Impact of Spironolactone on Longitudinal Changes in Health-Related Quality of Life in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial.

BACKGROUND: Heart failure (HF) with preserved ejection fraction patients have equally impaired health-related quality of life (HRQL) compared with those with HF with reduced ejection fraction, but limited studies have evaluated the impact of therapies on changes in HRQL. METHODS AND RESULTS: Patients ≥50 years of age, with symptomatic HF and left ventricular ejection fraction ≥45%, were enrolled in Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) and randomized to spironolactone or placebo. Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), which was the primary HRQL instrument, and EQ5D visual analog scale at baseline, 4 months, 12 months, and annually thereafter. McMaster Overall Treatment Evaluation was assessed at 4 and 12 months to assess global change scores. Change scores (+SD) were calculated to determine between-group differences, and multivariable repeated-measures models were created to identify other factors associated with change scores. Paired KCCQ data were available for 91.7% of 3445 TOPCAT patients. By 4 months, the mean change in KCCQ was 7.7±16 and mean change in EQ5D visual analog scale was 4.7±16. Adjusted mean changes in KCCQ for the spironolactone group were significantly better than those for the placebo group at 4-month (1.54 better; P=0.002), 12-month (1.35 better; P=0.02), and 36-month (1.86 better; P=0.02) visits. No between-group differences in EQ5D visual analog scale change scores or McMaster Overall Treatment Evaluation were noted. Older age, obesity, current smoking, New York Heart Association class III/IV, and comorbid illnesses were associated with declines in KCCQ scores. Use of spironolactone was an independent predictor of improved KCCQ scores. CONCLUSIONS: In symptomatic HF with preserved ejection fraction patients, use of spironolactone was associated with an improvement in HF-specific HRQL. Several modifiable risk factors were associated with HRQL deterioration. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

Contemporary results of carotid endarterectomy in "normal-risk" patients from the Society for Vascular Surgery Vascular Registry.

OBJECTIVE: Acceptable complication rates after carotid endarterectomy (CEA) are drawn from decades-old data. The recent Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated improved stroke and mortality outcomes after CEA compared with carotid artery stenting, with 30-day periprocedural CEA stroke rates of 3.2% and 1.4% for symptomatic (SX) and asymptomatic (ASX) patients, respectively. It is unclear whether these target rates can be attained in "normal-risk" (NR) patients experienced outside of the trial. This study was done to determine the contemporary results of CEA from a broader selection of NR patients. METHODS: The Society for Vascular Surgery (SVS) Vascular Registry was examined to determine in-hospital and 30-day event rates for NR, SX, and ASX patients undergoing CEA. NR was defined as patients without anatomic or physiologic risk factors as defined by SVS Carotid Practice Guidelines. Raw data and risk-adjusted rates of death, stroke, and myocardial infarction (MI) were compared between the ASX and SX cohorts. RESULTS: There were 3977 patients (1456 SX, 2521 ASX) available for comparison. The SX group consisted of more men (61.7% vs 57.0%; P = .0045) but reflected a lower proportion of white patients (91.3% vs 94.4%; P = .0002), with lower prevalence of coronary artery disease (P < .0001), prior MI (P < .0001), peripheral vascular disease (P = .0017), and hypertension (P = .029), although New York Heart Association grade >3 congestive heart failure was equally present in both groups (P = .30). Baseline stenosis >80% on duplex imaging was less prevalent among SX patients (54.2% vs 67.8%; P < .0001). Perioperative stroke rates were higher for SX patients in the hospital (2.8% vs 0.8%; P < .0001) and at 30 days (3.4% vs 1.0%; P < .0001), which contributed to the higher composite death, stroke, and MI rates in the hospital (3.6% vs 1.8; P = .0003) and at 30 days (4.5% vs 2.2%; P < .0001) observed in SX patients. After risk adjustment, the rate of stroke/death was greater among SX patients in the hospital (odds ratio, 2.05; 95% confidence interval, 1.18-3.58) although not at 30 days (odds ratio, 1.36; 95% confidence interval, 0.85-2.17). No in-hospital or 30-day differences were observed for death or MI by symptom status. CONCLUSIONS: The SVS Vascular Registry results for CEA in NR patients are similar by symptom status to those reported for CREST and may serve as a benchmark for comparing results of alternative therapies for treatment of carotid stenosis in NR patients outside of monitored clinical trials. The contemporary perioperative risk of stroke after CEA in NR patients continues to be higher for SX than for ASX patients.

Baseline distribution of participants with depression and impaired quality of life in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial.

BACKGROUND: Previous studies have demonstrated the psychosocial effect of heart failure in patients with reduced ejection fraction. However, the effects on patients with preserved ejection fraction have not yet been elucidated. This study aimed to determine the baseline characteristics of participants with heart failure with preserved ejection fraction as it relates to impaired quality of life (QOL) and depression, identify predictors of poor QOL and depression, and determine the correlation between QOL and depression. METHODS AND RESULTS: Among patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT), 3400 patients completed the Kansas City Cardiomyopathy Questionnaire, 3395 patients completed European QOL 5D Visual Analog Scale, and 1431 patients in United States and Canada completed the Patient Health Questionnaire-9. The mean summary score on the Kansas City Cardiomyopathy Questionnaire was 54.8, and on European QOL 5D Visual Analog Scale, it was 60.3; 27% of patients had moderate to severe depression. Factors associated with better Kansas City Cardiomyopathy Questionnaire and European QOL 5D Visual Analog Scale via multiple logistic regression analysis were American region, older age, no history of angina pectoris or asthma, no use of hypoglycemic agent, more activity level, and lower New York Heart Association class. Factors associated with depression via multiple logistic regression analysis included younger age, female sex, comorbid angina, chronic obstructive pulmonary disease, use of a hypoglycemic agent, lower activity level, higher New York Heart Association class, and selective serotonin reuptake inhibitor use. There were significant correlations between each of the QOL scores and depression. CONCLUSIONS: Patients with heart failure with preserved ejection fraction, who were younger had higher New York Heart Association class or comorbid angina pectoris, had lower activity levels, lived in Eastern Europe or were taking hypoglycemic agents, were more likely to have impaired QOL and depression. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.

The influence of contralateral occlusion on results of carotid interventions from the Society for Vascular Surgery Vascular Registry.

OBJECTIVE: Data on the influence of contralateral carotid occlusion (CCO) on carotid endarterectomy (CEA) are conflicting and are absent for carotid artery stenting (CAS). This study evaluated the influence of CCO on CEA and CAS. METHODS: We evaluated patients with and without CCO in the Society for Vascular Surgery Vascular Registry. Primary outcome was a composite of periprocedural death, stroke, or myocardial infarction (MI) (major adverse cardiovascular events [MACE]) and its individual components. Further analysis was done to identify the influence, if any, of symptom status on outcomes. RESULTS: There were 1128 CAS and 666 CEA patients with CCO. CAS patients were more often symptomatic with a greater incidence of coronary artery disease, congestive heart failure, diabetes, chronic obstructive pulmonary disease, and New York Heart Association class >III. Absolute risk of periprocedural MACE (2.7% for CAS vs. 4.2% for CEA), death (1.1% for CAS vs. 0.7% for CEA), stroke (2.1% for CAS vs. 3.1% for CEA), and MI (0.3% for CAS vs. 0.6% for CEA) was statistically equivalent for both. This equivalence was maintained when patients with CCO were segregated according to symptom status and after adjusting for periprocedural risk. There were 16,646 patients without contralateral occlusion (5698 CAS; 10,948 CEA). Patients without contralateral occlusion with CEA have better outcomes in periprocedural MACE (1.8% for patients without contralateral occlusion vs 4.2% for patients with CCO), and stroke (1.1% for patients without contralateral occlusion vs. 3.1% for patients with CCO) (P < .0001 for both). In CAS patients, CCO did not significantly affect periprocedural MACE (3.2% for patients without contralateral occlusion vs. 2.7% for patients with CCO), death (0.8% for patients without contralateral occlusion vs. 1.0% for patients with CCO), stroke (2.3% for patients without contralateral occlusion vs. 2.1% for patients with CCO), or MI (0.6% for patients without contralateral occlusion vs. 0.3% for patients with CCO). In CEA patients, CCO increased MACE, primarily by increasing stroke rates in asymptomatic (0.7% vs. 2.0%; P = .0095) and symptomatic (1.7% vs. 4.9%; P = .0012) patients. CONCLUSIONS: Although CEA is preferred in patients without contralateral occlusion, regardless of symptom status, based on lower rates of periprocedural MACE, death, and stroke, the benefit of CEA is lost in patients with CCO because of increased stroke rates in CCO patients after CEA but not after CAS regardless of symptom status. The results of CAS and CEA in patients with CCO are equivalent and within acceptable American Heart Association guidelines.

Preoperative symptom type influences the 30-day perioperative outcomes of carotid endarterectomy and carotid stenting in the Society for Vascular Surgery Vascular Registry.

OBJECTIVE: The objective of this study was to determine the effect of presenting symptom types on 30-day periprocedural outcomes of carotid endarterectomy (CEA) and carotid artery stenting (CAS) in contemporary vascular practice. METHODS: Retrospective review was undertaken of the Society for Vascular Surgery Vascular Registry database subjects who underwent CEA or CAS from 2004 to 2011. Patients were grouped by discrete 12-month preprocedural ipsilateral symptom type: stroke, transient ischemic attack (TIA), transient monocular blindness (TMB), or asymptomatic (ASX). Risk-adjusted odds ratios (ORs) were used to compare the likelihood of the 30-day outcomes of death, stroke, and myocardial infarction (MI) and the composite outcomes of death + stroke and death + stroke + MI. RESULTS: Symptom type significantly influences risk-adjusted 30-day outcomes for carotid intervention. Presentation with stroke predicted the poorest outcomes (death + stroke + MI composite: OR, 1.3; 95% confidence interval [CI], 0.83-2.03 vs TIA; OR, 2.56; 95% CI, 1.18-5.57 vs TMB; OR, 2.12; 95% CI, 1.46-3.08 vs ASX), followed by TIA (death + stroke + MI composite: OR, 1.97; 95% CI, 0.91-4.25 vs TMB; OR, 1.63; 95% CI, 1.14-2.33 vs ASX). For both CAS and CEA patients, presentation with stroke or TIA predicted a higher risk of periprocedural stroke than in ASX patients. Presentation with stroke predicted higher 30-day risk of death with CAS but not with CEA. MI rates were not affected by presenting symptom type. The 30-day outcomes for the TMB and ASX patient groups were equivalent in both treatment arms. CONCLUSIONS: Presenting symptom type significantly affects the 30-day outcomes of both CAS and CEA in contemporary vascular surgical practice. Presentation with stroke and TIA predicts higher rates of periprocedural complications, whereas TMB presentation predicts a periprocedural risk profile similar to that of ASX disease.

Spironolactone for heart failure with preserved ejection fraction.

BACKGROUND: Mineralocorticoid-receptor antagonists improve the prognosis for patients with heart failure and a reduced left ventricular ejection fraction. We evaluated the effects of spironolactone in patients with heart failure and a preserved left ventricular ejection fraction. METHODS: In this randomized, double-blind trial, we assigned 3445 patients with symptomatic heart failure and a left ventricular ejection fraction of 45% or more to receive either spironolactone (15 to 45 mg daily) or placebo. The primary outcome was a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. RESULTS: With a mean follow-up of 3.3 years, the primary outcome occurred in 320 of 1722 patients in the spironolactone group (18.6%) and 351 of 1723 patients in the placebo group (20.4%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.77 to 1.04; P=0.14). Of the components of the primary outcome, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group than in the placebo group (206 patients [12.0%] vs. 245 patients [14.2%]; hazard ratio, 0.83; 95% CI, 0.69 to 0.99, P=0.04). Neither total deaths nor hospitalizations for any reason were significantly reduced by spironolactone. Treatment with spironolactone was associated with increased serum creatinine levels and a doubling of the rate of hyperkalemia (18.7%, vs. 9.1% in the placebo group) but reduced hypokalemia. With frequent monitoring, there were no significant differences in the incidence of serious adverse events, a serum creatinine level of 3.0 mg per deciliter (265 µmol per liter) or higher, or dialysis. CONCLUSIONS: In patients with heart failure and a preserved ejection fraction, treatment with spironolactone did not significantly reduce the incidence of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure. (Funded by the National Heart, Lung, and Blood Institute; TOPCAT ClinicalTrials.gov number, NCT00094302.).

Physical activity and body mass index: the contribution of age and workplace characteristics.

BACKGROUND: The workplace is an important domain for adults, and many effective interventions targeting physical activity and weight reduction have been implemented in the workplace. However, the U.S. workforce is aging, and few studies have examined the relationship of BMI, physical activity, and age as they relate to workplace characteristics. PURPOSE: This paper reports on the distribution of physical activity and BMI by age in a population of hospital-based healthcare workers and investigates the relationships among workplace characteristics, physical activity, and BMI. METHODS: Data from a survey of patient care workers in two large academic hospitals in the Boston area were collected in late 2009 and analyzed in early 2013. RESULTS: In multivariate models, workers reporting greater decision latitude (OR=1.02, 95% CI=1.01, 1.03) and job flexibility (OR=1.05, 95% CI=1.01, 1.10) reported greater physical activity. Overweight and obesity increased with age (p<0.01), even after adjusting for workplace characteristics. Sleep deficiency (OR=1.56, 95% CI=1.15, 2.12) and workplace harassment (OR=1.62, 95% CI=1.20, 2.18) were also associated with obesity. CONCLUSIONS: These findings underscore the persistent impact of the work environment for workers of all ages. Based on these results, programs or policies aimed at improving the work environment, especially decision latitude, job flexibility, and workplace harassment should be included in the design of worksite-based health promotion interventions targeting physical activity or obesity.

Gender-specific 30-day outcomes after carotid endarterectomy and carotid artery stenting in the Society for Vascular Surgery Vascular Registry.

OBJECTIVE: Although the optimal treatment of carotid stenosis remains unclear, available data suggest that women have higher risk of adverse events after carotid revascularization. We used data from the Society for Vascular Surgery Vascular Registry to determine the effect of gender on outcomes after carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: There were 9865 patients (40.6% women) who underwent CEA (n = 6492) and CAS (n = 3373). The primary end point was a composite of death, stroke, and myocardial infarction at 30 days. RESULTS: There was no difference in age and ethnicity between genders, but men were more likely to be symptomatic (41.6% vs 38.6%; P < .003). There was a higher prevalence of hypertension and chronic obstructive pulmonary disease in women, whereas men had a higher prevalence of coronary artery disease, history of myocardial infarction, and smoking history. For disease etiology in CAS, restenosis was more common in women (28.7% vs 19.7%; P < .0001), and radiation was higher in men (6.2% vs 2.6%; P < .0001). Comparing by gender, there were no statistically significant differences in the primary end point for CEA (women, 4.07%; men, 4.06%) or CAS (women, 6.69%; men, 6.80%). There remains no difference after stratification by symptomatology and multivariate risk adjustment. CONCLUSIONS: In this large, real-world analysis, women and men demonstrated similar results after CEA or CAS. These data suggest that, contrary to previous reports, women do not have a higher risk of adverse events after carotid revascularization.

The impact of Centers for Medicare and Medicaid Services high-risk criteria on outcome after carotid endarterectomy and carotid artery stenting in the SVS Vascular Registry.

OBJECTIVE: The Centers for Medicare and Medicaid Services (CMS) require high-risk (HR) criteria for carotid artery stenting (CAS) reimbursement. The impact of these criteria on outcomes after carotid endarterectomy (CEA) and CAS remains uncertain. Additionally, if these HR criteria are associated with more adverse events after CAS, then existing comparative effectiveness analysis of CEA vs CAS may be biased. We sought to elucidate this using data from the SVS Vascular Registry. METHODS: We analyzed 10,107 patients undergoing CEA (6370) and CAS (3737), stratified by CMS HR criteria. The primary endpoint was composite death, stroke, and myocardial infarction (MI) (major adverse cardiovascular event [MACE]) at 30 days. We compared baseline characteristics and outcomes using univariate and multivariable analyses. RESULTS: CAS patients were more likely to have preoperative stroke (26% vs 21%) or transient ischemic attack (23% vs 19%) than CEA. Although age ≥ 80 years was similar, CAS patients were more likely to have all other HR criteria. For CEA, HR patients had higher MACEs than normal risk in both symptomatic (7.3% vs 4.6%; P < .01) and asymptomatic patients (5% vs 2.2%; P < .0001). For CAS, HR status was not associated with a significant increase in MACE for symptomatic (9.1% vs 6.2%; P = .24) or asymptomatic patients (5.4% vs 4.2%; P = .61). All CAS patients had MACE rates similar to HR CEA. After multivariable risk adjustment, CAS had higher rates than CEA for MACE (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0-1.5), death (OR, 1.5; 95% CI, 1.0-2.2), and stroke (OR, 1.3; 95% CI,1.0-1.7), whereas there was no difference in MI (OR, 0.8; 95% CI, 0.6-1.3). Among CEA patients, age ≥ 80 (OR, 1.4; 95% CI, 1.02-1.8), congestive heart failure (OR, 1.7; 95% CI, 1.03-2.8), EF <30% (OR, 3.5; 95% CI, 1.6-7.7), angina (OR, 3.9; 95% CI, 1.6-9.9), contralateral occlusion (OR, 3.2; 95% CI, 2.1-4.7), and high anatomic lesion (OR, 2.7; 95% CI, 1.33-5.6) predicted MACE. Among CAS patients, recent MI (OR, 3.2; 95% CI, 1.5-7.0) was predictive, and radiation (OR, 0.6; 95% CI, 0.4-0.8) and restenosis (OR, 0.5; 95% CI, 0.3-0.96) were protective for MACE. CONCLUSIONS: Although CMS HR criteria can successfully discriminate a group of patients at HR for adverse events after CEA, certain CMS HR criteria are more important than others. However, CEA appears safer for the majority of patients with carotid disease. Among patients undergoing CAS, non-HR status may be limited to restenosis and radiation.

Society for Vascular Surgery (SVS) Vascular Registry evaluation of comparative effectiveness of carotid revascularization procedures stratified by Medicare age.

OBJECTIVE: Recent randomized controlled trials have shown that age significantly affects the outcome of carotid revascularization procedures. This study used data from the Society for Vascular Surgery Vascular Registry (VR) to report the influence of age on the comparative effectiveness of carotid endarterectomy (CEA) and carotid artery stenting (CAS). METHODS: VR collects provider-reported data on patients using a Web-based database. Patients were stratified by age and symptoms. The primary end point was the composite outcome of death, stroke, or myocardial infarction (MI) at 30 days. RESULTS: As of December 7, 2010, there were 1347 CEA and 861 CAS patients aged < 65 years and 4169 CEA and 2536 CAS patients aged ≥ 65 years. CAS patients in both age groups were more likely to have a disease etiology of radiation or restenosis, be symptomatic, and have more cardiac comorbidities. In patients aged <65 years, the primary end point (5.23% CAS vs 3.56% CEA; P = .065) did not reach statistical significance. Subgroup analyses showed that CAS had a higher combined death/stroke/MI rate (4.44% vs 2.10%; P < .031) in asymptomatic patients but there was no difference in the symptomatic (6.00% vs 5.47%; P = .79) group. In patients aged ≥ 65 years, CEA had lower rates of death (0.91% vs 1.97%; P < .01), stroke (2.52% vs 4.89%; P < .01), and composite death/stroke/MI (4.27% vs 7.14%; P < .01). CEA in patients aged ≥ 65 years was associated with lower rates of the primary end point in symptomatic (5.27% vs 9.52%; P < .01) and asymptomatic (3.31% vs 5.27%; P < .01) subgroups. After risk adjustment, CAS patients aged ≥ 65 years were more likely to reach the primary end point. CONCLUSIONS: Compared with CEA, CAS resulted in inferior 30-day outcomes in symptomatic and asymptomatic patients aged ≥ 65 years. These findings do not support the widespread use of CAS in patients aged ≥ 65 years.

Society for Vascular Surgery Vascular Registry evaluation of stent cell design on carotid artery stenting outcomes.

OBJECTIVE: The Society for Vascular Surgery (SVS) Vascular Registry (VR) collects data on outcomes of carotid endarterectomy and carotid artery stenting (CAS). The purpose of this study was to evaluate the impact of open vs closed cell stent design on the in-hospital and 30-day outcome of CAS. METHODS: The VR collects provider-reported data on patients using a Web-based database. Data were analyzed both in-hospital and at 30 days postprocedure. The primary outcome is combined death/stroke/myocardial infarction (MI). RESULTS: As of October 14, 2009, there were 4337 CAS with discharge data and 2397 with 30-day data. Open cell stents (OPEN) were used in 3451 patients (79.6%), and closed cell stents (CLOSED) were used in 866 patients (20.4%). Baseline demographics showed no differences in age, gender, race, and ethnicity. However, the OPEN group had more patients with atherosclerosis (74.5% vs 67.4%; P = .0003) as the etiology of carotid artery disease. The OPEN group also had a higher prevalence of preprocedural stroke (25.8% vs 21.4%; P = .0079), chronic obstructive pulmonary disease (COPD; 21.0% vs 17.6%; P = .0277), cardiac arrhythmia (14.7% vs 11.4%; P = .0108), valvular heart disease (7.4% vs 3.7%; P < .0001), peripheral vascular disease (PVD; 40.0% vs 35.3%; P = .0109), and smoking history (59.0% vs 54.1%; P = .0085). There are no statistically significant differences in the in-hospital or 30-day outcomes between the OPEN and CLOSED patients. Further subgroup analyses demonstrated symptomatic patients had a higher event rate than the asymptomatic cohort in both the OPEN and CLOSED groups. Among symptomatic patients, the OPEN patients had a lower (0.43% vs 1.41%; P = .0349) rate of in-hospital mortality with no difference in stroke or transient ischemic attack (TIA). There were no differences in 30-day event rates. In asymptomatic patients, there were also no statistically significant differences between the OPEN and CLOSED groups. After risk adjustment, there remained no statistically significant differences between groups of the primary endpoint (death/stroke/MI) during in-hospital or 30 days. CONCLUSION: In-hospital and 30-day outcomes after CAS were not significantly influenced by stent cell design. Symptomatic patients had higher adverse event rates compared to the asymptomatic cohort. As there is no current evidence of differential outcome between the use of open and closed cell stents, physicians should continue to use approved stent platforms based on criteria other than stent cell design.