Diabetes, quality of care, and in-hospital outcomes in patients hospitalized with heart failure

Congestive Heart Failure

Diabetes, quality of care, and in-hospital outcomes in patients hospitalized with heart failure John R. Kapoor, MD, PhD, a Gregg C. Fonarow, MD, b Xin Zhao, PhD, c Roger Kapoor, MD, MBA, d Adrian F. Hernandez, MD, MHS, c and Paul A. Heidenreich, MD, MS e Chicago, IL; Los Angeles, and Palo Alto, CA; Durham, NC; and Boston, MA

Background Diabetes mellitus is frequently comorbid with heart failure (HF). It is unclear if comorbid diabetes is associated with quality of care and in-hospital mortality. Methods We analyzed 133,971 HF admissions from 431 hospitals between January 2005 and January 2010 comparing patients with and without diabetes. Results

There were 54,352 (41%) patients hospitalized with HF with a history or newly diagnosed diabetes. After adjustment, patients with diabetes were as likely as patients without diabetes to appropriately receive the composite of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and β-blockers (odds ratio [OR] 0.99, 95% CI 0.941.04), angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (OR 0.98, 95% CI 0.92-1.05), evidence-based β-blockers (OR 1.04, 95% CI 0.98-1.1), and hydralazine/nitrates (OR 1.09, 95% CI 0.99-1.2). However, patients with diabetes were less likely to receive smoking cessation counseling (OR 0.89, 95% CI 0.81-0.98) and blood pressure control (OR 0.81, 95% CI 0.78-0.84) and to attain the all-or-none composite measure (OR 0.96, 95% CI 0.93-0.99). Patients with diabetes were more likely to receive an aldosterone antagonist for reduced left ventricular ejection fraction (OR 1.05, 95% CI 1.00-1.11), lipid-lowering agent (OR 1.33, 95% CI 1.26-1.41), and influenza vaccination (OR 1.05, 95% CI 1.01-1.09). Diabetes was independently associated with longer hospital stay but not within-hospital mortality.

Conclusions With few exceptions, the application of evidence-based care and in-hospital outcomes were similar whether or not diabetes was present in this large contemporary cohort of patients hospitalized with HF. (Am Heart J 2011;162:480-486.e3.)

The incidence and prevalence of heart failure (HF) continue to rise, and HF is a major cause of morbidity and mortality. 1 Commonly comorbid with HF, a history of diabetes mellitus portends a worse prognosis in patients with chronic HF and reduced left ventricular ejection fraction (LVEF). 2,3 Studies show that evidence-based therapies including angiotensin-converting enzyme inhibitors (ACEIs), β-blockers, and aldosterone antagonists reduce morbidity and mortality in patients with HF and reduced LVEF, and this benefit extends to HF patients with diabetes. 4-6 Nonetheless, morbidity and mortality remain high in HF patients with diabetes. To what degree a patient's history of comorbid diabetes might explain quality of care and outcome in hospitalized From the aUniversity of Chicago Pritzker School of Medicine, Chicago, IL, bAhmanson– University of California, Los Angeles, Cardiomyopathy Center, Los Angeles, CA, cDuke Clinical Research Institute, Durham, NC, dHarvard Medical School/Massachusetts General Hospital, Boston, MA, and eVeterans Affairs Palo Alto Health Care System, Palo Alto, CA. James L Januzzi, MD, served as guest editor for this article. Submitted March 11, 2011; accepted June 6, 2011. Reprint requests: John R. Kapoor, MD, PhD, University of Chicago, Pritzker School of Medicine, 5841 S Maryland Ave, Chicago, IL 60031. 0002-8703/$ - see front matter © 2011, Mosby, Inc. All rights reserved. doi:10.1016/j.ahj.2011.06.008

patients with HF is largely unknown. It is unclear if differences exist in the use of guideline-based therapies in HF patients with diabetes when compared with patients with HF without diabetes. Indeed, a few studies suggest that despite the known benefits of using β-blockers in patients with HF and diabetes, 7,8 they are underused because of concerns that they may have untoward metabolic ramifications. 9,10 Even less is known about the degree to which possible differences in quality of care and outcomes occur in HF patients with preserved LVEF and diabetes. Determining possible differences in quality of care and outcomes in patients based on the presence of diabetes is warranted to both develop interventions aimed at improving adherence to HF quality of care measures and outcomes. Get With The Guidelines-HF (GWTG-HF) prospectively tracks several performance measures and other quality of care indicators for hospitalized patients with HF. 11,12 In this study, we sought to investigate if differences exist in HF quality of care measures, hospital length of stay (LOS), and in-hospital mortality in HF patients with comorbid diabetes. The goal was to clarify the influence of diabetes on health care quality and in-hospital outcomes in a contemporary cohort of patients hospitalized with HF.

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Methods Data collection The GWTG-HF program is a national, prospective, observational, and ongoing voluntary data collection and continuous quality improvement initiative. 13,14 Hospitalized adults are enrolled in the registry with an episode of new or worsening HF as the primary reason for admission or with significant HF symptoms that developed during hospitalization in which HF was the primary discharge diagnosis. Hospitals from all census regions of the United States, including teaching and nonteaching, rural and urban, and large and small hospitals, are represented in the database. An online interactive case report form (Outcome Sciences, Inc, Cambridge, MA) is used by participating institutions to submit clinical information about consecutive eligible patients to the GWTG-HF database in compliance with Joint Commission and Centers for Medicare and Medicaid standards. Outcome Sciences, Inc, is the data collection coordination center for the American Heart Association GWTG programs. Standardized definitions are used to abstract clinic data. Demographic and clinical characteristics, medical history, previous treatments, contraindications to therapies, and outcomes are among the variables collected. Reported data are checked to ensure that it is complete, and completeness and accuracy of data quality are monitored. The GWTG protocol is reviewed and approved by institutional review boards. A waiver of informed consent is granted for sites under the common rule because data were used primarily at the local site for quality improvement. The data analysis center is the Duke Clinical Research Institute. Data are monitored for completeness and accuracy, and the aggregate deidentified data are analyzed for research purposes.

Study population The GWTG-HF population for this study consisted of 133,971 HF admissions from 431 fully participating sites between January 2005 and January 2010. The cohort was divided into those with reduced LVEF (LVEF b40% or, if LVEF was missing, qualitative assessment of moderate/severe dysfunction) and those with preserved LVEF (LVEF ≥40% or, if LVEF was missing, qualitative assessment of normal or mild dysfunction). There were 61,318 patients with HF and reduced LVEF and 63,888 patients with preserved LVEF and 8,765 patients (6.5%) with left ventricular function not measured. Data were analyzed by a medical history or new diagnosis of diabetes (yes/no).

Quality and outcome measures The following core measures used by the Centers for Medicare and Medicaid and The Joint Commission were the main prespecified quality of care outcomes measured 15,16: (1) complete discharge instructions; (2) documented evaluation of left ventricular function before arrival, during hospitalization, or planned after discharge; (3) ACEI or angiotensin receptor blocker (ARB) for HF patients with reduced LVEF without contraindications or intolerance; and (4) adult smoking cessation advice/counseling for patients with a history of smoking cigarettes. An additional measure used by GWTG-HF β-blocker use at discharge for patients with reduced LVEF without contraindications or intolerance was also included. Two composite measures established by the GWTG-HF program were

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also assessed. One composite quality measure was an opportunity quality of care index that was based on the number of therapeutic interventions in relation to the circumstances when those interventions were indicated for the 5 measures (number of successful interventions with quality measure/ number of patients eligible for quality measure). The other composite measure was an all-or-none measure for care with all 5 quality measures (whether eligible patients received 100% of guideline-based therapy, up to a maximum of all 5 measures). Additional quality measures of interest included (1) anticoagulant at discharge for patients with atrial fibrillation, (2) aldosterone antagonists prescribed at discharge for reduced LVEF, (3) hydralazine/nitrates in African American patients with reduced LVEF, (4) evidence-based–specific β-blocker (carvedilol, metoprolol succinate, bisoprolol fumarate) prescribed at discharge for patients with reduced LVEF, (5) implantable cardioverter defibrillator placed or prescribed at discharge for patients with LVEF ≤35%, (6) ACEI/ARB and β-blocker for reduced LVEF at discharge, and (7) prescription for a lipid-lowering agent for patients with coronary artery disease, cerebrovascular disease, peripheral vascular disease, and/or diabetes. The use of deep venous thrombosis (DVT) prophylaxis and administration of the influenza and pneumococcal vaccinations were also assessed starting in 2008. Hospital LOS and in-hospital deaths were also assessed.

Statistical analysis Baseline characteristics were compared between groups using the Pearson χ 2 test for categorical variables and the KruskalWallis test for continuous variables. Categorical variables were reported as percentages, and continuous variables were reported as mean ± SD for normally distributed variables and median (interquartile range) for nonnormally distributed variables. Multivariable logistic regression was performed using the generalized estimating equation (GEE) methods to adjust for clustering within hospitals to determine whether comorbid diabetes independently influenced each outcome and quality of care measure. Log transformation was used for the LOS analysis to achieve an approximately normal distribution. We dichotomized LOS to compare LOS N4 days versus LOS b4 days (median). The model was adjusted for patient characteristics and medical history (age, race, sex, admission systolic blood pressure, heart rate, history of anemia, stroke, diabetes, chronic obstructive pulmonary disease, hypertension, atrial fibrillation/flutter, peripheral vascular disease, renal failure, depression, smoking status, and etiology of HF) and hospital characteristics (region, number of beds, academic status). A P value of b.05 was considered significant for all tests. All analyses were performed using SAS software (version 9.2; SAS Institute, Inc, Cary, NC). The authors are solely responsible for the design and conduct of this study, including all analyses, drafting and editing, and its final contents.

Results Baseline characteristics The total study cohort consisted of 133,971 patients hospitalized with a diagnosis of HF from 431 hospitals, of which 61,318 patients (45.8%) had documented reduced

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Table I. Baseline characteristics in the overall population stratified by presence of diabetes Characteristic Age (y), mean ± SD Women (%) Race/ethnicity (%) White Black Hispanic Insurance (%) No insurance Medicare Medicaid Other History (%) Atrial fibrillation Atrial flutter COPD or asthma Hyperlipidemia Hypertension Peripheral vascular disease Coronary artery disease Prior MI CVA/TIA HF Anemia Dialysis (chronic) Renal insufficiency Depression Ejection fraction b40% (%)

Total (N = 133971)

Diabetes (n = 54352)

No diabetes (n = 79619)

P

72 ± 14 49

71 ± 13 50

73 ± 15 49

b.0001 b.0001 b.0001

68 20 7

65 22 9

70 19 5

4.5 54.1 11.1 30.2

3.8 53.8 12.7 29.7

5.0 54.3 10.1 30.6

30.7 2.1 28.3 39.1 71.9 11.1 47.2 16.1 13.3 51.8 16.9 4.2 19.9 9.2 48.9

26.8 1.9 30.6 49.3 80.3 14.7 55 18.7 15.3 55.1 20.4 5.6 25.9 10.6 46.6

33.4 2.1 26.7 32.1 66.1 8.6 41.8 14.3 11.9 49.5 14.5 3.3 15.9 8.3 50.6

b.0001

b.0001 .0137 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001

Values are presented as % or median (interquartile range).

LVEF, and 63,888 patients (47.7%) had preserved LVEF. There were 54,352 patients (40.6%) documented to have a medical history of diabetes or a new diagnosis of diabetes. Of the patients with diabetes, 46.6% were treated with insulin before hospitalization. The baseline characteristics of the overall population stratified by these 2 groups are presented in Table I. The average age of the overall population was 72 ± 14 years, with a slightly younger age distribution observed in the diabetes group. Except for atrial fibrillation, atrial flutter, valvular heart disease, and a prior smoking history (which were higher in the group without diabetes), patients with diabetes had more comorbidities (chronic obstructive pulmonary disease [COPD]/asthma, hyperlipidemia, hypertension, peripheral vascular disease, coronary artery disease), prior myocardial infarction (MI), cerebrovascular accident (CVA)/transient ischemic attack (TIA), HF, anemia, renal insufficiency, and depression. The characteristics of the cohort with reduced LVEF stratified by the presence or absence of diabetes are displayed in Appendix Table B (online), and the characteristics of the cohort with preserved LVEF are displayed in Appendix Table C (online). There were 23,811 (39%) patients with diabetes in the cohort with reduced LVEF and 27,287 (43%) with diabetes in the cohort with preserved LVEF. Baseline characteristics were similar across these subgroups analyzed in this study (see online Appendix Tables B and C). In both

cohorts, except for atrial fibrillation, atrial flutter, valvular heart disease, and a prior smoking history (which were higher in the group without diabetes), patients with diabetes had more comorbid conditions.

Diabetes and quality of care Adherence to quality measures by the presence or absence of diabetes is shown in Table II. There were a slightly higher proportion of the patients without diabetes who received ACEI/ARB prescriptions at discharge (90%) compared with patients with diabetes (89%). Similarly, HF patients with reduced LVEF without diabetes were more likely to receive discharge instructions and smoking cessation counseling. To the contrary, patients with diabetes were slightly more likely to receive evidencebased specific β-blockers for reduced LVEF, hydralazine and isosorbide dinitrate combination for reduced LVEF, lipid-lowering medication, and influenza and pneumococcal vaccinations. However, a higher proportion of patients without diabetes achieved blood pressure control defined as systolic b140 mm Hg and diastolic b90 mm Hg. In the group with preserved LVEF, there were no differences seen between groups in the proportion of patients who received discharge instructions, smoking cessation counseling, or anticoagulation for atrial fibrillation, though a higher proportion of patients with diabetes

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Table II. Quality measures and outcomes by presence of diabetes Characteristic

Total (N = 133971)

Diabetes (n = 54352)

No Diabetes (n = 79619)

P⁎

83.9 89.2 92.7 85.5 95.9 93.2 90.6 (21.1) 79.5 25.9 62.3 73.3 26.2

83.7 88.8 92.9 85.3 95.9 92.7 90.7 (21.1) 79.7 26.1 62.7 73.9 28.7

84 89.5 92.6 85.6 95.9 93.5 90.6 (21.1) 79.4 25.8 62.0 72.9 24.7

.4371 .0257 .2047 .2346 .9291 .0369 .389 .2345 .4145 .1836 .0186 b.0001

75.3 49.7 58.1 23.4 27.9 79.7 21.6 2.9

71.6 51.1 60.3 25.2 29.6 79.7 21.6 2.6

78.1 48.6 54.9 22.2 26.6

b.0001 .0047 b.0001 b.0001 b.0001

3.2

b.0001

ACEI/ARB and β-blocker for reduced LVEF at discharge ACEI/ARB for reduced LVEF at discharge β-Blocker for reduced LVEF at discharge Discharge instructions Documentation of LV function Smoking cessation Composite performance measure (%), mean (SD)† 100% Compliance Aldosterone antagonist for reduced LVEF at discharge Anticoagulation for atrial fibrillation Evidence-based specific β-blockers for reduced LVEF Hydralazine and isosorbide dinitrate combination for reduced LVEF at discharge Blood pressure control at discharge DVT prophylaxis (available after 2008) Lipid-lowering at discharge Influenza vaccination during flu season (available after 2008) Pneumococcal vaccination (available after 2008) Diabetes treatment (available after 2008) Diabetes teaching (available after 2008) Outcomes: death

All tests treat the column variable as nominal. ⁎ P values are based on Pearson χ2 tests for all categorical row variables. † P values are based on χ2 rank-based group means score statistics for all continuous/ordinal row variables. This is equivalent to Wilcoxon tests.

received lipid-lowering medication, DVT prophylaxis, influenza vaccination, and pneumococcal vaccination. However, again there was a higher proportion of patients without achieved blood pressure control defined as systolic b140 mm Hg and diastolic b90 mm Hg (online Appendix Table D).

Association of diabetes with adjusted quality of care Similarities and differences in the performance measures pertaining to quality of care according to the presence of diabetes were seen after GEE multivariate regression analyses accounting for common patient and hospital characteristics and clustering of patients within hospitals (Table III). Patients with diabetes and reduced LVEF were just as likely as patients without diabetes to receive the composite of ACEI/ARB and β-blockers, ACEI/ ARB, evidence-based specific β-blockers, and hydralazine/nitrate. To the contrary, when compared with patients without diabetes, patients with diabetes were less likely to receive smoking cessation counseling, less likely to achieve the all-or-none measure, and less likely to have achieved blood pressure control. However, patients with diabetes were more likely to receive an aldosterone antagonist for reduced LVEF, more likely to have been prescribed a lipid-lowering agent, and more likely to have received the influenza vaccine. Diabetes and hospital LOS The mean hospital LOS in the overall population and in the cohort with reduced LVEF was 5.7 days. The median

LOS was 4 (3-7) days in patients with diabetes and 4 (2-7) days in patients without diabetes (P b .0001). The overall proportion of patients with diabetes identified as having a LOS N4 days was 47% versus 43% in patients with no diabetes (P b .001). These findings were similarly found in the group with preserved LVEF, with 50% of patients with diabetes having a LOS N4 days compared with 46% of patients without diabetes having a LOS N4 days (P b .0001). These findings persisted after multivariable adjustment, wherein compared with patients without diabetes, patients with diabetes had longer hospital stays (Table IV). This was seen in the overall population, where LOS N4 days was higher in patients with diabetes and in the cohorts of patients with reduced LVEF and preserved systolic function.

Diabetes and in-hospital mortality There were 3,905 in-hospital deaths (2.9%) in the overall population during the study, with a slightly higher unadjusted death rate seen in the population without diabetes (3.2%) versus the diabetes group (2.6%) (Table II). In the group with reduced LVEF, there were 1,688 in-hospital deaths, and there were 1,612 in-hospital deaths in patients with preserved LVEF with slightly higher unadjusted in-hospital mortality in patients with no diabetes in the cohort with preserved LVEF. However, after multivariable adjustment for patient characteristics and laboratory values, there were no significant differences in rates of in-hospital mortality for those HF

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Table III. Multivariable models of performance and quality measures by the presence of diabetes Adjusted⁎

Unadjusted

OR

Lower (95% CI)

Upper (95% CI)

P

OR

Lower (95% CI)

Upper (95% CI)

P

0.990 0.950 1.050 0.971 0.971 0.906 1.002 1.020 1.018 1.057 1.237

0.947 0.900 0.986 0.942 0.941 0.844 0.975 0.971 0.971 1.008 1.113

1.035 1.003 1.119 1.000 1.001 0.972 1.030 1.071 1.068 1.109 1.374

.661 .062 .125 .050 .057 .006 .886 .439 .454 .022 b.001

0.991 0.982 0.987 0.991 0.916 0.893 0.962 1.054 0.958 1.039 1.091

0.940 0.921 0.906 0.957 0.867 0.811 0.933 1.004 0.912 0.982 0.992

1.044 1.047 1.076 1.027 0.968 0.984 0.992 1.108 1.006 1.100 1.201

.728 .577 .768 .622 .002 .022 .014 .035 .087 .182 .073

0.707

0.682

0.732

b.001

0.807

0.777

0.839

b.001

1.246 1.057 1.060

1.203 1.005 1.019

1.291 1.112 1.104

b.001 .032 .004

1.331 1.055 1.048

1.256 0.999 1.006

1.411 1.113 1.092

b.001 .055 .024

1.051

1.009

1.094

.017

1.039

0.997

1.082

.072

Outcome ACEI/ARB and β-blocker for reduced LVEF at discharge ACEI/ARB for reduced LVEF at discharge β-Blocker for reduced LVEF at discharge Discharge instructions Documentation of LV function † Patients with smoking history had smoking cessation Composite performance measure for 100% compliance Aldosterone antagonist for reduced LVEF at discharge Anticoagulation for atrial fibrillation Evidence-based specific β-blockers for reduced LVEF Hydralazine and isosorbide dinitrate combination for reduced LVEF at discharge Blood pressure control at discharge: systolic b140 mm Hg and diastolic b90 mm Hg Lipid-lowering medications at discharge DVT prophylaxis (available after 2008) Influenza vaccination during flu season (available after 2008) Pneumococcal vaccination (available after 2008)

⁎ Variables in the model—diabetes, age, gender, race, insurance, medical history of atrial fibrillation, atrial flutter, COPD or asthma, hyperlipidemia, hypertension, PVD, prior MI, CVA/TIA, HF, anemia, renal insufficiency, smoking, ischemic history, ejection fraction, hospital size, hospital type, and region. † Documentation of LV function—ejection fraction not included in this model.

Table IV. Multivariable models of clinical outcomes by the presence of diabetes Adjusted⁎

Unadjusted Outcome In-hospital mortality In-hospital mortality—EF b40% In-hospital mortality—EF ≥40% LOS N4 d LOS N4 d—EF b40% LOS N4 d—EF ≥40%

OR

Lower (95% CI)

Upper (95% CI)

P

OR

Lower (95% CI)

Upper (95% CI)

P

0.823 0.986 0.803 1.170 1.196 1.143

0.771 0.898 0.720 1.143 1.153 1.109

0.878 1.083 0.897 1.197 1.241 1.177

b.001 .769 b.001 b.001 b.001 b.001

0.942 1.018 0.953 1.184 1.211 1.175

0.876 0.926 0.843 1.155 1.163 1.135

1.014 1.119 1.076 1.214 1.261 1.217

.111 .713 .436 b.001 b.001 b.001

Documentation of LV function—ejection fraction not included in this model. ⁎ Variables in the model per Table III.

patients with compared with those without diabetes in the overall population or in either the cohort with reduced LVEF or preserved LVEF (Table IV).

Discussion This analysis from GWTG-HF demonstrates, with few exceptions, that the application of evidence-based care was similar whether or not a patient had diabetes in this large contemporary cohort of patients hospitalized with HF throughout the United States. Use of ACEI/ARB and βblockers in eligible patients at hospital discharge was high, and there were no differences based on comorbid diabetes. Some differences in care were seen in HF patients based on comorbid diabetes. Specifically, when compared with patients without diabetes, patients with

diabetes were less likely to receive smoking cessation counseling, less likely to achieve the composite performance measure for 100% compliance, and less likely to have achieved blood pressure control. However, patients with diabetes were more likely to receive an aldosterone antagonist for reduced LVEF, be prescribed a lipidlowering agent, and receive the influenza vaccination. In addition, there were a higher proportion of HF patients with diabetes with a LOS N4 days when compared with HF patients without diabetes. There were similar findings in separate analyses of HF patients with reduced LVEF and preserved LVEF. Finally, although differences were seen in the application of evidence-based, guidelinerecommended therapies and hospital LOS, no significant differences were seen in risk-adjusted in-hospital mortality rates in the overall population or in either the cohorts

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with reduced LVEF or preserved LVEF. These findings have important implications for the assessment and care of hospitalized patients with HF and diabetes. This GWTG-HF study demonstrates a very high prevalence of diabetes among hospitalized patients with HF with 40.6% having diabetes documented. In Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), 42% of the HF patients enrolled had diabetes documented. 17 In the Acute Decompensated Heart Failure National Registry (ADHERE), it was reported that 44% of hospitalized patients with HF have diabetes. 18 These findings are in contrast to randomized clinical trials in HF that have generally enrolled populations with a substantially lower prevalence of diabetes. It is also notable that in the present study, the prevalence of diabetes among HF patients with reduced and preserved LVEF was similar. Despite major advances in the HF treatments, prior studies suggest poor long-term outcomes in patients with diabetes and HF compared with HF patients without diabetes. Comorbid diabetes may influence application of evidence-based care in the treatment of HF patients. Diabetes may bias decision making by health care providers and prevent patients from receiving appropriate care. For example, a few studies suggest that βblockers may be underused in HF and diabetes because of concerns that they may have untoward metabolic ramifications. 9,10 However, there is a lack of studies assessing the influence of diabetes on quality of care and outcomes in patients with HF. Our study provides additional insights demonstrating that in the context of a performance improvement registry, hospitalized patients with HF and diabetes, with few exceptions, are treated with guideline-recommended HF therapies at a similar rate to those without diabetes. Furthermore, diabetes was not associated with an increase in riskadjusted in-hospital mortality. These results suggest that aggressive evidence-based therapies are warranted in HF patients with and without diabetes. Our data in some ways parallel to findings from OPTIMIZE-HF. OPTIMIZE-HF also found similar mortality between groups of HF patients with and without diabetes. Heart failure patients with diabetes also experienced modestly longer hospital LOS in OPTMIZEHF similar to the current study. Comparable with OPTIMIZE-HF, the current study also demonstrated similarities between groups in the application of wellestablished quality care measures in HF, including ACEI/ ARB, β-blockers, and evidence-based β-blockers. There was, however, modestly less smoking cessation counseling and measurement LV function in patients with diabetes who were also less likely to achieve optimal blood pressure control. Although diabetes is associated with increased longterm mortality in patients with chronic HF, 19-22 less is known regarding the association with in-hospital mortal-

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ity and how that may vary by LVEF group. 23,24 Lee et al 23 completed a retrospective study of 4,031 patients hospitalized with HF, demonstrating that diabetes had no significant multivariable predictor effect on 30-day or 1-year mortality. On the other hand, Gustafsson et al 24 reported diabetes as a potent and independent risk factor for mortality in hospitalized patients with HF. Our findings are similar to the results reported by Lee et al, in that no significant impact on adjusted in-hospital mortality was noted when comparing HF patients with and without diabetes. During hospitalization for HF failure, diabetes may have little adverse effect on short-term mortality, but with longer term postdischarge follow-up, an adverse effect on prognosis may become evident. The mortality findings in this study could also have been influenced by the high use of evidence-based therapies among patients with diabetes in this study.

Limitations There are limitations to this study. First, although diabetes status was collected and analyzed, there were no direct measures regarding the degree of glycemic control, duration of diabetes, and diabetes medications other than insulin. Second, the lack of follow-up after discharge does not allow assessment of long-term outcomes. Third, data were collected by medical chart review and depend on the accuracy and completeness of documentation and abstraction. Although contraindications and intolerance to medications were recorded as documented in the medical record, there may have been patients with contraindications or intolerances to treatments that were present but not documented. Given the observational nature of the study, unobserved variables may have confounded the results. Although the GEE multivariable analyses were adjusted for multiple baseline differences, selection bias influencing physician and patient decision making may influence these findings. Furthermore, although this is a registry-based study with an opportunity to study patients in real-world setting, data collection is dependent on voluntary participation of hospitals such that findings may not be generalizable to hospitals that differ in care patterns or patient characteristics. Finally, because of the large number of patients in this study, small differences might lead to statistical significance but lack clinical relevance.

Conclusions This study using data from the GWTG-HF quality program demonstrates a high prevalence of diabetes among patients hospitalized with HF. With few exceptions, the application of evidence-based care was similar whether or not a patient with HF had diabetes in this large contemporary cohort of patients. Risk-adjusted in-hospital mortality was similar in the presence of diabetes, yet riskadjusted hospital LOS was longer among HF patients with

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diabetes. These findings provide additional support for the use of the full complement of evidence-based therapies in patients with HF and diabetes.

Disclosures John Kapoor, Roger Kapoor, and Xin Zhao have no conflicts of interest. Adrian Hernandez was supported by Research Johnson & Johnson, Proventys, and Amylin; Paul Heidenreich received a grant from Medtronic. Gregg Fonarow has received funding from Research National Heart, Lung, and Blood Institute and a consultant of Novartis, Medtronic, and Scios. Program disclosure: GWTG-HF program is provided by the American Heart Association. The GWTG-HF program is currently supported in part by Medtronic, OrthoMcNeil, and the American Heart Association Pharmaceutical Roundtable and, in the past, through support from GlaxoSmithKline.

References 1. McCullough PA, Philbin EF, Spertus JA, et al. Confirmation of a heart failure epidemic: findings from the Resource Utilization Among Congestive Heart Failure (REACH) study. J Am Coll Cardiol 2002;39: 60-9. 2. Kannel WB, D'Agostino RB, Silbershatz H, et al. Profile for estimating risk of heart failure. Arch Intern Med 1999;159:1197-204. 3. Nichols GA, Hillier TA, Erbey JR, et al. Congestive heart failure in type 2 diabetes: prevalence, incidence, and risk factors. Diabetes Care 2001;24:1614-9. 4. MERIT-HF Investigators. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure. Lancet 1999;353:2001-7. 5. Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in COMET: randomised controlled trial. Lancet 2003;362:7-13. 6. Cohn JN, Tognoni G. A randomized trial of the angiotensin receptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345: 1667-75. 7. Hunt SA, Abraham WT, Chin MH, et al. Focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the ACCF/AHA Task Force on Practice Guidelines developed in collaboration with the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 2009;53:e1-90. 8. Lindenfeld J, Albert NM, Boehmer JP, et al. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail 2010;16:e1-194. 9. Giugliano D, Acampora R, Marfella R, et al. Metabolic and cardiovascular effects of carvedilol and atenolol in non–insulindependent diabetes mellitus and hypertension. Ann Intern Med 1997; 126:955-9.

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10. Jacob S, Rett K, Wicklmayr M, et al. Differential effect of chronic treatment with two beta-blocking agents on insulin sensitivity: the carvedilol-metoprolol study. J Hypertens 1996;14:489-94. 11. Fonarow GC, Abraham WT, Albert NM, et al. Influence of a performance-improvement initiative on quality of care for patients hospitalized with heart failure. Arch Intern Med 2007;167: 1493-502. 12. Fonarow GC, Abraham WT, Albert NM, et al. Association between performance measures and clinical outcomes for patients hospitalized with heart failure. JAMA 2007;297:61-70. 13. Hernandez AF, Fonarow GC, Liang L, et al. Sex and racial differences in the use of implantable cardioverter-defibrillators among patients hospitalized with heart failure. JAMA 2007;298:1525-32. 14. Fonarow GC, Abraham WT, Albert NM, et al. Organized program to initiate lifesaving treatment in hospitalized patients with heart failure. Am Heart J 2004;148:43-51. 15. Fonarow GC, Abraham WT, Albert NM, et al. Day of admission and clinical outcomes for patients hospitalized for heart failure: findings from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure. Circ Heart Fail 2008;1: 50-7. 16. Thomas KL, Hernandez AF, Dai D, et al. Association of race/ethnicity with clinical risk factors, quality of care, and acute outcomes in patients hospitalized with heart failure. Am Heart J 2011;161: 746-54. 17. Greenberg BH, Abraham WT, Albert NM, et al. Influence of diabetes on characteristics and outcomes in patients hospitalized with heart failure: a report from OPTIMIZE-HF. Am Heart J 2007; 154:277.e1-8. 18. Fonarow GC. The Acute Decompensated Heart Failure National Registry (ADHERE): opportunities to improve care of patients hospitalized with acute decompensated heart failure. Rev Cardiovasc Med 2003;4:S21-30. 19. Pocock SJ, Wang D, Pfeffer MA, et al. Predictors of mortality and morbidity in patients with chronic heart failure. Eur Heart J 2006;27: 65-75. 20. Shindler DM, Kostis JB, Yusuf S, et al. Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) trials and registry. Am J Cardiol 1996;77: 1017-20. 21. Domanski M, Krause-Steinrauf H, Deedwania P, et al. The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial. J Am Coll Cardiol 2003;42:914-22. 22. Dries DL, Sweitzer NK, Drazner MH, et al. Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction. J Am Coll Cardiol 2001;38:421-8. 23. Lee DS, Austin PC, Rouleau JL, et al. Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. JAMA 2003;290:2581-7. 24. Gustafsson I, Brendorp B, Seibaek M, et al. Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure. J Am Coll Cardiol 2004; 43:771-7.

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Appendix Appendix Table A. Baseline hospital characteristics in the overall population stratified by presence of diabetes Hospital characteristics

Total (N = 133971)

Diabetes (n = 54352)

No diabetes (n = 79619)

P†

375 (237-575) 83.5 69.3 11.7 67.5 61.9

381 (251-575) 84.5 70.4 11.5 68.9 62.7

357 (233-571) 82.9 68.5 11.8 66.6 61.3

b.0001 b.0001 b.0001 .0884 b.0001 b.0001 b.0001

13.9 31.3 22.5 32.4

12.1 32.2 23.3 32.4

15.1 30.6 21.9 32.4

No. of beds⁎ Primary PCI performed at hospital (%) Cardiac surgery performed at hospital (%) Heart transplants performed at hospital (%) Interventional hospital (%) Hospital type—academic (%) Region (%) West South Midwest Northeast Values are presented as % or median (interquartile range).

Appendix Table B. Baseline characteristics in patients with reduced LVEF Variable Demographics Age (y), mean ± SD (y) Women (%) Race (%) White Black Hispanic Insurance (%) No insurance Medicare Medicaid Other Medical history (%) Atrial fibrillation Atrial flutter COPD or asthma Hyperlipidemia Hypertension Peripheral vascular disease Coronary artery disease Prior MI CVA/TIA HF Anemia Dialysis (chronic) Renal insufficiency Depression Discharge status LOS (d), median (25th-75th) Death Hospital characteristics No. of beds⁎, median (25th-75th) Primary PCI performed at hospital (%) Cardiac surgery performed at hospital (%) Heart transplants performed at hospital (%) Interventional hospital (%) Hospital type—academic (%) Region (%) West South Midwest Northeast

Overall (N = 61318)

Diabetes (n = 23811)

No diabetes (n = 37507)

68.9 ± 14.8 36.8

68.7 ± 12.8 38.6

69.2 ± 15.9 35.6

63.1 25.2 7.0

62.0 24.5 9.2

63.8 25.6 5.6

6.4 50.4 11.6 31.6

4.9 51.9 12.3 30.8

7.3 49.3 11.2 32.1

27.5 2.2 25.8 40.5 68.7 10.9 50.6 20.8 12.5 56.3 13.6 3.1 19.5 7.9

25.9 2.00 28.1 50.9 77.3 14.8 59.7 24.40 14.8 59.4 16.8 4.2 25.1 9.3

28.6 2.3 24.3 33.9 63.2 8.3 44.8 18.6 11.1 54.3 11.5 2.4 16.0 7.0

b.0001 .0288 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001

4 (2-7) 2.8

4 (3-7) 2.8

4 (2-7) 2.8

b.0001 .9736

400 (270-581) 86.5 73.6 14.9 72.4 66.1

400 (288-581) 86.8 73.7 14.2 72.8 66.2

400 (270-581) 86.4 73.5 15.3 72.2 66.1

.0018 .1696 .5761 .0003 .1287 .8648 b.0001

13.6 31.3 22.4 32.7

12.0 31.9 23.4 32.7

14.5 30.9 21.8 32.8

P†

b.0001 b.0001 b.0001

b.0001

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Appendix Table C. Baseline characteristics in patients with preserved LVEF Variable Demographics Age (y), mean ± SD (y) Women (%) Race (%) White Black Hispanic Insurance (%) No insurance Medicare Medicaid Other Medical history (%) Atrial fibrillation Atrial flutter COPD or asthma Hyperlipidemia Hypertension Peripheral vascular disease Coronary artery disease Prior MI CVA/TIA HF Anemia Dialysis (chronic) Renal insufficiency Depression Discharge status LOS (d), median (25th-75th) Death Hospital characteristics No. of beds⁎, median (25th-75th) Primary PCI performed at hospital (%) Cardiac surgery performed at hospital (%) Heart transplants performed at hospital (%) Interventional hospital (%) Hospital type—academic Region (%) West South Midwest Northeast

Overall (N = 63888)

Diabetes (n = 27287)

No diabetes (n = 36601)

P†

74.83 ± 14.4 60.6

71.9 ± 12.7 59.4

77.1 ± 15.4 61.5

b.0001 b.0001 b.0001

72.5 16.6 6.0

67.4 19.9 8.1

76.3 14.1 4.5

3.0 57.0 10.7 29.4

3.0 54.9 12.9 29.2

3.0 58.6 9.0 29.4

33.8 2.1 30.8 39.4 75.8 11.5 44.6 12.5 14.1 49.5 20.2 4.8 20.5 10.4

27.9 1.9 32.8 49.5 83.3 14.6 51.6 14.8 15.9 53.3 23.7 6.2 26.6 11.7

38.3 2.2 29.3 31.8 70.1 9.2 39.4 10.8 12.8 46.7 17.5 3.8 15.9 9.4

b.0001 .0278 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001 b.0001

4 (3-7) 2.5

4 (3-7) 2.25

4 (3-7) 2.8

b.0001 b.0001

353 (230-571) 82.5 67.7 9.5 65.5 60.2

366 (238-571) 83.7 69.5 9.9 67.6 61.9

349 (218-553) 81.6 66.3 9.2 64.0 59.0

b.0001 b.0001 b.0001 .0025 b.0001 b.0001 b.0001

13.8 30.8 22.5 32.9

12.0 31.8 23.3 32.9

15.1 30.0 21.9 32.9

b.0001

Appendix Table D. Quality measures and outcomes in preserved LVEF

Discharge instructions Smoking cessation Composite performance measure for 100% compliance Anticoagulation for atrial fibrillation Blood pressure control at discharge: systolic b140 mm Hg and diastolic b90 mm Hg Lipid-lowering medications at discharge Influenza vaccination during flu season (available after 2008) DVT prophylaxis (available after 2008) Outcomes (%) LOS (d), median (25th-75th) Death

Overall (N = 63888)

Diabetes (n = 27287)

No diabetes (n = 36601)

P†

84.9 92.7 87.7 61.4 69.2

85.2 92.9 87.9 62.2 64.6

84.6 92.6 87.6 60.9 72.8

.0735 .5961 .2834 .0543 b.0001

56.9 24.9 49.9

59.8 26.2 52.1

52.3 23.9 48.2

b.0001 b.0001 .0012

4 (3-7) 2.5

4 (3-7) 2.25

4 (3-7) 2.8

b.0001 b.0001

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Appendix Table E. Quality measures and secondary outcomes in patients with reduced LVEF Variable Quality measures ACEI/ARB for reduced LVEF at discharge β-Blocker for reduced LVEF at discharge Discharge instructions Smoking cessation HF composite performance (%), mean (SD) 100% compliance Aldosterone antagonist for reduced LVEF at discharge Anticoagulation for atrial fibrillation Evidence-based specific β-blockers for reduced LVEF Hydralazine and isosorbide dinitrate combination for reduced LVEF at discharge ICD placed or prescribed at discharge for patients with LVEF ≤35% Blood pressure control at discharge: systolic b140 mm Hg and diastolic b90 mm Hg Lipid-lowering medications at discharge DVT prophylaxis (available after 2008) Influenza vaccination during flu season (available after 2008) Pneumococcal vaccination (available after 2008) Outcomes LOS (d), median (25th-75th) Death

Overall (N = 61318)

Diabetes (n = 23811)

No diabetes (n = 37507)

P†

89.2 92.7 88.1 94.4 92.9 (14.5) 77.8 25.9 64.8 73.3 26.3

88.8 92.9 87.7 93.7 92.8 (14.6) 77.4 26.1 64.2 73.9 28.7

89.5 92.6 88.4 94.8 93 (14.5) 78.0 25.8 65.2 72.9 24.7

.0257 .2047 .0290 .0125 .0625 .0785 .4145 .2328 .0186 b.0001

40.7 82.5

41.1 80.4

40.4 83.9

.1393 b.0001

61.2 50.1 22.5 26.8

62.8 50.7 24.5 28.9

59.3 49.7 21.2 25.4

b.0001 .4767 b.0001 b.0001

4 (2-7) 2.8

4 (3-7) 2.8

4 (2-7) 2.8

b.0001 .9736

All tests treat the column variable as nominal. ICD, Implantable cardioverter defibrillator. ⁎P values are based on χ2 rank-based group means score statistics for all continuous/ordinal row variables. This is equivalent to Wilcoxon tests. † P values are based on Pearson χ2 tests for all categorical row variables.