Venous Thromboembolism in Heart Failure: Preventable Deaths During and After Hospitalization

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1 CLINICAL RESEARCH STUDY Venous Thromboembolism in Heart : Preventable Deaths During and After Hospitalization Gregory Piazza, MD, a Samuel Z. Goldhaber, MD, a Darleen M. Lessard, MS, b Robert J. Goldberg, PhD, b Catherine Emery, RN, b Frederick A. Spencer, MD c a Cardiovascular Division, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, Mass; b Department of Medicine, University of Massachusetts Medical School, Worcester, Mass; c Department of Medicine, McMaster University, Hamilton, Ontario, Canada. ABSTRACT OBJECTIVE: Our aim was to compare the clinical characteristics, prophylaxis, treatment, and outcomes of patients with venous thromboembolism with and without heart failure. METHODS: We studied patients with heart failure in the population-based Worcester Venous Thromboembolism Study of 1822 consecutive patients with validated venous thromboembolism. RESULTS: Of the 1822 patients with venous thromboembolism, 319 (17.5%) had a history of clinical heart failure and 1503 (82.5%) did not. Patients with heart failure were older (mean age 75 vs 62 years, P.0001) and more likely to have been immobilized (65.2% vs 46.1%, P.0001). Thromboprophylaxis was omitted in approximately one third of patients with heart failure who had been hospitalized for non-venous thromboembolism-related illness or had undergone major surgery within the 3 months before diagnosis. Patients with heart failure had a higher frequency of in-hospital death (9.7% vs 3.3%, P.0001) and death within 30 days of venous thromboembolism diagnosis (15.6% vs 6.4%, P.0001). Heart failure (adjusted odds ratio [OR] 2.04; 95% confidence interval [CI], ) and immobility (adjusted OR 4.37; 95% CI, ) were associated with an increased risk of in-hospital death. Heart failure (adjusted OR 1.57; 95% CI, ) and immobility (adjusted OR 3.05; 95% CI, ) also were independent predictors of death within 30 days of venous thromboembolism diagnosis. CONCLUSION: High mortality was observed among patients with heart failure and venous thromboembolism both during and after hospitalization. Heart failure and immobility are potent risk factors for in-hospital death and death within 30 days in patients with venous thromboembolism Elsevier Inc. All rights reserved. The American Journal of Medicine (2011) 124, KEYWORDS: Deep vein thrombosis; Heart failure; Prophylaxis; Pulmonary embolism; Treatment; Venous thromboembolism Funding: This study was supported by a grant from the National Heart, Lung, and Blood Institute (R01-HL70283). Dr Spencer also has a Career Investigator Award from the Heart and Stroke Foundation of Canada. Dr Piazza is supported by a Research Career Development Award (K12 HL083786) from the National Heart, Lung, and Blood Institute. The sponsors had no role in the design and conduct of this study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. Conflict of Interest: None. Authorship: All authors had access to the data and played a role in writing this manuscript. Requests for reprints should be addressed to Gregory Piazza, MD, Cardiovascular Division, Brigham and Women s Hospital, 75 Francis St, Boston, MA address: gpiazza@partners.org. Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, is a common and preventable complication of heart failure. 1-4 In an analysis of the US Healthcare Cost and Utilization Project Nationwide Inpatient Sample database, approximately 2 million patients with heart failure were estimated to be at increased risk for venous thromboembolism, representing the largest population of atrisk medical patients. 5 The risk of pulmonary embolism among patients with heart failure increases as left ventricular systolic function declines. 6 Traditional venous thromboembolism risk factors, including cancer, chronic obstructive pulmonary disease, and immobilization, further amplify this risk. 7 Pulmonary embolism is an independent predictor of rehospitalization or death among patients with heart failure. 8,9 The current study /$ -see front matter 2011 Elsevier Inc. All rights reserved. doi: /j.amjmed

2 Piazza et al Venous Thromboembolism in Heart 253 compared the clinical characteristics, prophylaxis, treatment, and outcomes of 319 patients with heart failure with those of 1503 patients without heart failure in the Worcester Venous Thromboembolism Study of 1822 patients with validated venous thromboembolism. MATERIALS AND METHODS CLINICAL SIGNIFICANCE Patient Population Lists of patients were generated from health care system encounters in which any of 34 International Classification of Diseases, Ninth Revision diagnosis codes consistent with venous thromboembolism were used in 1999, 2001, and The study years were chosen according to funding cycles, the desire to track events over time, and the correlation with publication of updated American College of Chest Physicians guidelines for management of venous thromboembolism. Lists were obtained from each of the 12 medical centers serving residents of the Worcester, Massachusetts, metropolitan area. 10 Data queries included discharge diagnoses and outpatient, emergency department, radiology, and laboratory encounters. The medical records of all potentially eligible patients were reviewed by trained nurse abstractors using prespecified criteria to validate and characterize each case. 10 Each case of venous thromboembolism was classified as definite, probable, possible, or not acute or negative based on a modification of the classification used by Silverstein et al (Appendix). 11,12 In brief, definite diagnosis of deep vein thrombosis required evidence for presumed acute thrombosis by compression ultrasonography, computed tomography, magnetic resonance imaging, or venography. Definite diagnosis of pulmonary embolism required evidence for presumed new thrombosis on computed tomography or pulmonary angiography. Probable pulmonary embolism required the presence of a high-probability ventilation-perfusion lung scan. Cases of deep vein thrombosis or pulmonary embolism were classified as possible if these confirmatory tests were not performed, or were indeterminate, and the medical record indicated that the physician made a clinical diagnosis of deep vein thrombosis or pulmonary embolism, symptoms or signs of venous thromboembolism were documented, or the patient underwent therapy with anticoagulants or an inferior vena cava filter was inserted. If the classification of venous thromboembolism was not immediately clear using the specified criteria, the principal investigator (FAS) reviewed the medical record. Only definite, probable, and possible cases were included in the analysis. There were no exclusion criteria for entry into the registry. Patients with heart failure and venous thromboembolism demonstrate high mortality both during hospitalization and in the community setting. Heart failure and immobility are independent predictors of in-hospital death and death after hospital discharge among patients with venous thromboembolism. However, thromboprophylaxis is omitted with a high frequency in patients with heart failure. Data Collection Data regarding demographic characteristics, comorbidities, risk factors, diagnosis, management, prophylaxis, and outcomes were abstracted from the medical record. Patients with a history of clinical heart failure were classified as having heart failure, which may have been due to left ventricular systolic dysfunction, diastolic dysfunction, or a combination of both based on information contained in hospital and ambulatory care records. Surgery was defined as a major operation in which general or epidural anesthesia lasted at least 30 minutes. Immobility was defined as limited ambulation, restricted activity of bed-to-chair or bed-to-bathroom, or complete bed rest based on medical record documentation. Clinical characteristics defined as recent were those occurring or active within 3 months before venous thromboembolism diagnosis. Major bleeding was defined as any episode of bleeding that required transfusion or that resulted in a subsequent hospitalization, stroke, myocardial infarction, or death. Venous thromboembolism was considered provoked if deep vein thrombosis or pulmonary embolism occurred within 3 months of hospitalization, major surgery, pregnancy, trauma, or fracture. Information regarding the type of anticoagulation with respect to prophylaxis, initial management of venous thromboembolism, and discharge therapy was collected. Data regarding thromboprophylaxis use were obtained for patients who were hospitalized for any non-venous thromboembolism-related condition or who had major surgery within the 3 months before diagnosis of deep vein thrombosis or pulmonary embolism. This information was abstracted from medical records at the same time as data regarding the incident venous thromboembolism event. Medical records from other area hospitals were searched in case prior hospitalization was at a different institution than that of the index venous thromboembolism. First recurrence of venous thromboembolism or a major bleeding event was determined through review of medical records at the same hospital as the index event and screening of medical records from the other participating medical centers. Data regarding all-cause mortality were obtained through review of hospital records and death certificates at the Massachusetts Division of Vital Statistics. Median follow-up period was 891 days (interquartile range days; maximum follow-up period 1095 days). Statistical Methods The mean or median and frequency distributions were calculated for continuous variables. Differences in the distri-

3 254 The American Journal of Medicine, Vol 124, No 3, March 2011 bution of demographic characteristics, comorbidities, risk factors, diagnosis, management, prophylaxis, and outcomes were examined using the chi-square or Fisher exact test for categoric variables and t test for continuous variables. Cumulative incidence rates of venous thromboembolism recurrence, major bleeding, and all-cause mortality were estimated using the life-table method. All tests were 2-tailed, and a P value of less than.05 was considered statistically significant. Cox regression analysis was used to evaluate whether a clinical diagnosis of heart failure was associated with an increased risk of in-hospital and 30-day mortality while controlling for several potentially confounding prognostic factors. Variables included in the regression model were selected on the basis of the results of univariate analysis and a priori knowledge and included age, sex, body mass index, medical history (history of venous thromboembolism, chronic lung disease, diabetes, hypertension, ischemic heart disease, pulmonary hypertension, or chronic kidney disease), prior medication use (aspirin, statins, or warfarin), recent immobility, and type of venous thromboembolism on presentation (pulmonary embolism with or without deep vein thrombosis vs isolated deep vein thrombosis). All statistical analyses were performed using SAS version 9.2 (SAS Institute Inc, Cary, NC). RESULTS Baseline Characteristics Patients with heart failure who had venous thromboembolism were older than patients without heart failure (mean age 75.1 vs 62 years, P.0001) (Table 1). Patients with heart failure were more likely to develop venous thromboembolism during hospitalization for a non-venous thromboembolism-related condition (45.5% vs 23.8%, P.0001). Patients with heart failure with venous thromboembolism had a longer mean duration of hospitalization than those without heart failure (13.9 vs 7.9 days, P.0001). Comorbidities and Risk Factors Patients with heart failure and venous thromboembolism were more likely to have comorbid conditions of cerebrovascular disease (21.9% vs 9.9%, P.0001), chronic lung disease (38.9% vs 14%, P.0001), acute infectious illness (48% vs 21.2%, P.0001), chronic kidney disease (8.2% vs 1.5%, P.0001), and chronic venous insufficiency (11% vs 4.9%, P.0001) than patients without heart failure (Table 2). Patients with heart failure also were more likely to have manifestations of ischemic heart disease. Immobility was present in 65.2% of patients with heart failure compared with 46.1% of patients without heart failure (P.0001). Clinical Presentation of Venous Thromboembolism Presenting symptoms and signs of venous thromboembolism were similar among patients with and without heart failure (Table 3). Patients with heart failure were more likely to present with a lower mean hematocrit (34.5% vs 36.2%, P.0001) and a higher mean creatinine (1.57 vs 1.17 mg/dl, P.0001). Types of venous thromboembolism on presentation were similar except for upper-extremity deep vein thrombosis, which was more common among patients with heart failure (17.2% vs 12.3%, P.03). Patients with heart failure were more likely to have indwelling central venous catheters (33.5% vs 15.2%, P.0001). However, the proportion of patients with upper-extremity deep vein thrombosis and an indwelling central venous Table 1 Baseline Characteristics of Patients With Venous Thromboembolism Heart (n 319) No Heart (n 1503) P Value Age, y (mean SD) Age 65 y, 263 (82.5) 739 (49.2).0001 Body mass index, kg/m 2 (mean SD) Male, 127 (40.1) 689 (45.9).06 Female, 190 (59.9) 812 (54.1).06 Ethnicity, Caucasian 288 (90.3) 1347 (89.6).72 African-American 10 (3.1) 45 (3).89 Asian 0 (0) 4 (0.3) 1.0 Hispanic 8 (2.5) 35 (2.3).84 Other 5 (1.6) 11 (0.7).18 Developed venous thromboembolism during hospitalization 145 (45.5) 357 (23.8).0001 for another condition, Length of stay, d (mean SD) Length of stay 2 d, 69 (21.6) 506 (33.7).0001 SD standard deviation.

4 Piazza et al Venous Thromboembolism in Heart 255 Table 2 Comorbid Conditions in Patients With Venous Thromboembolism Heart No Heart P Value Hypertension, 253 (79.3) 706 (47).0001 Immobility 48 h, 208 (65.2) 693 (46.1).0001 Acute infectious illness, 153 (48) 318 (21.2).0001 Smoking history, Current smoker 47 (14.7) 298 (19.8).04 Former smoker 142 (44.5) 458 (30.5).0001 Never smoker 110 (34.5) 644 (42.9).006 Medication history, Aspirin 131 (41.1) 281 (18.7).0001 Statin 62 (19.4) 216 (14.4).02 Warfarin 49 (15.4) 121 (8.1).0001 Chronic lung disease, 124 (38.9) 210 (14).0001 Ischemic heart disease, ST-elevation myocardial infarction 7 (2.2) 9 (0.6).006 Non ST-elevation myocardial infarction 14 (4.4) 19 (1.3).0001 Unspecified myocardial infarction 91 (28.5) 1205 (8).0001 Any myocardial infarction 112 (35.1) 148 (9.9).0001 Unstable angina 36 (11.3) 41 (2.7).0001 Stable angina 53 (16.6) 65 (4.3).0001 Central venous catheter, 107 (33.5) 228 (15.2).0001 Intensive care unit discharge within the previous 3 mo, 106 (33.2) 190 (12.6).0001 Dyslipidemia, 104 (32.6) 329 (21.9).0001 Diabetes, 104 (32.6) 248 (16.5).0001 Cancer, 86 (27) 457 (30.4).22 Major surgery within the previous 3 mo, 83 (26) 412 (27.4).61 Endotracheal intubation within the previous 3 mo, 82 (25.7) 194 (12.9).0001 Previous negative evaluations for venous thromboembolism, 70 (21.9) 205 (13.6).0002 Cerebrovascular disease, 70 (21.9) 148 (9.9).0001 Cardiac procedure during admission, Catheterization or EP study 66 (20.7) 84 (5.6).0001 PCI and stent 20 (6.3) 39 (2.6).0008 Pacemaker 34 (10.7) 24 (1.6).0001 ICD implantation 12 (3.8) 4 (0.3).0001 Prior positive cardiac catheterization or PCI, 54 (16.9) 54 (3.6).0001 Peripheral artery disease, 52 (16.3) 75 (5).0001 Prior venous thromboembolism, 46 (14.4) 267 (17.8).15 Fracture, 46 (14.4) 146 (9.7).02 Prior coronary artery bypass surgery, 45 (14.1) 60 (4).0001 Chronic venous insufficiency, 35 (11) 74 (4.9).0001 Pulmonary hypertension, 34 (10.7) 22 (1.5).0001 Connective tissue disease, 28 (8.8) 56 (3.7).0001 Chronic kidney disease, 26 (8.2) 23 (1.5).0001 Dialysis dependent 20 (6.3) 23 (1.5).0001 Prior positive stress test, 21 (6.6) 24 (1.6).0001 Hormone replacement therapy, 14 (4.4) 111 (7.4).05 Hypercoagulable state, 4 (1.3) 29 (1.9).5 Oral contraceptive therapy, 0 (0) 38 (2.5).0009 EP electrophysiology; ICD implantable cardiac defibrillator; PCI percutaneous coronary intervention. catheter was similar among those with and without heart failure (68.8% vs 59.3%, P.23). Prophylaxis of Venous Thromboembolism Patients with heart failure who were hospitalized for any non-venous thromboembolism-related condition or who had major surgery within the 3 months before diagnosis of deep vein thrombosis or pulmonary embolism were more likely to have received prophylactic measures than patients without heart failure (68.9% vs 43.8%, P.0001) (Table 4). Patients with heart failure were more likely to have received prophylactic subcutaneous unfractionated heparin (37.4% vs 21.3%, P.0001), intravenous unfractionated heparin (15.7% vs 5%,

5 256 The American Journal of Medicine, Vol 124, No 3, March 2011 Table 3 Clinical Presentation of Venous Thromboembolism Heart No Heart P Value Extremity swelling, 155 (48.6) 682 (45.4).3 Extremity pain, 79 (24.8) 414 (27.5).31 Dyspnea, 71 (22.3) 267 (17.8).06 Hypoxemia (oxygen saturation 90%), 18 (21.2) 26 (13).08 Tachycardia (heart rate 100 beats/min), 33 (11.7) 148 (11.5).91 Cough, 31 (9.7) 92 (6.1).02 Fever, 30 (9.4) 88 (5.9).02 Chest pain, 25 (7.8) 108 (7.2).68 Hypotension (systolic blood pressure 100 mm Hg), 22 (7.8) 80 (6.2).32 Loss of consciousness, 7 (2.2) 13 (0.9).07 Dizziness, 4 (1.3) 23 (1.5) 1.0 Hemoptysis, 3 (0.9) 12 (0.8).74 Laboratory values Hematocrit, % (mean SD) Platelet count, platelets/mm 3 (mean SD) INR (mean SD) Creatinine, mg/dl (mean SD) Any deep vein thrombosis, 279 (87.5) 1313 (87.4).98 Proximal lower-extremity with calf deep vein thrombosis, 44 (15.8) 198 (15.1).77 Proximal lower-extremity without calf deep vein thrombosis, 135 (48.4) 631 (48.1).92 Pulmonary embolism, 90 (28.3) 380 (25.3).26 Pulmonary embolism and deep vein thrombosis, 51 (16) 191 (12.7).12 Upper-extremity deep vein thrombosis, 48 (17.2) 162 (12.3).03 Isolated calf deep vein thrombosis, 17 (6.1) 125 (9.5).07 SD standard deviation; INR international normalized ratio. P.0001), or pneumatic compression devices (40.6% vs 26.6%, P.0001). Treatment of Venous Thromboembolism Intravenous unfractionated heparin was the most common parenteral anticoagulant used in the initial treatment of venous thrombosis in patients with heart failure and patients Table 4 Characteristics of Prophylaxis in Patients With Hospitalization or Major Surgery Within 3 Months of Subsequently Developing Venous Thromboembolism* Heart No Heart P Value Receiving any prophylaxis, 197 (68.9) 538 (43.8).0001 Pneumatic compression 116 (40.6) 326 (26.6).0001 devices, SC unfractionated heparin, 107 (37.4) 261 (21.3).0001 IV unfractionated heparin, 45 (15.7) 61 (5).0001 LMWH, 22 (7.7) 91 (7.4).87 Warfarin, 21 (7.3) 57 (4.6).06 IV intravenous; LMWH low-molecular-weight heparin; SC subcutaneous. *Patients could have received 1 prophylactic modality. without heart failure (Table 5). Inferior vena cava filter placement was more common among patients with heart failure (16.3% vs 10.1%, P.001). Patients with heart failure were less likely to be prescribed low-molecularweight heparin as a bridge to therapeutic anticoagulation with warfarin at discharge (20.1% vs 31.9%, P.0001). Outcomes Patients with heart failure were more likely to have a complicated course after venous thromboembolism than patients without heart failure (Table 6). Although the frequency of in-hospital major bleeding was similar, patients with heart failure were more likely to present with long-term bleeding complications after treatment of venous thromboembolism (17.2% vs 11.4%, P.004). Patients with heart failure also were more likely to have in-hospital death (9.7% vs 3.3%, P.0001) and death within 30 days of the diagnosis of venous thromboembolism (15.6% vs 6.4%, P.0001), compared with patients without heart failures. History of heart failure was associated with a 2-fold increase in the risk of in-hospital death (adjusted odds ratio [OR] 2.04; 95% confidence interval [CI], ). Immobility was associated with a 4-fold increase in the rate of in-hospital death (adjusted OR 4.37; 95% CI, ), whereas presentation with pulmonary embolism as opposed to isolated deep vein thrombosis was associated with an approximately 5-fold increase in risk (adjusted OR 4.72; 95% CI, ). History of heart failure (adjusted OR 1.57; 95% CI, ), immo-

6 Piazza et al Venous Thromboembolism in Heart 257 Table 5 Therapy in Patients With Venous Thromboembolism* Heart No Heart P Value Initial Therapy Warfarin, 208 (65.2) 1130 (75.2).0002 IV unfractionated heparin, 178 (55.8) 733 (48.8).02 LMWH, 122 (38.2) 702 (46.7).006 Inferior vena cava filter, n 52 (16.3) 151 (10.1).001 (%) SC unfractionated heparin, 20 (6.3) 50 (3.3).01 Fibrinolysis of deep vein 7 (2.6) 19 (1.5).34 thrombosis/pulmonary embolism, Hirudin, 1 (0.3) 3 (0.2).54 Other parenteral 8 (2.5) 26 (1.7).36 anticoagulant, Discharge Therapy Warfarin alone, 126 (43.8) 611 (42.1).6 LMWH alone, 20 (6.9) 117 (8.1).52 LMWH and warfarin, 58 (20.1) 464 (31.9).0001 Neither, 84 (29.2) 261 (18).0001 IV intravenous; LMWH low-molecular-weight heparin; SC subcutaneous. *Patients could have received 1 therapeutic modality. bility (adjusted OR 3.05; 95% CI, ), and presentation with pulmonary embolism as opposed to isolated deep vein thrombosis (adjusted OR 1.83; 95% CI, ) also were independent predictors of death within 30 days of venous thromboembolism diagnosis. DISCUSSION We found that a history of heart failure among patients with venous thromboembolism was independently associated with a doubling of in-hospital death and an approximately 60% increase in the risk of death within 30 days. We observed not only high in-hospital mortality (9.7%) among patients with heart failure and venous thromboembolism but also substantial 30-day mortality (15.6%) among those in the community. Immobility is especially ominous among those with heart failure and is a potent predictor of both in-hospital mortality and death within 30 days of venous thromboembolism diagnosis. In our analysis of venous thromboembolism prophylaxis, we expected nearly all patients to receive preventive measures because of hospitalization for non-venous thromboembolism-related illness or major surgery within the previous 3 months. Although patients with heart failure had received venous thromboembolism prophylaxis more often than patients without heart failure, the rates were low in both groups. Our findings are consistent with other large registry analyses from Europe 8 and South America 9 in which patients with pulmonary embolism and heart failure were observed to have increased mortality in the outpatient setting. This increase in mortality among patients with heart failure may be attributable to inability to tolerate the hemodynamic and ventilatory demands of acute pulmonary embolism because of baseline pulmonary hypertension and right ventricular dysfunction. 13 In our analysis, we observed that presentation with pulmonary embolism as opposed to isolated deep vein thrombosis was associated with an increased risk of in-hospital mortality and death within 30 days of venous thromboembolism diagnosis. Comorbidities among patients with heart failure, such as chronic obstructive pulmonary disease, ischemic heart disease, and chronic kidney disease, further amplify the vulnerability of this population to complications of venous thromboembolism. Our study indicates that venous thromboembolism is an important source of in-hospital and outpatient mortality in the US population with heart failure. In a separate multicenter US Deep Vein Thrombosis registry of 5451 patients, we found patients with heart failure had high medical acuity with an increased frequency of comorbid conditions and risk factors contributing to the development of venous thromboembolism. These included immobility, acute infectious illness, chronic obstructive pulmonary disease, stroke, acute coronary syndrome, and chronic kidney disease. 14 In the current analysis, immobility contributed to a 4-fold increase in in-hospital mortality and an approximately 3-fold increase in death within 30 days of venous thromboembolism diagnosis. Other comorbidities in the current study, including chronic lung disease, ischemic heart disease, and chronic kidney disease, are known to increase the risk of venous thromboembolism but did not affect mortality. Other registry analyses have demonstrated similar findings regarding immobility. 7,8 These data demonstrate that strategies to reduce immobility and optimize heart failure therapy require further development. Table 6 Outcomes of Patients With Venous Thromboembolism Heart No Heart P Value No complications, 192 (60.2) 1031 (68.6).004 Recurrent pulmonary 15 (4.7) 81 (5.4).62 embolism,* Recurrent deep vein 37 (11.6) 243 (16.2).04 thrombosis,* Long-term major bleeding,* 55 (17.2) 171 (11.4).004 In-hospital major bleeding, 20 (6.3) 67 (4.5).17 Heparin-induced 8 (4.3) 13 (1.8).06 thrombocytopenia,* In-hospital death, 31 (9.7) 50 (3.3).0001 Death within 30 d of venous thromboembolism diagnosis, 49 (15.6) 94 (6.4).0001 *Long-term outcomes data encompassed a median follow-up period of 891 days (interquartile range days; maximum follow-up period 1095 days).

7 258 The American Journal of Medicine, Vol 124, No 3, March 2011 Despite published guidelines for the prevention of venous thromboembolism among patients with heart failure, 15 several registries that included large populations with heart failure have demonstrated that venous thromboembolism prophylaxis remains underused In particular, guidelines recommend that hospitalized patients with heart failure receive pharmacologic prophylaxis to prevent venous thromboembolism. 3 In the Acute Decompensated Heart National Registry, less than one third of eligible inpatients with heart failure received any venous thromboembolism prophylaxis. 20 Our present study is consistent with these data and emphasizes an unmet need for improving venous thromboembolism prophylaxis in this vulnerable patient population. Computerized or human 25 alert-based decision support strategies have the potential to improve venous thromboembolism prevention among acutely ill medical patients, including those with heart failure. Our findings must be interpreted in the context of the study design. The registry population was predominantly Caucasian, thereby limiting the ability to generalize these findings. The registry did not differentiate among systolic, diastolic, or a combined cause for heart failure and did not record data regarding left ventricular function. In addition, the registry did not record data regarding dose, frequency, or adequacy of thromboprophylaxis. As in any registry, unrecognized confounding may be present despite extensive evaluation of patient characteristics. The methodology used in this analysis is consistent with published criteria for evaluating the scientific value of clinical data registries. 26 Consecutive patients with objectively confirmed venous thromboembolism from urban, suburban, and rural communities were enrolled and represent a real world population. The use of clinical history of heart failure in lieu of left ventricular ejection fraction permitted the inclusion of patients with diastolic heart failure. CONCLUSIONS We observed high mortality among patients with heart failure and venous thromboembolism both during and after hospitalization. Heart failure and its commonly associated comorbidity of immobility are potent risk factors for inhospital death and death within 30 days in patients with venous thromboembolism. References 1. Spyropoulos AC, Hussein M, Lin J, Battleman D. Rates of venous thromboembolism occurrence in medical patients among the insured population. Thromb Haemost. 2009;102: Piazza G, Goldhaber SZ. Pulmonary embolism in heart failure. Circulation. 2008;118: Ng TM, Tsai F, Khatri N, et al. Venous thromboembolism in hospitalized patients with heart failure: incidence, prognosis, and prevention. Circ Heart Fail. 2010;3: Imberti D, Pierfranceschi MG, Falciani M, Prisco D. Venous thromboembolism prevention in patients with heart failure: an often neglected issue. Pathophysiol Haemost Thromb. 2008;36: Piazza G, Fanikos J, Zayaruzny M, Goldhaber SZ. Venous thromboembolic events in hospitalised medical patients. Thromb Haemost. 2009;102: Beemath A, Stein PD, Skaf E, et al. Risk of venous thromboembolism in patients hospitalized with heart failure. Am J Cardiol. 2006;98: Darze ES, Latado AL, Guimaraes AG, et al. Incidence and clinical predictors of pulmonary embolism in severe heart failure patients admitted to a coronary care unit. Chest. 2005;128: Monreal M, Munoz-Torrero JF, Naraine VS, et al. Pulmonary embolism in patients with chronic obstructive pulmonary disease or congestive heart failure. Am J Med. 2006;119: Darze ES, Latado AL, Guimaraes AG, et al. Acute pulmonary embolism is an independent predictor of adverse events in severe decompensated heart failure patients. Chest. 2007;131: Spencer FA, Emery C, Lessard D, et al. The Worcester Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med. 2006; 21: Spencer FA, Emery C, Lessard D, Goldberg RJ. Upper extremity deep vein thrombosis: a community-based perspective. Am J Med. 2007; 120: Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year populationbased study. Arch Intern Med. 1998;158: Piazza G, Goldhaber SZ. The acutely decompensated right ventricle: pathways for diagnosis and management. Chest. 2005;128: Piazza G, Seddighzadeh A, Goldhaber SZ. Heart failure in patients with deep vein thrombosis. Am J Cardiol. 2008;101: Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest. 2008;133:381S-453S. 16. Tapson VF, Decousus H, Pini M, et al. Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients: findings from the International Medical Prevention Registry on Venous Thromboembolism. Chest. 2007;132: Kahn SR, Panju A, Geerts W, et al. Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada. Thromb Res. 2007;119: Cohen AT, Tapson VF, Bergmann JF, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet. 2008;371: Amin A, Stemkowski S, Lin J, Yang G. Thromboprophylaxis rates in US medical centers: success or failure? J Thromb Haemost. 2007;5: Jois-Bilowich P, Michota F, Bartholomew JR, et al. Venous thromboembolism prophylaxis in hospitalized heart failure patients. J Card Fail. 2008;14: Piazza G, Goldhaber SZ. Computerized decision support for the cardiovascular clinician: applications for venous thromboembolism prevention and beyond. Circulation. 2009;120: Kucher N, Koo S, Quiroz R, et al. Electronic alerts to prevent venous thromboembolism among hospitalized patients. N Engl J Med. 2005; 352: Fiumara K, Piovella C, Hurwitz S, et al. Multi-screen electronic alerts to augment venous thromboembolism prophylaxis. Thromb Haemost. 2010;103: Baroletti S, Munz K, Sonis J, et al. Electronic alerts for hospitalized high-vte risk patients not receiving prophylaxis: a cohort study. J Thromb Thrombolysis. 2008;25: Piazza G, Rosenbaum EJ, Pendergast W, et al. Physician alerts to prevent symptomatic venous thromboembolism in hospitalized patients. Circulation. 2009;119: Alpert JS. 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8 Piazza et al Venous Thromboembolism in Heart 259 Appendix Criteria for Classification of Venous Thromboembolism Events* Deep vein thrombosis: Definite if confirmed by venography, compression ultrasonography, computed tomography, magnetic resonance imaging, or autopsy. Probable if the above tests were not performed, or were indeterminate, but impedence plethysmography, radionuclide venography, or radiolabeled fibrinogen scan test results were reported as positive. Possible if all of these confirmatory tests were not performed, or were indeterminate, and 2 of the following criteria were satisfied: the medical record indicated that the physician made a clinical diagnosis of deep vein thrombosis, symptoms or signs of deep vein thrombosis were documented, and the patient underwent therapy with anticoagulants or inferior vena cava filter insertion. Pulmonary embolism: Definite if confirmed by pulmonary angiography, spiral chest computed tomography, magnetic resonance imaging, or autopsy. Probable if the tests above were not performed, or were indeterminate, but ventilation-perfusion lung scan findings were high probability. Possible if all of the above confirmatory tests were not performed, or were indeterminate, and 2 of the following criteria were satisfied: the medical record indicated that the physician made a clinical diagnosis of pulmonary embolism, symptoms or signs of pulmonary embolism were documented, and the patient underwent therapy with anticoagulants or inferior vena cava filter insertion.) *Modified from criteria previously used by Silverstein et al 12 in the Olmstead County study of venous thromboembolism. Given increasing acceptance during the last decade of compression ultrasonography as a single diagnostic modality for deep vein thrombosis, we have classified patients with deep vein thrombosis confirmed by compression ultrasonography as definite, whereas these patients would have been categorized as probable by Silverstein et al s criteria.