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(Chest. 2005;128:2576-2580.)
© 2005 American College of Chest Physicians

Incidence and Clinical Predictors of Pulmonary Embolism in Severe Heart Failure Patients Admitted to a Coronary Care Unit*

Eduardo S. Darze, MD; Adriana L. Latado, MD; Aloyra G. Guimarães, MD; Rodrigo A. V. Guedes, MD; Alessandra B. Santos, MD; Simone S. de Moura, MD and Luiz Carlos S. Passos, MD, PhD

* From the Cardiology Division (Dr. Darze), Hospital Aliança, Salvador; and Coronary Care Unit (Drs. Latado, Guimarães, Guedes, Santos, de Moura, and Passos), Hospital Português, Salvador, Brazil.

Correspondence to: Eduardo S. Darze, MD, Cardiology Division, Echocardiography Laboratory, Hospital Aliança, Avenida Juracy Magalhães Jr., 2096, Salvador, BA, Brazil, 41920-000; e-mail: esdarze{at}ufba.br


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Objectives: To determine the incidence of clinical pulmonary embolism (PE) in a population with severe congestive heart failure (CHF) admitted to a coronary care unit (CCU), and to identify clinical predictors of PE in this population.

Design and setting: Prospective, observational study performed in a CCU of a tertiary care hospital between July 2001 and March 2003.

Patients: One hundred ninety-eight patients with severe decompensated CHF.

Measurements and results: Of 198 patients recruited, 18 patients (9.1%) received a diagnosis of PE during their hospitalization. Deep vein thrombosis was demonstrated in 8 of 18 patients (44.4%) with PE. Thromboprophylaxis was used by 12 of 18 patients (66.7%) with PE and 126 of 180 patients (70%) without PE (p = 0.77). Both groups were similar with respect to mean age (68.2 ± 14.1 years vs 69.6 ± 13.4 years [± SD]), proportion of male patients (61.1% vs 55.1%), markers of CHF severity (New York Heart Association functional class > II, ejection fraction < 30%, Na < 136 mEq/L, ischemic etiology), and comorbid conditions (diabetes mellitus, atrial fibrillation, chronic renal failure, hypertension) [p = not significant]. The presence of PE was significantly associated with cancer (relative risk [RR], 8.4; 95% confidence interval [CI], 3.9 to 18.1), immobilization (RR, 5.4; 95% CI, 2.0 to 14.4), previous venous thromboembolism (VTE) [RR, 4.4; 95% CI, 1.7 to 11.3], COPD (RR, 3.1; 95% CI, 1.03 to 9.2), and right ventricle (RV) abnormality (RR, 3.3; 95% CI, 1.3 to 8.0). In a multiple logistic regression analysis, only cancer (odds ratio [OR], 26.9; 95% CI, 4.9 to 146.8), RV abnormality (OR, 9.7; 95% CI, 2.2 to 42.6), and previous VTE (OR, 9.1; 95% CI, 1.28 to 64.7) remained independently associated with PE.

Conclusions: In patients with severe decompensated CHF admitted to a CCU, the incidence of clinical PE is very high despite adequate prophylaxis. Traditional risk factors seemed to play an important role in determining the risk of PE in this population.

Key Words: congestive heart failure • ICU • pulmonary embolism


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Venous thromboembolism (VTE) remains an important cause of morbidity and mortality in hospitalized nonsurgical patients.12 However, this is a very heterogeneous population with regards to the risk of VTE and bleeding complications, leading to a scattered and nonuniform use of prophylactic strategies.3

The publication of three large randomized trials456 has helped define the thromboembolic risk of hospitalized general medical patients. The incidence of VTE in the group of patients who received placebo was approximately 10%.46 In these studies, almost half of the patients enrolled had congestive heart failure (CHF) as their primary illness; within the placebo group, New York Heart Association (NYHA) class IV CHF patients had the highest incidence of VTE (21.7%).7 In fact, the severity of CHF appears to correlate with thromboembolic risk, with an ejection fraction < 20% being associated with a 38-fold increase in risk.8

Therefore, CHF patients represent not only a large proportion of hospitalized medical patients9 but also one of the highest risk categories for VTE.7 Additionally, randomized trials generally exclude the most critical CHF patients, who appear to be at an even higher risk of thromboembolic complications.10 The aims of this study were to determine the incidence of clinical pulmonary embolism (PE) in a population with severe CHF admitted to a coronary care unit (CCU), and to identify clinical predictors of PE in this population.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Patient Population
We prospectively enrolled 198 consecutive patients admitted to our CCU with a diagnosis of CHF between July 2001 and March 2003. After the evaluation by the on-call physician, two investigators reviewed the clinical data in order to ascertain the diagnosis of CHF before entering the study. Patients were excluded if they had an acute ST-segment elevation myocardial infarction and if they had a different admitting diagnosis despite having a history of CHF. All clinical and demographic data were collected directly from the patient, family member, attending physician, or the chart. The protocol was approved by the research ethics committee, and informed consent was obtained from all patients.

Definitions
Confirmed PE was defined as any level of clinical suspicion associated with the following: (1) high-probability lung scintigraphy findings,11 (2) positive findings on spiral CT of the chest, or (3) positive findings on conventional pulmonary angiography. Investigation for PE was initiated at the discretion of the attending physician. A total of 36 patients were investigated, and 18 patients had the diagnosis of PE confirmed. The other 18 patients had non–high-probability scans or negative chest CT findings. The only other imaging modality used in these patients was Doppler ultrasonography, and none had confirmed deep vein thrombosis. These patients were not included in the study.

Baseline functional status was assessed as NYHA class, 3 weeks prior to hospital admission. Right ventricular (RV) abnormality was defined as echocardiographically documented RV dilatation and/or systolic dysfunction. Cancer was considered as a potential risk factor if it had been treated within the last 6 months, or if the patient was receiving palliative care. Other potential risk factors were as follows: history of VTE, surgery within 1 month of presentation, inability to ambulate during the hospitalization period, obesity (body mass index > 30 kg/m2), and estrogen use. Effective VTE prophylaxis for medical patients was defined based on the American College of Chest Physicians consensus.12

Statistical Analysis
The comparisons between the groups with and without PE were performed using the unpaired Student t test for continuous variables and {chi}2 test for categorical variables. All values were expressed as mean ± SD or relative risk (RR) and its respective 95% confidence interval (CI).

A multiple logistic regression analysis was conducted in order to identify independent predictors of PE. Variables with significant bivariate associations or variables thought to be clinically important were included in a multivariate model. A p value < 0.05 was considered significant. Statistical analysis was performed using the statistical software (SPSS for Windows version 10; SPSS; Chicago, IL).


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
A total of 1,417 patients were admitted to our CCU during the study period. CHF was the admitting diagnosis in 223 patients, of whom 14 had an associated acute ST-segment elevation myocardial infarction and were excluded. After reviewing the clinical data, the investigators excluded 11 patients because the diagnosis of CHF was not confirmed. No patients declined to sign the consent form. Of 198 patients with severe CHF recruited to this study, 18 patients (9.1%) received a diagnosis of PE during their hospitalization period. The diagnosis of PE was confirmed by high-probability lung scintigraphy findings in 14 patients (78%) and positive spiral CT findings in 4 patients (22%). Doppler ultrasonography demonstrated deep vein thrombosis in 8 of 18 patients (44.4%), with PE involving the lower extremities (n = 7) and subclavian vein thrombosis (n = 1). In 67% of the patients with PE, the diagnosis was confirmed within 5 days of hospital admission.

Thromboprophylaxis was used by 12 of 18 patients (66.7%) with PE and 126 of 180 patients (70%) without PE (p = 0.77). All patients received enoxaparin, 40 mg qd, and none received unfractionated heparin or mechanical methods. There was no significant difference in the incidence of PE between patients who did or did not receive prophylaxis (8.7% vs 10%, p = 0.769). After the diagnosis, all patients received anticoagulation with therapeutic doses of heparin, and one patient received an inferior vena cava filter. The overall in-hospital mortality was 22.2% (44 of 198 patients), and the mean duration of hospital stay was 17.4 ± 26.2 days.

The overall population showed a high prevalence of traditionally recognized risk factors for VTE. At least one risk factor was present in 55 patients (27.8%), and half of these patients had two or more risk factors. However, risk factors were absent in 75.6% of patients without PE and in only 38.9% of patients with PE (Table 1 ).


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  		Table 1. Frequency of Risk Factors for VTE According to the Presence of PE*

 
The bivariate comparisons between the groups with and without PE are shown on Table 2 . The mean age (68.2 ± 14.1 years vs 69.6 ± 13.4 years) and weight (65.6 ± 14.5 kg vs 66.1 ± 14.2 kg) and the proportion of male patients (61.1% vs 55.1%) did not differ significantly (p = not significant). Markers of CHF severity (NYHA functional class > II, ejection fraction < 30%, Na < 136 mEq/L, ischemic etiology) and comorbid conditions (diabetes mellitus, atrial fibrillation, chronic renal failure, hypertension) were also equally frequent on both groups (p = not significant). The presence of PE was significantly associated with cancer (RR, 8.4; 95% CI, 3.9 to 18.1), immobilization (RR, 5.4; 95% CI, 2.0 to 14.4), previous VTE (RR, 4.4; 95% CI, 1.7 to 11.3), COPD (RR, 3.1; 95% CI, 1.03 to 9.2), and RV abnormality (RR, 3.3; 95% CI, 1.3 to 8.0). Multiple logistic regression analysis identified the following independent predictors of PE in this population (Table 3 ): cancer (odds ratio [OR], 26.9; 95% CI, 4.9 to 146.8), RV abnormality (OR, 9.7; 95% CI, 2.2 to 42.6), and previous VTE (OR, 9.1; 95% CI, 1.28 to 64.7).


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  		Table 2. Patient Characteristics According to the Presence of PE*

 

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  		Table 3. Multiple Logistic Regression Analysis

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The current study demonstrates a very high risk of PE in patients with severe decompensated CHF admitted to a CCU, despite adequate prophylaxis use by the majority of them. Additionally, traditional risk factors seemed to play an important role in determining the risk of PE in this population.

To the best of our knowledge, this is the first study to assess the incidence of PE and its clinical predictors in a very specific population with severe decompensated CHF. Knowledge of the thromboembolic risk and risk factors in specific groups of patients and clinical settings forms the basis for appropriate prophylaxis.

The high incidence of PE observed in this study can be attributed to the severity of the acute illness and the underlying disease, as well as the high index of suspicion maintained by the CCU physicians. CHF has been considered an important risk factor for VTE.7 Patients with CHF have abnormal levels of soluble P-selectin and von Willebrand factor, and high plasma viscosity, which, in association with venous stasis and decreased mobility, contribute to the hypercoagulable state induced by the disease.13 The levels of these markers of rheologic function (fibrinogen and plasma viscosity) are higher in more symptomatic patients (NYHA class III-IV).13 A case-control study8 of ambulatory patients has shown that CHF more than doubled the odds of VTE developing even after adjusting for confounding variables (OR, 2.6; 95% CI, 1.4 to 4,7). In the same study, the authors also demonstrated a progressive increase in the risk of VTE with worsening of the ejection fraction. In fact, NYHA class IV CHF patients seem to be the highest risk group for VTE among the hospitalized nonsurgical population.7 The population recruited in the current study consisted of patients with advanced CHF, with 55% being in NYHA III-IV at baseline, 40% having an ejection fraction < 30%, and with an in-hospital mortality of 22%. Also, all of them were treated in an ICU, a clinical setting associated with a high risk of VTE complications.14 An autopsy study15 revealed that 20% of patients who died in the ICU had evidence of PE. Therefore, our population is expected to be at high risk for PE because it comprises severe CHF patients who are critically ill. Our data, in addition to being clinically intuitive, are supported by other reports in the literature. In a study16 that recruited only CHF patients, the incidence of VTE was 46.7% in the placebo-treated study arm. More recently, in one of the largest medical ICUs studies,17 the incidence of symptomatic PE was 5%. In another study18 that analyzed the intracardiac electrogram of 119 patients with advanced CHF who died after having an implantable cardioverter defibrillator placed, PE was the cause of death in 5 patients (4.2%). This probably represents an underestimation of the incidence of fatal PE, given that the autopsy rate was only 15% and that the final rhythms were most commonly electromechanical dissociation and bradyarrhythmias, rhythms compatible with PE.18 Also contributing to the high incidence of PE in our study is the fact that our institution commonly serves as a recruiting center for international VTE studies, which heightens the suspicion of VTE on the part of our physicians.

The incidence of PE in our study was 9.1% despite the use of enoxaparin, 40 mg/d, by two thirds of the patients, which suggests that this strategy may be inadequate for this high-risk population. Some randomized trials19 in which the drugs are administered in a systematic and controlled fashion have shown that in spite of active prophylaxis, the incidence of VTE can be as high as 16% in high-risk patients. However, our data should be interpreted with caution since 67% of PE patients had their diagnosis confirmed within only 5 days of hospital admission, and PE could have actually developed before hospitalization. Additionally, data on prophylaxis were gathered from a review of physicians’ orders; therefore, the actual continuous use of the drug cannot be guaranteed.

Other studies have shown that traditionally recognized risk factors were equally prevalent in medical patients who did and did not have VTE.20 In contrary to these data, our study showed that cancer, previous VTE, and RV abnormalities were strong and independently associated with PE in this population. Of particular interest is the association between echocardiographically documented RV dilatation and/or dysfunction and the risk of PE. Although it has been suggested that PE patients who have RV dysfunction might be at increased risk for recurrence,21 the association between RV abnormality and subsequent PE in patients with CHF has not been reported previously. Although the sequence of events cannot be ascertained in this study, half of the PE patients who underwent echocardiography prior to the index admission already showed some degree of RV dysfunction (6 of 12 patients). Markers of CHF severity did not correlate significantly with the risk of PE. This is probably related to the fact that the population is homogeneously in an advanced stage of the disease, compromising the ability to detect subtle differences in the prevalence of these markers.

The diagnostic methods utilized in this study, lung scintigraphy and chest CT, are well validated for the diagnosis of PE.2223 Although the pretest clinical probability was not assessed, we do not believe it affected the conclusions of the study in any major way. The Prospective Investigation of Pulmonary Embolism Diagnosis study22 has shown that only 56% of patients with high-probability scan findings and low clinical probability actually had PE, questioning the specificity of the method when used without a pretest clinical probability. However, this exact combination of test result and clinical probability is very rare, occurring in only 1% of patients with suspected PE (9 of 887 patients)22 and therefore having very little impact on diagnostic accuracy in our study. In fact, the major problem with these diagnostic modalities is a relatively low sensitivity. Only 47% of patients with PE have a high-probability scan finding,22 and chest CT has serious problems in detecting emboli in subsegmental arteries.24 Therefore, it is possible that some of our patients with CHF may have had undiagnosed PE, which only reinforces the conclusion of this study that PE is a common complication in hospitalized CHF patients.

Prevention of VTE in hospitalized nonsurgical patients continuous to be a difficult challenge. Our data show that critically ill CHF patients are at very high risk for VTE complications despite "adequate" prophylaxis. The presence of traditional risk factors and RV dysfunction were strongly associated with the risk of these complications. More aggressive thromboprophylactic strategies, such as higher doses of low-molecular-weight heparin or combination of mechanical and pharmacologic methods, ought to be tested in this specific high-risk population.


   Footnotes
 
Abbreviations: CCU = coronary care unit; CHF = congestive heart failure; CI = confidence interval; NYHA = New York Heart Association; OR = odds ratio; PE = pulmonary embolism; RR = relative risk; RV = right ventricle/ventricular; VTE = venous thromboembolism

This work was performed at the Coronary Care Unit, Hospital Português, Salvador, Brazil.

Received for publication March 8, 2005. Accepted for publication April 26, 2005.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Rubinstein, I, Murray, D, Hoffstein, V (1988) Fatal pulmonary emboli in hospitalized patients: an autopsy study. Arch Intern Med 148,1425-1426[Abstract]
  2. Baglin, TP, White, K, Charles, A Fatal pulmonary embolism in hospitalized medical patients. J Clin Pathol 1997;50,609-618[Abstract/Free Full Text]
  3. Ageno, W, Squizzato, A, Ambrosini, F, et al Thrombosis prophylaxis in medical patients: a retrospective review of clinical practice patterns. Haematologica 2002;87,746-750[Abstract/Free Full Text]
  4. Samama, MM, Cohen, AT, Darmon, J-Y, et al A comparison of enoxaparin with placebo for the prevention of VTE in acutely ill medical patients. N Engl J Med 1999;341,793-800[Abstract/Free Full Text]
  5. Kleber, FX, Witt, C, Vogel, G, et al Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease. Am Heart J 2003;145,614-621[CrossRef][ISI][Medline]
  6. Leizorovicz, A, Cohen, AT, Turpie, AGG, et al Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004;110,874-879[CrossRef][ISI][Medline]
  7. Alikhan, R, Cohen, AT, Combe, S, et al Risk factors for venous thromboembolism in hospitalized patients with acute medical illness. Arch Intern Med 2004;164,963-968[Abstract/Free Full Text]
  8. Howell, MD, Geraci, JM, Knowlton, AA Congestive heart failure and outpatient risk of venous thromboembolism: a retrospective case-control study. J Clin Epidemiol 2001;54,810-816[CrossRef][ISI][Medline]
  9. Heart disease and stroke statistics, 2003 update. Dallas, TX: American Heart Association, 2002
  10. Cade, JF High risk of critically ill for VTE. Crit Care Med 1982;10,448-450[ISI][Medline]
  11. Miniati, M, Pistolesi, M, Marini, C, et al Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED). Am J Respir Crit Care Med 1996;154,1387-1393[Abstract]
  12. Geerts, WH, Pineo,, Heit, JA, et al Prevention of venous thromboembolism. Chest 2004;126,338S-400S[Abstract/Free Full Text]
  13. Gibbs, CR, Blann, AD, Watson, RDS, et al Abnormalities of hemorheological, endothelial, and platelet function in patients with chronic heart failure in sinus rhythm. Circulation 2001;103,1746-1751[ISI][Medline]
  14. Geerts, W, Selby, R Prevention of venous thromboembolism in the ICU. Chest 2003;124,357S-363S[Abstract/Free Full Text]
  15. Moser, KM, LeMoine, JR, Nachtwey, FJ, et al Deep venous thrombosis and pulmonary embolism: frequency in a respiratory intensive care unit. JAMA 1981;246,1422-1424[Abstract]
  16. Gallus, AS, Hirsh, J, Turttle, RJ, et al Small subcutaneous doses of heparin in the prevention of venous thrombosis. N Engl J Med 1973;288,545-551[ISI][Medline]
  17. Kapoor, M, Kupfer, YY, Tessler, S Subcutaneous heparin prophylaxis significantly reduces the incidence of venous thromboembolic events in the critically ill [abstract]. Crit Care Med 1999;27(suppl),A69
  18. Grubman, EM, Pavri, BB, Shipman, T, et al Cardiac death and stored electrograms in patients with third-generation implantable cardioverter-defibrillators. J Am Coll Cardiol 1998;32,1056-1062[Abstract/Free Full Text]
  19. Fraisse, F, Holzapfel, L, Coulaud, JM, et al Nadroparin in the prevention of deep vein thrombosis in acute decompensated COPD. Am J Respir Crit Care Med 2000;161,1109-1114[Abstract/Free Full Text]
  20. Hirsch, DR, Ingenito, EP, Goldhaber, SZ Prevalence of deep venous thrombosis among patients in medical intensive care. JAMA 1995;274,335-337[Abstract]
  21. Goldhaber, SZ, Haire, WD, Feldenstein, ML, et al Alteplase versus heparin in acute pulmonary embolism: randomized trial assessing right ventricular function and pulmonary perfusion. Lancet 1993;341,507-511[CrossRef][ISI][Medline]
  22. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). The PIOPED Investigators. JAMA 1990;263,2753-2759[Abstract]
  23. Hayashino, Y, Goto, M, Noguchi, Y, et al Ventilation-perfusion scanning and helical CT in suspected pulmonary embolism: meta-analysis of diagnostic performance. Radiology 2005;234,740-748[Abstract/Free Full Text]
  24. Van Strijen, MJ, De Monye, W, Kieft, GJ, et al Accuracy of single-detector spiral CT in the diagnosis of pulmonary embolism: a prospective multicenter cohort study of consecutive patients with abnormal perfusion scintigraphy. J Thromb Haemost 2005;3,17-28[CrossRef][ISI][Medline]




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