than their state of health (Supplement 1), which supports the assumption of missing at random and the use of multiple imputation techniques. Supplement 1. Data Collection in the Surgical Treatment of Ischemic Heart Disease (STICH) Trial Quality of Life Substudy The STICH trial had a high overall mortality rate and a treatment-related mortality difference, as noted previously. These deaths produced a nonrandom group of survivors who provided the follow-up QOL data. No consensus exists in the statistical literature about how best to analyze intermediate end points, such as QOL, when death prevents complete data collection. The primary concern this issue raises in a treatment comparison is that a therapy more effective at preventing death may also preserve more patients with poor QOL than the comparison therapy. Thus, when comparing QOL in such a situation using all survivors, the therapy with the worse survival might have an artifactual improvement in QOL measurements. Rubin has proposed that because QOL data that are censored due to death do not exist even in theory and should be regarded as undefined, the most meaningful analysis is to compare QOL for patients in the 2 treatment groups who would have survived with either therapy (18). To accomplish this, we performed a survival average causal effect (SACE) analysis (1821). The SACE estimates of QOL are calculated from weighted averages of the QOL data multiplied by survival probability estimates (from survival models developed in the parent STICH study cohort) specific to the study group. The 95% CIs for the SACE were calculated using 200 repetitions of a nonparametric bootstrap procedure (22). These sensitivity analyses are helpful as supplements to the primary analysis but have their own difficulties, not the least of which are the important but untestable assumptioClinical trials performed during the 1970s and 1980s defined several major coronary artery disease (CAD) subgroups for which coronary artery bypass grafting (CABG) provided incremental survival, angina relief, or both relative to medical therapy, which formed the foundation for current practice patterns and guideline recommendations on the use of CABG (1-3). However, patients with severe left ventricular dysfunction (ejection fraction ≤0.35) were not represented in these early trials. Thus, management decisions for these patients have largely relied on clinical judgment to extrapolate from those trials and a small group of observational studies (4, 5). The challenges in using this evidence to select treatment for contemporary patients is further complicated in that medical therapies for both CAD and heart failure have improved substantially over those used in the earlier trials. The STICH (Surgical Treatment for Ischemic Heart Failure) trial was funded by the National Heart, Lung, and Blood Institute in 2002 to provide a comprehensive evaluation of the incremental therapeutic benefits of routine CABG over contemporary guideline-based medical therapy in patients with severe systolic dysfunction due to CAD (6). A major prespecified secondary end point of the trial was health-related quality of life (QOL), which is an outcome that complements the major clinical end points by assessing the patient’s experience of, and satisfaction with, the 2 therapeutic strategies compared (7, 8).

Changes in beliefs about medications during long-term care for ischemic heart disease

BACKGROUND Although Staphylococcus aureus bacteremia is a common, serious infection, accurately identifying febrile patients with this diagnosis at the time of initial evaluation is difficult. The purpose of this investigation was to define clinical characteristics present at the time of the initial recognition of fever that were associated with the presence of any bloodstream infection and, in particular, with S. aureus bacteremia. METHODS All patients > or =18 years of age with a new episode of health care-associated fever (temperature > or =38 degrees C) and at least one blood culture drawn were eligible for enrollment into this prospective multicenter cohort study. Multivariable analyses were conducted and internally validated scoring systems were developed to categorize the risk of bacteremia. RESULTS Of 1015 patients enrolled, 181 patients (17.8%) had clinically significant bacteremia, including 77 patients (7.6%) with S. aureus bacteremia. Clinical characteristics associated with S. aureus bacteremia were the presence of a hemodialysis graft or shunt (odds ratio [OR] 3.22; 95% confidence interval [CI], 1.85-5.61), chills (OR 2.38; 95% CI, 1.43-3.98), and a history of S. aureus infection (OR 2.68; 95% CI, 1.38-5.20). Peripheral vascular catheters were inversely associated with S. aureus bacteremia (OR 0.42; 95% CI, 0.26-0.69). Clinical characteristics associated with any bloodstream infection were central venous access, chills, history of S. aureus infection, and hemodialysis access. CONCLUSIONS Among patients with health care-associated fever, the presence of easily recognizable clinical characteristics at the time of obtaining the initial blood cultures can help to identify patients at increased risk for any bloodstream infection, in particular for S. aureus bacteremia.

Acute management of stroke patients taking non–vitamin K antagonist oral anticoagulants Addressing Real-world Anticoagulant Management Issues in Stroke (ARAMIS) Registry: Design and rationale

BACKGROUND Beliefs such as self-reported low necessity for medications and high concerns about medications are associated with nonadherence. Changes in these beliefs during long-term care have not previously been studied and were evaluated for purposes of this analysis. METHODS From January 2006 through September 2007, patients at 41 hospitals who met entry criteria for the CRUSADE Quality Improvement Initiative were consented for participation in a longitudinal follow-up survey study called MAINTAIN. The patients completed The Beliefs about Medicines Questionnaire at 3 and 12 months postdischarge to assess necessity and concerns related to heart medications. Internal reliability and construct validity of the survey were evaluated at both time points. Changes in necessity and concern scores from 3 to 12 months were determined, and factors associated with negative changes were explored. RESULTS A total of 812 patients completed both surveys. Internal reliability and construct validity were good. From 3 to 12 months, only 9.2% of patients shifted from a high to low necessity score; however, 20.7% of patients shifted from a low to high concern score. Factors found to be statistically significantly and independently associated with increased concern were the perception that the provider did not listen carefully to the patient (odds ratio [OR] 2.63, 95% CI 1.49-4.76), depression at 12 months (OR 2.95, 95% CI 1.57-5.55), hospital discharge with > or =7 medications (OR 1.71, 95% CI 1.07-2.74), and not receiving a medication list/instructions at hospital discharge (OR 1.69, 95% CI 1.05, 2.78). Factors associated with decreased necessity included not having a cardiologist (OR 2.26, 95% CI 1.34-3.83) and nonpersistence at 12 months with lipid-lowering medication (OR 1.85, 95% CI 1.01-3.45). CONCLUSIONS One third of the patients reported a negative change in their beliefs about heart medications. Although some changes were observed in perceived necessity, negative changes in concerns occurred in 1 of every 5 patients. Interventions that address these concerns may be useful in improving adherence and clinical outcomes.

Quality-of-Life Outcomes With Coronary Artery Bypass Graft Surgery in Ischemic Left Ventricular DysfunctionA Randomized TrialQuality-of-Life Outcomes in Surgical Treatment of Ischemic Heart Failure

BACKGROUND Non-vitamin K antagonist oral anticoagulants (NOACs, dabigatran, rivaroxaban, apixaban, and edoxaban) have been increasingly used as alternatives to warfarin for stroke prophylaxis in patients with atrial fibrillation. Yet there is substantial lack of information on how patients on NOACs are currently treated when they have an acute ischemic stroke and the best strategies for treating intracerebral hemorrhage for those on chronic anticoagulation with warfarin or a NOAC. These are critical unmet needs for real world clinical decision making in these emergent patients. METHODS The ARAMIS Registry is a multicenter cohort study of acute stroke patients who were taking chronic anticoagulation therapy prior to admission and are admitted with either an acute ischemic stroke or intracerebral hemorrhage. Built upon the existing infrastructure of American Heart Association/American Stroke Association Get With the Guidelines Stroke, the ARAMIS Registry will enroll a total of approximately 10,000 patients (5000 with acute ischemic stroke who are taking a NOAC and 5000 with anticoagulation-related intracerebral hemorrhage who are on warfarin or a NOAC). The primary goals of the ARAMIS Registry are to provide a comprehensive picture of current treatment patterns and outcomes of acute ischemic stroke patients on NOACs, as well as anticoagulation-related intracerebral hemorrhage in patients on either warfarin or NOACs. Beyond characterizing the index hospitalization, up to 2500 patients (1250 ischemic stroke and 1250 intracerebral hemorrhage) who survive to discharge will be enrolled in an optional follow-up sub-study and interviewed at 3 and 6 months after discharge to assess longitudinal medication use, downstream care, functional status, and patient-reported outcomes. CONCLUSION The ARAMIS Registry will document the current state of management of NOAC treated patients with acute ischemic stroke as well as contemporary care and outcome of anticoagulation-related intracerebral hemorrhage. These data will be used to better understand optimal strategies to care for these complex but increasingly common emergent real world clinical challenges.