R F Gillum
Pulmonary embolism and thrombophlebitis in the United States, 1970-1985.
Am Heart J. 1987 Nov;114(5):1262-4.
Abstract/Text
A L Klatsky, M A Armstrong, J Poggi
Risk of pulmonary embolism and/or deep venous thrombosis in Asian-Americans.
Am J Cardiol. 2000 Jun 1;85(11):1334-7.
Abstract/Text
Several reports from Asian countries suggest a low prevalence of pulmonary embolism (PE) and deep venous thrombosis (DVT) in Asians, and sparse US data show that a slightly higher prevalence of PE/DVT in "nonwhites" than in whites is evident in all geographic regions except the Pacific region (California, Oregon, and Washington) where "nonwhites" include a larger proportion of Asians and Hispanics than in other US locations. We prospectively studied PE/DVT hospitalizations in 128,934 persons in relation to traits determined at health examinations in 1978 to 1985. Through 1994, 337 persons were subsequently hospitalized for PE and/or DVT (for PE first, n = 206). Cox proportional-hazards models with 9 covariates were used. In multivariate models, the following RRs (95% confidence intervals) were found for PE/DVT combined: black/white = 1.1 (0.4 to 1.4); Hispanic/white = 0.7 (0.3 to 1.5); and Asian/white = 0.2 (0.1 to 0. 5; p = 0.002). The lower risk of Asians was present in each sex and for persons first hospitalized for either PE or DVT. Covariates with significant positive relations to risk were age, male sex, body mass index, and a composite coronary disease risk/symptom variable; covariates not significantly related were education, marital status, smoking, and alcohol. These data suggest that Asians have very low risk of PE/DVT, which may account for US geographic variations in white/non-white risk differences. Possible explanations include the absence of hazardous mutations or unspecified PE/DVT protective traits in Asians.
Masahiro Ota, Mashio Nakamura, Norikazu Yamada, Takahiro Yazu, Ken Ishikura, Naoto Hiraoka, Hideki Tanaka, Hirofumi Fujioka, Naoki Isaka, Takeshi Nakano
Prognostic significance of early diagnosis in acute pulmonary thromboembolism with circulatory failure.
Heart Vessels. 2002 Nov;17(1):7-11. doi: 10.1007/s003800200036.
Abstract/Text
Despite the advances in our understanding of venous thromboembolic disease, the prevalence of pulmonary thromboembolism (PTE) at autopsy has not changed over 3 decades. When patients survive long enough to have a diagnosis of massive PTE and start receiving treatment, the outlook is considered to be moderately good. However, the diagnosis is often difficult to obtain and is frequently missed. We hypothesize that mortality of acute PTE is reduced by early diagnosis. Eighty-five patients with acute PTE with circulatory failure who survived 1 h after the onset were divided into two groups: the early Dx group consisted of the patients whose disease was diagnosed as acute PTE within 24 h of the onset, and the Late Dx group included patients whose disease was not diagnosed within 24 h of onset, or died without clinical diagnosis between 1 and 24 h after the onset. Overall mortality was significantly low in the Early Dx group compared with that of the Late Dx group (21.6% vs 67.6%, P < 0.0001). Multiple logistic regression analysis demonstrated that a reduction in in-hospital mortality was associated with early diagnosis (odds ratio for in-hospital death, 0.094; 95% confidence interval, 0.03-0.33). The results of our study suggested that early diagnosis might favorably affect the in-hospital clinical outcome of hemodynamically unstable patients with acute PTE.
Paul D Stein, Fadi Matta, Muzammil H Musani, Benjamin Diaczok
Silent pulmonary embolism in patients with deep venous thrombosis: a systematic review.
Am J Med. 2010 May;123(5):426-31. doi: 10.1016/j.amjmed.2009.09.037.
Abstract/Text
PURPOSE: To determine, by systematic review of the literature, the prevalence of silent pulmonary embolism in patients with deep venous thrombosis.
METHODS: Twenty-eight included published investigations were identified through PubMed. Studies were selected if methods of diagnosis of pulmonary embolism were described; if pulmonary embolism was stated to be asymptomatic; and if raw data were presented. Studies were stratified according to whether silent pulmonary embolism was diagnosed by a high-probability ventilation-perfusion lung scan using criteria from the Prospective Investigation of Pulmonary Embolism Diagnosis, computed tomography pulmonary angiography, or conventional pulmonary angiography (Tier 1), or by lung scans based on non-Prospective Investigation of Pulmonary Embolism Diagnosis criteria (Tier 2).
RESULTS: Silent pulmonary embolism was diagnosed in 1665 of 5233 patients (32%) with deep venous thrombosis. This is a conservative estimate because many of the investigations used stringent criteria for the diagnosis of pulmonary embolism. The incidence of silent pulmonary embolism was higher with proximal deep venous thrombosis than with distal deep venous thrombosis. Silent pulmonary embolism seemed to increase the risk of recurrent pulmonary embolism: 25 of 488 (5.1%) with silent pulmonary embolism versus 7 of 1093 (0.6%) without silent pulmonary embolism.
CONCLUSION: Silent pulmonary embolism sometimes involved central pulmonary arteries. Because approximately one third of patients with deep venous thrombosis have silent pulmonary embolism, routine screening for pulmonary embolism may be advantageous.
Copyright 2010 Elsevier Inc. All rights reserved.
Norikazu Yamada, Mashio Nakamura, Ken Ishikura, Masahiro Ota, Takahiro Yazu, Satoshi Ota, Masaaki Ito, Hirofumi Fujioka, Naoki Isaka, Takeshi Nakano
Triggers of acute pulmonary thromboembolism developed in hospital, with focusing on toilet activities as triggering acts.
Int J Cardiol. 2005 Feb 28;98(3):409-11. doi: 10.1016/j.ijcard.2003.12.014.
Abstract/Text
BACKGROUND: The recognition of the trigger which is the action leading to the occurrence of acute pulmonary thromboembolism (APTE) is important to perform early diagnosis and early management of APTE.
METHODS AND RESULTS: The trigger of APTE in 138 patients who developed APTE in hospital was investigated. The triggers of APTE were specified in 57 patients. Approximately half of these patients developed APTE during toilet activities (defecation and micturition). Mortality of the patients with APTE associated with toilet activities was 33%. APTE associated with toilet activities was independently related to a recent major surgery, heart diseases and a recent angiography.
CONCLUSIONS: Defecation and micturition would be common triggers of APTE after operation and angiography, especially in patients with cardiac dysfunction.
P Svensson, M Bakke, L Michler, L Arendt-Nielsen, E Møller
Trigeminal responses evoked by painful electrical stimulation.
J Oral Rehabil. 1998 Feb;25(2):128-34. doi: 10.1046/j.1365-2842.1998.00218.x.
Abstract/Text
Trigeminal sensory and motor responses to high-intensity electrical stimuli were studied in 10 healthy male subjects. During contraction at 10% of maximal bite force, late exteroceptive suppression periods assessed by EMG and bite force from masseter muscles were recorded together with evoked vertex potentials. Electrical stimuli were either delivered as 1 ms single pulses or as 21 ms (5 x 1 ms, 200 Hz) train pulses at two different intensities above the pain threshold. Three different perioral regions were stimulated in random order. The duration of the masseter suppression period was significantly longer and its latency significantly shorter at higher stimulus intensities whereas the amplitude of the evoked vertex potentials remained unchanged. Both the evoked potentials and the exteroceptive suppression period in the masseter muscle differed significantly between stimulation at the three perioral regions. The present results from combined measurements of sensory and motor responses in the trigeminal system may be explained by the function of trigeminal polysynaptic reflex circuits and the central cerebral processing of afferent inputs.
P D Stein, M L Terrin, C A Hales, H I Palevsky, H A Saltzman, B T Thompson, J G Weg
Clinical, laboratory, roentgenographic, and electrocardiographic findings in patients with acute pulmonary embolism and no pre-existing cardiac or pulmonary disease.
Chest. 1991 Sep;100(3):598-603.
Abstract/Text
The history, physical examination, chest radiograph, electrocardiogram and blood gases were evaluated in patients with suspected acute pulmonary embolism (PE) and no history or evidence of pre-existing cardiac or pulmonary disease. The investigation focused upon patients with no previous cardiac or pulmonary disease in order to evaluate the clinical characteristics that were due only to PE. Acute PE was present in 117 patients and PE was excluded in 248 patients. Among the patients with PE, dyspnea or tachypnea (greater than or equal to 20/min) was present in 105 of 117 (90 percent). Dyspnea, hemoptysis, or pleuritic pain was present in 107 of 117 (91 percent). The partial pressure of oxygen in arterial blood on room air was less than 80 mm Hg in 65 of 88 (74 percent). The alveolar-arterial oxygen gradient was greater than 20 mm Hg in 76 of 88 (86 percent). The chest radiograph was abnormal in 98 of 117 (84 percent). Atelectasis and/or pulmonary parenchymal abnormalities were most common, 79 of 117 (68 percent). Nonspecific ST segment or T wave change was the most common electrocardiographic abnormality, in 44 of 89 (49 percent). Dyspnea, tachypnea, or signs of deep venous thrombosis was present in 107 of 117 (91 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain was present in 113 of 117 (97 percent). Dyspnea or tachypnea or pleuritic pain or atelectasis or a parenchymal abnormality on the chest radiograph was present in 115 of 117 (98 percent). In conclusion, among the patients with pulmonary embolism that were identified, only a small percentage did not have these important manifestations or combinations of manifestations. Clinical evaluation, though nonspecific, is of considerable value in the selection of patients in whom there is a need for further diagnostic studies.
P D Stein, H A Saltzman, J G Weg
Clinical characteristics of patients with acute pulmonary embolism.
Am J Cardiol. 1991 Dec 15;68(17):1723-4.
Abstract/Text
Nils Kucher, Samuel Z Goldhaber
Management of massive pulmonary embolism.
Circulation. 2005 Jul 12;112(2):e28-32. doi: 10.1161/CIRCULATIONAHA.105.551374.
Abstract/Text
M Ghignone, L Girling, R M Prewitt
Volume expansion versus norepinephrine in treatment of a low cardiac output complicating an acute increase in right ventricular afterload in dogs.
Anesthesiology. 1984 Feb;60(2):132-5.
Abstract/Text
The authors investigated the effects of treatment on ventricular performance when cardiac output (CO) was reduced significantly because of an acute increase in pulmonary vascular resistance (PVR). In eight anesthetized, ventilated dogs, the effects of volume expansion (100 ml 6% dextran) on ventricular performance were determined before and after PVR was elevated. Resistance was increased by microembolization of the pulmonary vascular bed with glass beads (80-100 microns). When PVR was normal, volume expansion increased (P less than 0.05) stroke volume (SV) and mean blood pressure (BP). Alternatively, when RV afterload was increased, volume resulted in RV failure, i.e., decrease in SV (P less than 0.01) from 9.1 to 6.3 ml and a decrease (P less than 0.05) in mean BP from 97 to 65 mmHg, despite increased right ventricular end diastolic pressure (RVEDP) (P less than 0.05). Right ventricular dysfunction occurred with volume expansion, despite constant PVR and a decrease (P less than 0.01) in mean pulmonary artery pressure (PAP). In contrast to volume, norepinephrine infusion decreased biventricular filling pressures (P less than 0.01) and increased (P less than 0.01) SV from 6.2 to 11.3 ml. Accordingly, when RV afterload is increased significantly, even a relatively small increase in blood volume may result in RV dysfunction. Alternatively, inotropic agents with pressor effects may be the treatment of choice to increase CO when RV afterload is increased.
M Mathru, B Venus, R A Smith, Y Shirakawa, A Sugiura
Treatment of low cardiac output complicating acute pulmonary hypertension in normovolemic goats.
Crit Care Med. 1986 Feb;14(2):120-4.
Abstract/Text
In eight anesthetized ventilated goats, the hemodynamic effect of isoproterenol (ISU), dopamine (DOP), norepinephrine (NE), nitroglycerin (NTG), and Ringer's lactate (RL) infusion was evaluated after inducing acute pulmonary hypertension (PHN) to decrease cardiac output. Therapy with ISU significantly (p less than .05) increased cardiac output, but also increased transmural right ventricular end-diastolic pressure (RVEDPTM) and heart rate (HR) and decreased stroke volume (SV) and right ventricular ejection fraction (RVEF). NE increased cardiac output, mean arterial pressure (MAP), systemic vascular resistance (SVR), and RVEF. DOP decreased pulmonary vascular resistance (PVR) and increased cardiac output, MAP, and RVEF, but also significantly increased HR. NTG increased cardiac output and RVEF while decreasing SVR and PVR. Intravascular volume expansion by RL infusion increased cardiac output, SV, and RVEDPTM and decreased HR and PVR. The results of this study indicate that volume loading may be the treatment of choice to restore cardiac output in the face of acute PHN. NE and NTG may be effective as an adjunct therapy. Although ISU and DOP increase cardiac output, the concomitant elevation in HR is undesirable.
W D Molloy, K Y Lee, L Girling, U Schick, R M Prewitt
Treatment of shock in a canine model of pulmonary embolism.
Am Rev Respir Dis. 1984 Nov;130(5):870-4.
Abstract/Text
Despite the high mortality (greater than 30%) associated with hypotension complicating pulmonary embolism, previous studies have not systematically investigated how best to treat shock resulting from pulmonary embolism. In 24 dogs, we measured relevant hemodynamic parameters before and after shock was produced by intravenously injected autologous blood clots. When systemic blood pressure fell to 70 mmHg, dogs were randomly divided into groups and treated blindly for 1 h. All control dogs and all dogs treated with volume and isoproterenol died. In contrast, all dogs treated with noradrenaline were resuscitated and remained hemodynamically stable for 1 h. This effect of noradrenaline was significant (p less than 0.01, Fisher's exact test). Noradrenaline improved right ventricular performance by increasing blood pressure and improving right ventricular perfusion and/or by a direct increase in contractility. We conclude that in a canine model of pulmonary embolism and shock, noradrenaline may be the drug of choice for acute resuscitation.
Stavros V Konstantinides, Adam Torbicki, Giancarlo Agnelli, Nicolas Danchin, David Fitzmaurice, Nazzareno Galiè, J Simon R Gibbs, Menno V Huisman, Marc Humbert, Nils Kucher, Irene Lang, Mareike Lankeit, John Lekakis, Christoph Maack, Eckhard Mayer, Nicolas Meneveau, Arnaud Perrier, Piotr Pruszczyk, Lars H Rasmussen, Thomas H Schindler, Pavel Svitil, Anton Vonk Noordegraaf, Jose Luis Zamorano, Maurizio Zompatori, Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)
2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism.
Eur Heart J. 2014 Nov 14;35(43):3033-69, 3069a-3069k. doi: 10.1093/eurheartj/ehu283. Epub 2014 Aug 29.
Abstract/Text
Arne van Belle, Harry R Büller, Menno V Huisman, Peter M Huisman, Karin Kaasjager, Pieter W Kamphuisen, Mark H H Kramer, Marieke J H A Kruip, Johanna M Kwakkel-van Erp, Frank W G Leebeek, Mathilde Nijkeuter, Martin H Prins, Maaike Sohne, Lidwine W Tick, Christopher Study Investigators
Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography.
JAMA. 2006 Jan 11;295(2):172-9. doi: 10.1001/jama.295.2.172.
Abstract/Text
CONTEXT: Previous studies have evaluated the safety of relatively complex combinations of clinical decision rules and diagnostic tests in patients with suspected pulmonary embolism.
OBJECTIVE: To assess the clinical effectiveness of a simplified algorithm using a dichotomized clinical decision rule, D-dimer testing, and computed tomography (CT) in patients with suspected pulmonary embolism.
DESIGN, SETTING, AND PATIENTS: Prospective cohort study of consecutive patients with clinically suspected acute pulmonary embolism, conducted in 12 centers in the Netherlands from November 2002 through December 2004. The study population of 3306 patients included 82% outpatients and 57% women.
INTERVENTIONS: Patients were categorized as "pulmonary embolism unlikely" or "pulmonary embolism likely" using a dichotomized version of the Wells clinical decision rule. Patients classified as unlikely had D-dimer testing, and pulmonary embolism was considered excluded if the D-dimer test result was normal. All other patients underwent CT, and pulmonary embolism was considered present or excluded based on the results. Anticoagulants were withheld from patients classified as excluded, and all patients were followed up for 3 months.
MAIN OUTCOME MEASURE: Symptomatic or fatal venous thromboembolism (VTE) during 3-month follow-up.
RESULTS: Pulmonary embolism was classified as unlikely in 2206 patients (66.7%). The combination of pulmonary embolism unlikely and a normal D-dimer test result occurred in 1057 patients (32.0%), of whom 1028 were not treated with anticoagulants; subsequent nonfatal VTE occurred in 5 patients (0.5% [95% confidence interval {CI}, 0.2%-1.1%]). Computed tomography showed pulmonary embolism in 674 patients (20.4%). Computed tomography excluded pulmonary embolism in 1505 patients, of whom 1436 patients were not treated with anticoagulants; in these patients the 3-month incidence of VTE was 1.3% (95% CI, 0.7%-2.0%). Pulmonary embolism was considered a possible cause of death in 7 patients after a negative CT scan (0.5% [95% CI, 0.2%-1.0%]). The algorithm was completed and allowed a management decision in 97.9% of patients.
CONCLUSIONS: A diagnostic management strategy using a simple clinical decision rule, D-dimer testing, and CT is effective in the evaluation and management of patients with clinically suspected pulmonary embolism. Its use is associated with low risk for subsequent fatal and nonfatal VTE.
Isabelle Chagnon, Henri Bounameaux, Drahomir Aujesky, Pierre-Marie Roy, Anne-Laurence Gourdier, Jacques Cornuz, Thomas Perneger, Arnaud Perrier
Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism.
Am J Med. 2002 Sep;113(4):269-75. doi: 10.1016/s0002-9343(02)01212-3.
Abstract/Text
PURPOSE: Two prediction rules for pulmonary embolism have been described recently: the Wells' rule, which was derived from both outpatients and inpatients, and which includes a subjective element; and the Geneva rule, which is entirely standardized and is suitable only for emergency department patients. We compared the predictive accuracy and the concordance of the two methods, as well as the Geneva score overridden by implicit clinical judgment.
SUBJECTS AND METHODS: We studied 277 consecutive patients admitted to the emergency departments of three teaching hospitals. Clinical probability was assessed prospectively with the Geneva score and the Geneva score overridden by implicit clinical judgment in case of a disagreement. The Wells' score was calculated retrospectively.
RESULTS: The three methods classified similar proportions of patients as having a low (53% to 58% of patients), intermediate (37% to 41% of patients), or high (4% to 10% of patients) probability of pulmonary embolism. The actual frequencies of pulmonary embolism in each category were also similar (5% to 13% in the low, 38% to 40% in the intermediate, and 67% to 91% in the high clinical probability categories). Receiver operating characteristic curve analysis showed no difference between the two prediction rules, but the Geneva score overridden by implicit evaluation had a marginally higher accuracy. Concordance between the two prediction rules was fair (kappa coefficient = 0.43). Clinicians disagreed with the Geneva score in 21% of patients (n = 57).
CONCLUSIONS: The two prediction rules had a similar predictive accuracy for pulmonary embolism among emergency department patients. The Geneva rule appears to be more accurate when combined with clinical judgment, although it does not apply to inpatients.
P D Stein, S Z Goldhaber, J W Henry
Alveolar-arterial oxygen gradient in the assessment of acute pulmonary embolism.
Chest. 1995 Jan;107(1):139-43.
Abstract/Text
PURPOSE: The purpose of this investigation is to evaluate the utility of the alveolar-arterial (A-a) oxygen gradient in the diagnosis of acute pulmonary embolism (PE) among patients who participated in the Prospective Investigation of Pulmonary Embolism Diagnosis (PIO-PED).
METHODS: Pulmonary embolism was diagnosed (n = 280) or excluded (n = 499) by angiography in all patients. Patients were then categorized as (1) the entire cohort, (2) no prior cardiopulmonary disease and no prior PE, and (3) no prior PE or deep venous thrombosis. Normal values of the A-a gradient were defined in three ways: (1) values < or = 20 mm Hg; (2) values < or = age/4 + 4; and (3) values based on age from the literature.
RESULTS: When a normal A-a gradient was defined as < or = 20 mmHg, 11 to 14% of patients with PE in the three categories of patients had a normal A-a gradient. When the equation age/4 + 4 was used, 8% to 10% of patients with PE in the three categories of patients had a normal A-a gradient. With age-related values from the literature, 20 to 23% of patients with PE in the three categories of patients had a normal A-a gradient. The A-a gradient was normal in comparable percentages of patients who did not have PE.
CONCLUSION: Normal values of the A-a gradient did not exclude the diagnosis of acute PE.
P D Stein, S Z Goldhaber, J W Henry, A C Miller
Arterial blood gas analysis in the assessment of suspected acute pulmonary embolism.
Chest. 1996 Jan;109(1):78-81.
Abstract/Text
PURPOSE: The utility of arterial blood gas levels in excluding the diagnosis of acute pulmonary embolism (PE) was evaluated.
METHODS: Data are from the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED). PE was diagnosed or excluded by pulmonary angiography. Among 330 patients with no prior cardiopulmonary disease, 130 patients had PE and 200 did not. Among 438 patients with prior cardiopulmonary disease, 147 had PE and 291 did not. Definitions were low PaO2 (< 80 mm Hg), low PaCO2 (< 35 mm Hg), and high alveolar-arterial oxygen gradient (P(A-a)O2 [> 20 mm Hg]).
RESULTS: Among patients with no prior cardiopulmonary disease who had values of the PaO2 and PaCO2 that were not low and a P(A-a)O2 that was normal, 16 of 42 or 38% (95% confidence interval [CI] = 24 to 54%) had PE. Among patients with prior cardiopulmonary disease who had PaO2 and PaCO2 values that were not low and a P(A-a)O2 that was normal, 4 of 28 or 14% (95% CI = 4 to 33%) had PE. Other combinations of blood gas levels and the P(A-a)O2 gradient, failed to exclude PE in larger percentages of patients.
CONCLUSION: With various combinations of the PaO2 of 80 mm Hg or more, the PaCO2 of 35 mm Hg or higher, and the P(A-a)O2 gradient of 20 mm Hg or less, PE could not be excluded in more than 30% of patients with no prior cardiopulmonary disease and PE could not be excluded in more than 14% of patients with prior cardiopulmonary disease. Blood gas levels, therefore, are of insufficient discriminant value to permit exclusion of the diagnosis of PE.
Paul D Stein, Russell D Hull, Kalpesh C Patel, Ronald E Olson, William A Ghali, Rollin Brant, Rita K Biel, Vinay Bharadia, Neeraj K Kalra
D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review.
Ann Intern Med. 2004 Apr 20;140(8):589-602.
Abstract/Text
BACKGROUND: Despite extensive literature, the diagnostic role of d-dimer for deep venous thrombosis (DVT) or pulmonary embolism (PE) remains unclear, reflecting multiple d-dimer assays and concerns about differing sensitivities and variability.
PURPOSE: To systematically review trials that assessed sensitivity, specificity, likelihood ratios, and variability among d-dimer assays.
DATA SOURCES: Studies in all languages were identified by searching PubMed from 1983 to January 2003 and EMBASE from 1988 to January 2003.
STUDY SELECTION: The researchers selected prospective studies that compared d-dimer with a reference standard. Studies of high methodologic quality were included in the primary analyses; sensitivity analysis included additional weaker studies.
DATA EXTRACTION: Two authors collected data on study-level factors: d-dimer assay used, cutoff value, and whether patients had suspected DVT or PE.
DATA SYNTHESIS: For DVT, the enzyme-linked immunosorbent assay (ELISA) and quantitative rapid ELISA dominate the rank order for these values: sensitivity, 0.96 (95% confidence limit [CL], 0.91 to 1.00), and negative likelihood ratio, 0.12 (CL, 0.04 to 0.33); and sensitivity, 0.96 (CL, 0.90 to 1.00), and negative likelihood ratio, 0.09 (CL, 0.02 to 0.41), respectively. For PE, the ELISA and quantitative rapid ELISA also dominate the rank order for these values: sensitivity, 0.95 (CL, 0.85 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.03 to 0.58); and sensitivity, 0.95 (CL, 0.83 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.02 to 0.84), respectively. The ELISA and quantitative rapid ELISA have negative likelihood ratios that yield a high certainty for excluding DVT or PE. The positive likelihood values, which are in the general range of 1.5 to 2.5, do not greatly increase the certainty of diagnosis. Sensitivity analyses do not affect these findings.
LIMITATIONS: Although many studies evaluated multiple d-dimer assays, findings are based largely on indirect comparisons of test performance characteristics across studies.
CONCLUSION: The ELISAs in general dominate the comparative ranking among the d-dimer assays for sensitivity and negative likelihood ratio. For excluding PE or DVT, a negative result on quantitative rapid ELISA is as diagnostically useful as a normal lung scan or negative duplex ultrasonography finding.
Marc Righini, Josien Van Es, Paul L Den Exter, Pierre-Marie Roy, Franck Verschuren, Alexandre Ghuysen, Olivier T Rutschmann, Olivier Sanchez, Morgan Jaffrelot, Albert Trinh-Duc, Catherine Le Gall, Farès Moustafa, Alessandra Principe, Anja A Van Houten, Marije Ten Wolde, Renée A Douma, Germa Hazelaar, Petra M G Erkens, Klaas W Van Kralingen, Marco J J H Grootenboers, Marc F Durian, Y Whitney Cheung, Guy Meyer, Henri Bounameaux, Menno V Huisman, Pieter W Kamphuisen, Grégoire Le Gal
Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study.
JAMA. 2014 Mar 19;311(11):1117-24. doi: 10.1001/jama.2014.2135.
Abstract/Text
IMPORTANCE: D-dimer measurement is an important step in the diagnostic strategy of clinically suspected acute pulmonary embolism (PE), but its clinical usefulness is limited in elderly patients.
OBJECTIVE: To prospectively validate whether an age-adjusted D-dimer cutoff, defined as age × 10 in patients 50 years or older, is associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE.
DESIGN, SETTINGS, AND PATIENTS: A multicenter, multinational, prospective management outcome study in 19 centers in Belgium, France, the Netherlands, and Switzerland between January 1, 2010, and February 28, 2013.
INTERVENTIONS: All consecutive outpatients who presented to the emergency department with clinically suspected PE were assessed by a sequential diagnostic strategy based on the clinical probability assessed using either the simplified, revised Geneva score or the 2-level Wells score for PE; highly sensitive D-dimer measurement; and computed tomography pulmonary angiography (CTPA). Patients with a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff did not undergo CTPA and were left untreated and formally followed-up for a 3-month period.
MAIN OUTCOMES AND MEASURES: The primary outcome was the failure rate of the diagnostic strategy, defined as adjudicated thromboembolic events during the 3-month follow-up period among patients not treated with anticoagulants on the basis of a negative age-adjusted D-dimer cutoff result.
RESULTS: Of the 3346 patients with suspected PE included, the prevalence of PE was 19%. Among the 2898 patients with a nonhigh or an unlikely clinical probability, 817 patients (28.2%) had a D-dimer level lower than 500 µg/L (95% CI, 26.6%-29.9%) and 337 patients (11.6%) had a D-dimer between 500 µg/L and their age-adjusted cutoff (95% CI, 10.5%-12.9%). The 3-month failure rate in patients with a D-dimer level higher than 500 µg/L but below the age-adjusted cutoff was 1 of 331 patients (0.3% [95% CI, 0.1%-1.7%]). Among the 766 patients 75 years or older, of whom 673 had a nonhigh clinical probability, using the age-adjusted cutoff instead of the 500 µg/L cutoff increased the proportion of patients in whom PE could be excluded on the basis of D-dimer from 43 of 673 patients (6.4% [95% CI, 4.8%-8.5%) to 200 of 673 patients (29.7% [95% CI, 26.4%-33.3%), without any additional false-negative findings.
CONCLUSIONS AND RELEVANCE: Compared with a fixed D-dimer cutoff of 500 µg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01134068.
Paul D Stein, Pamela K Woodard, John G Weg, Thomas W Wakefield, Victor F Tapson, H Dirk Sostman, Thomas A Sos, Deborah A Quinn, Kenneth V Leeper, Russell D Hull, Charles A Hales, Alexander Gottschalk, Lawrence R Goodman, Sarah E Fowler, John D Buckley, PIOPED II investigators
Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators.
Am J Med. 2006 Dec;119(12):1048-55. doi: 10.1016/j.amjmed.2006.05.060.
Abstract/Text
PURPOSE: To formulate comprehensive recommendations for the diagnostic approach to patients with suspected pulmonary embolism, based on randomized trials.
METHODS: Diagnostic management recommendations were formulated based on results of the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) and outcome studies.
RESULTS: The PIOPED II investigators recommend stratification of all patients with suspected pulmonary embolism according to an objective clinical probability assessment. D-dimer should be measured by the quantitative rapid enzyme-linked immunosorbent assay (ELISA), and the combination of a negative D-dimer with a low or moderate clinical probability can safely exclude pulmonary embolism in many patients. If pulmonary embolism is not excluded, contrast-enhanced computed tomographic pulmonary angiography (CT angiography) in combination with venous phase imaging (CT venography), is recommended by most PIOPED II investigators, although CT angiography plus clinical assessment is an option. In pregnant women, ventilation/perfusion scans are recommended by many as the first imaging test following D-dimer and perhaps venous ultrasound. In patients with discordant findings of clinical assessment and CT angiograms or CT angiogram/CT venogram, further evaluation may be necessary.
CONCLUSION: The sequence for diagnostic test in patients with suspected pulmonary embolism depends on the clinical circumstances.
Clive Kearon, Jeffrey S Ginsberg, James Douketis, Alexander G Turpie, Shannon M Bates, Agnes Y Lee, Mark A Crowther, Jeffrey I Weitz, Patrick Brill-Edwards, Philip Wells, David R Anderson, Michael J Kovacs, Lori-Ann Linkins, Jim A Julian, Laura R Bonilla, Michael Gent, Canadian Pulmonary Embolism Diagnosis Study (CANPEDS) Group
An evaluation of D-dimer in the diagnosis of pulmonary embolism: a randomized trial.
Ann Intern Med. 2006 Jun 6;144(11):812-21.
Abstract/Text
BACKGROUND: It may be safe to omit additional diagnostic testing in selected patients with suspected pulmonary embolism (PE) who have a negative D-dimer test, but this approach has never been evaluated in a randomized, controlled trial.
OBJECTIVE: To determine if additional diagnostic testing can be safely withheld in patients with suspected PE who have negative erythrocyte agglutination D-dimer test results.
DESIGN: Randomized comparisons in 2 subgroups of a prospective multicenter study.
SETTING: 7 university hospitals.
PATIENTS: 1126 outpatients or inpatients with suspected PE; of these, 456 patients with negative erythrocyte agglutination D-dimer test results were randomly assigned to the intervention groups. Patients were classified into 2 clinical probability groups: those with a low clinical probability of PE (low-probability group) and those with a moderate or high clinical probability of PE, a nondiagnostic ventilation-perfusion lung scan, and no evidence of proximal deep venous thrombosis on bilateral ultrasonography (moderate- or high-probability group).
INTERVENTIONS: The experimental intervention for both probability groups was no further diagnostic testing for PE. The control intervention for the low-probability group was a ventilation-perfusion lung scan followed by ultrasonography of the proximal deep veins of the legs on the same day. If the lung scan was nondiagnostic, ultrasonography of the legs was repeated 7 and 14 days later. The control intervention for the moderate- or high-probability group was ultrasonography of the proximal deep veins of the legs after 7 and 14 days. In the control and experimental groups, anticoagulation was withheld or withdrawn if PE was not diagnosed.
MEASUREMENTS: Symptomatic venous thromboembolism (VTE) during 6 months of follow-up.
RESULTS: Prevalence of VTE was 15.2% in the 1126 enrolled patients. In the low-probability group, VTE occurred during follow-up in 0 of 182 patients who had no additional diagnostic testing and in 1 of 185 patients who had additional testing (difference, -0.5 percentage point [95% CI, -3.0 to 1.6 percentage points]). In the moderate- or high-probability group, VTE occurred during follow-up in 1 of 41 patients who had no additional diagnostic testing and in 0 of 41 patients who had additional testing (difference, 2.4 percentage points [CI, -6.4 to 12.6 percentage points]).
LIMITATIONS: The authors could not enroll 2000 patients as originally planned; 3 randomly assigned patients did not receive the allocated intervention, and 7 received inadequate follow-up. Personnel who performed follow-up evaluations were not blinded to the results of diagnostic testing at enrollment or to allocation group assignments.
CONCLUSION: In patients with a low probability of PE who have negative D-dimer results, additional diagnostic testing can be withheld without increasing the frequency of VTE during follow-up. Low clinical probability and negative D-dimer results occur in 50% of outpatients and in 20% of inpatients with suspected PE.
Guidelines on diagnosis and management of acute pulmonary embolism. Task Force on Pulmonary Embolism, European Society of Cardiology.
Eur Heart J. 2000 Aug;21(16):1301-36. doi: 10.1053/euhj.2000.2250.
Abstract/Text
M A Crowther, D J Cook, L E Griffith, M Meade, S Hanna, C Rabbat, S M Bates, W Geerts, M Johnston, G Guyatt
Neither baseline tests of molecular hypercoagulability nor D-dimer levels predict deep venous thrombosis in critically ill medical-surgical patients.
Intensive Care Med. 2005 Jan;31(1):48-55. doi: 10.1007/s00134-004-2467-2. Epub 2004 Dec 9.
Abstract/Text
OBJECTIVE: Predicting patients who are harboring asymptomatic deep venous thrombosis (DVT), or who are at particular risk of developing DVT, is a desirable clinical goal since prevention or early treatment of DVT might reduce the risk of fatal pulmonary embolism. Thus validation of simple laboratory tests that reliably predict venous thromboembolism (VTE) would be clinically very important. Tests that might be useful for these applications include markers of hypercoagulability (predicting patients at risk of DVT) and D-dimer (predicting which patients may have acute DVT).
METHODS: In a prospective cohort study we measured a panel of hypercoagulability markers at the time of ICU admission, and six commercial D-dimer assays were performed serially during the ICU stay in medical-surgical ICU patients who were screened for DVT with biweekly lower limb compression ultrasonography. Ultrasonography was also performed at the time of any clinically suspected DVT events. We matched cases with DVT with controls without DVT for length of stay in the ICU to generate receiver operating characteristics (ROC) curves.
RESULTS: One hundred ninety-seven patients were enrolled. Blood was collected on a total of 763 occasions (median number of occasions per patient: 3, range 1-21). None of the assays predicted DVT, as indicated by the areas under the ROC curves, that did not differ significantly from 50%.
CONCLUSION: In critically ill patients, neither tests of hypercoagulability nor D-dimer levels predict patients at risk of DVT and thus they should not be used to guide diagnostic testing for DVT.
Suman W Rathbun, Thomas L Whitsett, Sara K Vesely, Gary E Raskob
Clinical utility of D-dimer in patients with suspected pulmonary embolism and nondiagnostic lung scans or negative CT findings.
Chest. 2004 Mar;125(3):851-5.
Abstract/Text
BACKGROUND: The diagnosis of pulmonary embolism is difficult because the clinical diagnosis is nonspecific and all of the objective tests have limitations. The assay for plasma d-dimer may be useful as an exclusion test if results are negative. We conducted a prospective cohort study that evaluated the clinical utility (usefulness) of an automated quantitative d-dimer test in the diagnosis of patients with suspected pulmonary embolism.
METHODS: Consecutive eligible patients who had clinically suspected PE with nondiagnostic lung scans or negative helical CT scan of the chest results underwent d-dimer testing.
RESULTS: The d-dimer results were negative in 11 of 103 inpatients (10.6%, 95% confidence interval [CI], 5.5 to 18.3%) and 7 of 22 outpatients (31.8%, 95% CI, 13.9 to 54.9%; p = 0.02).
CONCLUSIONS: Measurement of plasma d-dimer is of limited clinical utility for inpatients with clinically suspected pulmonary embolism and nondiagnostic lung scans or negative helical CT results at a US academic health center.
Reza Karami-Djurabi, Frederikus A Klok, Judith Kooiman, Sophie I Velthuis, Mathilde Nijkeuter, Menno V Huisman
D-dimer testing in patients with suspected pulmonary embolism and impaired renal function.
Am J Med. 2009 Nov;122(11):1050-3. doi: 10.1016/j.amjmed.2009.03.032. Epub 2009 Aug 19.
Abstract/Text
BACKGROUND: Determination of pretest probability and D-dimer tests are the first diagnostic steps in patients with suspected pulmonary embolism, which can be ruled out when clinical probability is unlikely and D-dimer level is normal. We evaluated the utility of D-dimer testing in patients with impaired renal function.
METHODS: D-dimer tests were performed in consecutive patients with suspected pulmonary embolism and an unlikely clinical probability. Creatinine levels were assessed as clinical routine. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula. Correlation between D-dimer level and renal function and proportions of patients with normal D-dimer in different categories of estimated glomerular filtration rate (eGFR) were assessed. Different categories of decreasing eGFR were defined as: normal renal function (eGFR >89 mL/min), mild decrease in eGFR (eGFR 60-89 mL/min), and moderate decrease in eGFR (eGFR 30-59 mL/min).
RESULTS: Creatinine levels were assessed in 351 of 385 patients (91%). D-dimer levels significantly increased in 3 categories of decreasing eGFR (P = .027 and P = .021 for moderate renal impairment compared with mild renal impairment and normal renal function, respectively). Normal D-dimer levels were found in 58% of patients with eGFR >89 mL/min, in 54% with eGFR 60-89 mL/min, and in 28% with eGFR 30-59 mL/min.
CONCLUSIONS: The specificity of D-dimer testing in patients with suspected pulmonary embolism and decreased GFR is significantly decreased. Nonetheless, performing D-dimer tests is still useful because computed tomography scanning can be withheld in a significant proportion of these patients.
M Righini, C Goehring, H Bounameaux, A Perrier
Effects of age on the performance of common diagnostic tests for pulmonary embolism.
Am J Med. 2000 Oct 1;109(5):357-61.
Abstract/Text
PURPOSE: The diagnosis of pulmonary embolism in the elderly is often difficult because of comorbid medical conditions, and perhaps also because diagnostic tests have a lower yield. We analyzed the diagnostic performance of common diagnostic tests for pulmonary embolism in different age groups.
METHODS: We analyzed data from two large studies that enrolled 1,029 consecutive patients presenting to the emergency department with clinically suspected pulmonary embolism. The clinical probability of pulmonary embolism (high [>/=80%], intermediate, or low [RESULTS: The prevalence of pulmonary embolism increased progressively, from 12% in patients <40 years of age to 44% in those >/=80 years of age. The positive predictive value of a high clinical probability of pulmonary embolism was greater in the elderly (71% to 78% in those >/=60 years old versus 40% to 64% in those /=80 years old. The diagnostic yield of lower limb compression ultrasonography was greater in the elderly. The proportion of lung scans that were diagnostic (normal, near-normal, or high probability) decreased from 68% to 42% with increasing age.
CONCLUSIONS: Age affects the performance of common diagnostic tests for pulmonary embolism and should be kept in mind when evaluating patients suspected of having this condition.
R J Panos, R A Barish, D W Whye, G Groleau
The electrocardiographic manifestations of pulmonary embolism.
J Emerg Med. 1988 Jul-Aug;6(4):301-7.
Abstract/Text
The electrocardiographic manifestations of pulmonary embolism include rhythm and condition disturbances and changes in the P wave, QRS complex, or T wave. Since these abnormalities are highly variable and frequently transient, they lack the sensitivity necessary to establish the diagnosis of pulmonary embolism. The electrocardiogram may rise the suspicion of pulmonary embolism, but other diagnostic tests are necessary to confirm the diagnosis.
M D Thames, J S Alpert, J E Dalen
Syncope in patients with pulmonary embolism.
JAMA. 1977 Dec 5;238(23):2509-11.
Abstract/Text
A review of 132 consecutive cases of acute pulmonary embolism (PE) documented by pulmonary angiography indicated that syncope was the initial or predominant clinical feature in 17 (13%). When massive PE causes syncope in a nonhospitalized patient, the diagnosis of PE is frequently overlooked. Hypotension after PE may resolve spontaneously after a short interval. In this circumstance, the syncopal episode might easily be attributed to another cause. The appropriate diagnosis can be established only if other clues, suggestive of PE, are sought. Both arterial blood gas determinations and pulmonary scintigraphy are helpful in making this diagnosis.
A Geibel, M Zehender, W Kasper, M Olschewski, C Klima, S V Konstantinides
Prognostic value of the ECG on admission in patients with acute major pulmonary embolism.
Eur Respir J. 2005 May;25(5):843-8. doi: 10.1183/09031936.05.00119704.
Abstract/Text
A number of ECG abnormalities can be observed in the acute phase of pulmonary embolism (PE). Their prognostic value has not yet been systematically studied in large patient populations. In 508 patients with acute major PE derived from a large prospective registry, the current authors assessed, on admission, the impact of specific pathological ECG findings on early (30-day) mortality. Atrial arrhythmias, complete right bundle branch block, peripheral low voltage, pseudoinfarction pattern (Q waves) in leads III and aVF, and ST segment changes (elevation or depression) over the left precordial leads, were all significantly more frequent in patients with a fatal outcome. Overall, 29% of the patients who exhibited at least one of these abnormalities on admission did not survive to hospital discharge, as opposed to only 11% of the patients without a pathological 12-lead ECG. Multivariate analysis revealed that the presence of at least one of the above ECG findings was, besides haemodynamic instability, syncope and pre-existing chronic pulmonary disease, a significant independent predictor of outcome. In conclusion, ECG may be a useful, simple, non-costly tool for initial risk stratification of patients with acute major pulmonary embolism.
E Ferrari, A Imbert, T Chevalier, A Mihoubi, P Morand, M Baudouy
The ECG in pulmonary embolism. Predictive value of negative T waves in precordial leads--80 case reports.
Chest. 1997 Mar;111(3):537-43.
Abstract/Text
BACKGROUND AND STUDY OBJECTIVE: The value of the ECG for the diagnosis of pulmonary embolism (PE) is debatable. Once the diagnosis of PE has been established, however, the ECG could allow the massive forms to be distinguished. The purpose of our study was to analyze the ECG signs in patients hospitalized for PE in a cardiology unit.
DESIGN: Taking a series of 80 consecutive patients hospitalized for PE, we analyzed the ECGs on admission and then during hospitalization. We sought to evaluate changes in ECG signs compared with angiographic and hemodynamic changes in PE.
RESULTS: T-wave inversion in the precordial leads is the most common abnormality (68%), and represents the ECG sign best correlated to the severity of the PE. Among those patients with anterior T-wave inversion, 90% had a Miller index over 50% (mean, 60 +/- 8%). Eighty-one percent had a mean pulmonary arterial pressure (PAP) over 30 mm Hg (mean, 37 +/- 8%). This subepicardial ischemic pattern is an even stronger marker of severity when it appears as early as the first day (p < 0.01). Its reversibility is correlated to the changes in PE. After thrombolysis in particular, normalization of repolarization systematically indicates mean Miller and PAP indexes of < 20% and < 20 mm Hg, respectively.
CONCLUSIONS: The anterior subepicardial ischemic pattern is the most frequent ECG sign of massive PE. This parameter is easy to obtain and reflects the severity of PE. Its reversibility before the sixth day points to a good outcome or high level of therapeutic efficacy.
C G Elliott, S Z Goldhaber, L Visani, M DeRosa
Chest radiographs in acute pulmonary embolism. Results from the International Cooperative Pulmonary Embolism Registry.
Chest. 2000 Jul;118(1):33-8.
Abstract/Text
OBJECTIVES: To characterize chest radiographic interpretations in a large population of patients who have received a diagnosis of acute pulmonary embolism and to estimate the sensitivity and specificity of chest radiographic abnormalities for right ventricular hypokinesis that has been diagnosed by echocardiography.
DESIGN: A prospective observational study at 52 hospitals in seven countries.
PATIENTS: A total of 2,454 consecutive patients who had received a diagnosis of acute pulmonary embolism between January 1995 and November 1996.
RESULTS: Chest radiographs were available for 2,322 patients (95%). The most common chest radiographic interpretations were cardiac enlargement (27%), normal (24%), pleural effusion (23%), elevated hemidiaphragm (20%), pulmonary artery enlargement (19%), atelectasis (18%), and parenchymal pulmonary infiltrates (17%). The results of chest radiographs were abnormal for 509 of 655 patients (78%) who had undergone a major surgical procedure within 2 months of the diagnosis of pulmonary embolism: normal results for chest radiograph often accompanied pulmonary embolism after genitourinary procedures (37%), orthopedic surgery (29%), or gynecologic surgery (28%), whereas they rarely accompanied pulmonary emboli associated with thoracic procedures (4%). Chest radiographs were interpreted to show cardiac enlargement for 149 of 309 patients with right ventricular hypokinesis that was detected by echocardiography (sensitivity, 0.48) and for 178 of 485 patients without right ventricular hypokinesis (specificity, 0.63). Chest radiographs were interpreted to show pulmonary artery enlargement for 118 of 309 patients with right ventricular hypokinesis (sensitivity, 0.38) and for 117 of 483 patients without right ventricular hypokinesis (specificity, 0.76).
CONCLUSIONS: Cardiomegaly is the most common chest radiographic abnormality associated with acute pulmonary embolism. Neither pulmonary artery enlargement nor cardiomegaly appears sensitive or specific for the echocardiographic finding of right ventricular hypokinesis, an important predictor of mortality associated with acute pulmonary embolism.
M Miniati, R Prediletto, B Formichi, C Marini, G Di Ricco, L Tonelli, G Allescia, M Pistolesi
Accuracy of clinical assessment in the diagnosis of pulmonary embolism.
Am J Respir Crit Care Med. 1999 Mar;159(3):864-71. doi: 10.1164/ajrccm.159.3.9806130.
Abstract/Text
To provide clinical diagnostic criteria for pulmonary embolism (PE), we evaluated 750 consecutive patients with suspected PE who were enrolled in the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED). Prior to perfusion lung scanning, patients were examined independently by six pulmonologists according to a standardized diagnostic protocol. Study design required pulmonary angiography in all patients with abnormal scans. Patients are reported as two distinct groups: a first group of 500, whose data were analyzed to derive a clinical diagnostic algorithm for PE, and a second group of 250 in whom the diagnostic algorithm was validated. PE was diagnosed by angiography in 202 (40%) of the 500 patients in the first group. A diagnostic algorithm was developed that includes the identification of three symptoms (sudden onset dyspnea, chest pain, and fainting) and their association with one or more of the following abnormalities: electrocardiographic signs of right ventricular overload, radiographic signs of oligemia, amputation of hilar artery, and pulmonary consolidations compatible with infarction. The above three symptoms (singly or in some combination) were associated with at least one of the above electrocardiographic and radiographic abnormalities in 164 (81%) of 202 patients with confirmed PE and in only 22 (7%) of 298 patients without PE. The rate of correct clinical classification was 88% (440/500). In the validation group of 250 patients the prevalence of PE was 42% (104/250). In this group, the sensitivity and specificity of the clinical diagnostic algorithm for PE were 84% (95% CI: 77 to 91%) and 95% (95% CI: 91 to 99%), respectively. The rate of correct clinical classification was 90% (225/250). Combining clinical estimates of PE, derived from the diagnostic algorithm, with independent interpretation of perfusion lung scans helps restrict the need for angiography to a minority of patients with suspected PE.
PIOPED Investigators
Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED).
JAMA. 1990 May 23-30;263(20):2753-9.
Abstract/Text
To determine the sensitivities and specificities of ventilation/perfusion lung scans for acute pulmonary embolism, a random sample of 933 of 1493 patients was studied prospectively. Nine hundred thirty-one underwent scintigraphy and 755 underwent pulmonary angiography; 251 (33%) of 755 demonstrated pulmonary embolism. Almost all patients with pulmonary embolism had abnormal scans of high, intermediate, or low probability, but so did most without pulmonary embolism (sensitivity, 98%; specificity, 10%). Of 116 patients with high-probability scans and definitive angiograms, 102 (88%) had pulmonary embolism, but only a minority with pulmonary embolism had high-probability scans (sensitivity, 41%; specificity, 97%). Of 322 with intermediate-probability scans and definitive angiograms, 105 (33%) had pulmonary embolism. Follow-up and angiography together suggest pulmonary embolism occurred among 12% of patients with low-probability scans. Clinical assessment combined with the ventilation/perfusion scan established the diagnosis or exclusion of pulmonary embolism only for a minority of patients--those with clear and concordant clinical and ventilation/perfusion scan findings.
Nadine S Gibson, Maaike Sohne, Harry R Buller
Prognostic value of echocardiography and spiral computed tomography in patients with pulmonary embolism.
Curr Opin Pulm Med. 2005 Sep;11(5):380-4.
Abstract/Text
PURPOSE OF REVIEW: The identification of patients with pulmonary embolism who are at risk for mortality or severe morbidity in the early observation period is important because these patients may benefit from more aggressive initial treatment such as thrombolysis or catheter removal of the thrombus. Right ventricular dysfunction has been suggested to have a prognostic value for the occurrence of these adverse outcomes. The purpose of this review is to determine the prevalence and prognostic value of right ventricular dysfunction, in particular in normotensive patients with pulmonary embolism. The association between right ventricular dysfunction and outcome of pulmonary embolism was evaluated for studies using echocardiography, spiral computed tomography, or both to detect right ventricular dysfunction.
RECENT FINDINGS: Seven studies using echocardiography with a total of 3468 patients and six studies using spiral computed tomography with a total of 868 patients were identified. The prevalence of right ventricular dysfunction with echocardiography in normotensive patients was approximately 30 to 40%, with a positive predictive value for short-term mortality of approximately 5%. These indices could not be calculated for normotensive patients in the studies that used spiral computed tomography.
SUMMARY: The studies using echocardiography show that there is an association between right ventricular dysfunction and prognosis of pulmonary embolism in normotensive patients. Whether this is clinically useful in guiding more aggressive therapy remains to be determined, however. Thus far, the results of the studies with spiral computed tomography are too preliminary to enable definite conclusions to be drawn for the normotensive patient group.
Nils Kucher, Elisa Rossi, Marisa De Rosa, Samuel Z Goldhaber
Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm Hg or higher.
Arch Intern Med. 2005 Aug 8-22;165(15):1777-81. doi: 10.1001/archinte.165.15.1777.
Abstract/Text
BACKGROUND: The prognostic role of echocardiographic right ventricular (RV) dysfunction for predicting mortality in patients with acute pulmonary embolism and a preserved systemic arterial pressure remains controversial.
METHODS: We evaluated 1035 patients with pulmonary embolism from the International Cooperative Pulmonary Embolism Registry who (1) presented with systolic systemic arterial pressure of 90 mm Hg or higher and (2) who underwent echocardiography within 24 hours of a diagnosis of pulmonary embolism, showing presence (n = 405) or absence (n = 630) of RV hypokinesis. The main outcome measure was the cumulative survival rate through 30 days in patients with and without RV hypokinesis.
RESULTS: In patients with RV hypokinesis, the initial systolic systemic pressure was lower (125 +/- 22 mm Hg vs 131 +/- 22 mm Hg; P<.001), and the initial heart rate was higher (104 +/- 21 beats per minute vs 99 +/- 22 beats per minute; P<.001) than in patients without RV hypokinesis. Cancer was less often present (14.1% vs 22.5%, P = .001). The 30-day survival rates in patients with and without RV hypokinesis were 83.7% (95% confidence interval [CI], 79.3%-87.0%) and 90.6% (95% CI, 88.0%-92.6%), respectively (log-rank P value <.001). The univariate hazard ratio of RV hypokinesis for predicting 30-day mortality was 2.11 (95% CI, 1.41-3.16; P<.001). Right ventricular hypokinesis remained an independent predictor of 30-day mortality (hazard ratio, 1.94; 95% CI, 1.23-3.06) after adjusting for univariately significant predictors, including cancer, congestive heart failure, chronic lung disease, age older than 70 years, systolic arterial pressure of 100 mm Hg or lower, administration of thrombolytic therapy, and heart rate greater than 100 beats per minutes.
CONCLUSION: Among patients with pulmonary embolism who present with a systolic arterial pressure greater than or equal to 90 mm Hg, echocardiographic RV hypokinesis is an independent predictor of early death.
P C Come
Echocardiographic evaluation of pulmonary embolism and its response to therapeutic interventions.
Chest. 1992 Apr;101(4 Suppl):151S-162S.
Abstract/Text
Imaging and Doppler echocardiography permits assessment of right ventricular size and systolic function and of pulmonary arterial pressures, and it may facilitate detection of thromboemboli within the heart or pulmonary artery. In patients with acute pulmonary embolism of sufficient severity to appreciably increase right ventricular afterload, the right ventricle becomes dilated and hypokinetic. Tricuspid regurgitation is generally apparent, but in the absence of preexisting pulmonary arterial or left heart pathology, the regurgitant flow velocity suggests only mild to mild-moderate elevation of pulmonary arterial systolic pressure. The absence of a greater degree of pulmonary hypertension reflects the inability of the previously normal, nonhypertrophied right ventricle to generate a mean pulmonary arterial pressure in excess of about 40 mm Hg. The echocardiographic abnormalities resolve during recovery from pulmonary embolism. Currently being investigated is the question of whether right heart abnormalities resolve more rapidly with thrombolytic therapy than with heparin therapy alone.
M V McConnell, S D Solomon, M E Rayan, P C Come, S Z Goldhaber, R T Lee
Regional right ventricular dysfunction detected by echocardiography in acute pulmonary embolism.
Am J Cardiol. 1996 Aug 15;78(4):469-73.
Abstract/Text
This study analyzed the regional pattern of right ventricular (RV) dysfunction on transthoracic echocardiograms in patients with and without acute pulmonary embolism. Quantitative (centerline) and qualitative (wall motion score) analyses of segmental RV free wall motion were performed on a "training" cohort of 41 patients (group 1), including 14 patients with acute pulmonary embolism, 9 patients with primary pulmonary hypertension, and 18 normal subjects. Patients with acute pulmonary embolism had a distinct regional pattern of RV dysfunction, with akinesia of the mid-free wall (centerline excursion: -0.2 +/- 0.8 mm, p = 0.0001 vs normal) but normal motion at the apex (centerline excursion: 5.7 +/- 0.8 mm, p = NS vs normal). In contrast, patients with primary pulmonary hypertension had abnormal wall motion in all regions (p <0.03 vs normal). This echocardiographic finding of normal wall motion at the apex and abnormal wall motion in the mid-free wall in acute pulmonary embolism was then tested in a "validation" cohort of 85 patients (group 2), consisting of hospitalized patients with RV dysfunction from any cause, including 13 patients with acute pulmonary embolism. The finding had a 77% sensitivity and a 94% specificity for the diagnosis of acute pulmonary embolism, with a positive predictive value of 71% and a negative predictive value of 96%. Thus, a distinct echocardiographic pattern of regional RV dysfunction, in which the apex is spared occurs in acute pulmonary embolism. This finding should raise the level of clinical suspicion for the diagnosis of acute pulmonary embolism.
S Z Goldhaber, L Visani, M De Rosa
Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER)
Lancet. 1999 Apr 24;353(9162):1386-9.
Abstract/Text
BACKGROUND: Pulmonary embolism (PE) remains poorly understood. Rates of clinical outcomes such as death and recurrence vary widely among trials. We therefore established the International Cooperative Pulmonary Embolism Registry (ICOPER), with the aim of identifying factors associated with death.
METHODS: 2454 consecutive eligible patients with acute PE were registered from 52 hospitals in seven countries in Europe and North America. The primary outcome measure was all-cause mortality at 3 months. The prognostic effect of baseline factors on survival was assessed with multivariate analyses.
FINDINGS: 2110 (86.0%) patients had PE proven by necropsy, high-probability lung scan, pulmonary angiography, or venous ultrasonography plus high clinical suspicion; ICOPER accepted without independent review diagnoses and interpretation of imaging provided by participating centres; 3-month follow-up was completed in 98.0% of patients. The overall crude mortality rate at 3 months was 17.4% (426 of 2454 deaths, including 52 patients lost to follow-up): 179 of 397 (45.1%) deaths were ascribed to PE and 70 of 397 (17.6%) to cancer, and no information on the cause of death was available for 29 patients. After exclusion of 61 patients in whom PE was first discovered at necropsy, the mortality rate at 3 months was 15.3% (365 of 2393 deaths). On multiple-regression modelling, age over 70 years (hazard ratio 1.6 [95% CI 1.1-2.3]), cancer (2.3 [1.5-3.5]), congestive heart failure (2.4 [1.5-3.7]), chronic obstructive pulmonary disease (1.8 [1.2-2.7]), systolic arterial hypotension (2.9 [1.7-5.0]), tachypnoea (2.0 [1.2-3.2]), and right-ventricular hypokinesis on echocardiography (2.0 [1.3-2.9]) were identified as significant prognostic factors.
INTERPRETATION: PE remains an important clinical problem with a high mortality rate. Data from ICOPER provide rates and highlight adverse prognostic categories that will help in planning of future trials of high-risk PE patients.
J L Carson, M A Kelley, A Duff, J G Weg, W J Fulkerson, H I Palevsky, J S Schwartz, B T Thompson, J Popovich, T E Hobbins
The clinical course of pulmonary embolism.
N Engl J Med. 1992 May 7;326(19):1240-5. doi: 10.1056/NEJM199205073261902.
Abstract/Text
BACKGROUND: Pulmonary embolism is a potentially fatal disorder. Information about the outcome of clinically recognized pulmonary embolism is sparse, particularly given that new treatments for more seriously ill patients are now available.
METHODS: We prospectively followed 399 patients with pulmonary embolism diagnosed by lung scanning and pulmonary angiography, who were enrolled in a multicenter diagnostic trial. We reviewed all hospitalizations, all new investigations of pulmonary embolism, and all deaths among the patients within one year of diagnosis.
RESULTS: Of the 399 patients, 375 (94 percent) received treatment for pulmonary embolism, usually conventional anticoagulation. Only 10 patients (2.5 percent) died of pulmonary embolism; 9 of them had clinically suspected recurrent pulmonary embolism. Clinically apparent pulmonary embolism recurred in 33 patients (8.3 percent), of whom 45 percent died during follow-up. Ninety-five patients with pulmonary embolism (23.8 percent) died within one year. The conditions associated with these deaths were cancer (relative risk, 3.8; 95 percent confidence interval, 2.3 to 6.4), left-sided congestive heart failure (relative risk, 2.7; 95 percent confidence interval, 1.5 to 4.6), and chronic lung disease (relative risk, 2.2; 95 percent confidence interval, 1.2 to 4.0). The most frequent causes of death in patients with pulmonary embolism were cancer (in 34.7 percent), infection (22.1 percent), and cardiac disease (16.8 percent).
CONCLUSIONS: When properly diagnosed and treated, clinically apparent pulmonary embolism was an uncommon cause of death, and it recurred in only a small minority of patients. Most deaths were due to underlying diseases. Patients with pulmonary embolism who had cancer, congestive heart failure, or chronic lung disease had a higher risk of dying within one year than did other patients with pulmonary embolism.
Kenneth T Horlander, David M Mannino, Kenneth V Leeper
Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data.
Arch Intern Med. 2003 Jul 28;163(14):1711-7. doi: 10.1001/archinte.163.14.1711.
Abstract/Text
BACKGROUND: Pulmonary thromboembolism (PTE) is a common clinical problem that is associated with substantial morbidity and mortality. Estimates of PTE mortality and predictions of PTE trends have varied widely. These estimates play a role in the planning of national health strategies. The analysis of pulmonary embolism mortality trends and comorbidities may elucidate how well we treat and prevent the disease as well as identify additional risk factors.
METHODS: We analyzed PTE (International Classification of Diseases, Ninth Revision code 415.1) as reported on death certificates in the Multiple-Cause Mortality Files compiled by the National Center for Health Statistics from 1979 to 1998.
RESULTS: Of all the 42932973 decedents, 572773 (1.3%) had PTE listed on their death certificates and 194389 of these (33.9%) had PTE as the underlying cause of death. The age-adjusted rate of deaths with PTE decreased from 191 per million in 1979 to 94 per million in 1998 overall, decreasing 56% for men and 46% for women. During the study period, the age-adjusted mortality rates for blacks were consistently 50% higher than those for whites, and those for whites were 50% higher than those for people of other races (Asian, American Indian, etc). Within racial strata, mortality rates were consistently 20% to 30% higher among men than among women. Conditions that were of higher likelihood in persons who died with PTE included thrombophlebitis, fractures, trauma, postoperative complications, certain cancers, and the inflammatory bowel diseases.
CONCLUSIONS: Mortality with PTE in the United States has decreased during the 20-year period. The mortality rates between men and women and between racial groups vary substantially. These findings may be useful in better directing preventive therapy efforts.
Mathilde Nijkeuter, Maaike Söhne, Lidwine W Tick, Pieter Willem Kamphuisen, Mark H H Kramer, Laurens Laterveer, Anja A van Houten, Marieke J H A Kruip, Frank W G Leebeek, Harry R Büller, Menno V Huisman, Christopher Study Investigators
The natural course of hemodynamically stable pulmonary embolism: Clinical outcome and risk factors in a large prospective cohort study.
Chest. 2007 Feb;131(2):517-23. doi: 10.1378/chest.05-2799.
Abstract/Text
BACKGROUND: Pulmonary embolism (PE) is a potentially fatal disease with risks of recurrent venous thrombotic events (venous thromboembolism [VTE]) and major bleeding from anticoagulant therapy. Identifying risk factors for recurrent VTE, bleeding, and mortality may guide clinical decision making.
OBJECTIVE: To evaluate the incidence of recurrent VTE, hemorrhagic complications, and mortality in patients with PE, and to identify risk factors and the time course of these events.
DESIGN: We evaluated consecutive patients with PE derived from a prospective management study, who were followed for 3 months, treated with anticoagulants, and underwent objective diagnostic testing for suspected recurrent VTE or bleeding.
RESULTS: Of 673 patients with complete follow-up, 20 patients (3.0%; 95% confidence interval [CI], 1.8 to 4.6%) had recurrent VTE. Eleven of 14 patients with recurrent PE had a fatal PE (79%; 95% CI, 49 to 95%), occurring mostly in the first week after diagnosis of initial PE. In 23 patients (3.4%; 95% CI, 2.2 to 5.1%), a hemorrhagic complication occurred, 10 of which were major bleeds (1.5%; 95% CI, 0.7 to 2.7%), and 2 were fatal (0.3%; 95% CI, 0.04 to 1.1%). During the 3-month follow-up, 55 patients died (8.2%; 95% CI, 6.2 to 10.5%). Risk factors for recurrent VTE were immobilization for > 3 days and being an inpatient; having COPD or malignancies were risk factors for bleeding. Higher age, immobilization, malignancy, and being an inpatient were risk factors for mortality.
CONCLUSIONS: Recurrent VTE occurred in a small percentage of patients treated for an acute PE, and the majority of recurrent PEs were fatal. Immobilization, hospitalization, age, COPD, and malignancies were risk factors for recurrent VTE, bleeding, and mortality. Close monitoring may be indicated in these patients, precluding them from out-of-hospital start of treatment.
W W COON, P W WILLIS
Deep venous thrombosis and pulmonary embolism: prediction, prevention and treatment.
Am J Cardiol. 1959 Nov;4:611-21.
Abstract/Text
L A Soloff, T Rodman
Acute pulmonary embolism. II. Clinical.
Am Heart J. 1967 Dec;74(6):829-47.
Abstract/Text
Silvy Laporte, Patrick Mismetti, Hervé Décousus, Fernando Uresandi, Remedios Otero, Jose Luis Lobo, Manuel Monreal, RIETE Investigators
Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry.
Circulation. 2008 Apr 1;117(13):1711-6. doi: 10.1161/CIRCULATIONAHA.107.726232. Epub 2008 Mar 17.
Abstract/Text
BACKGROUND: Clinical predictors for fatal pulmonary embolism (PE) in patients with venous thromboembolism have never been studied.
METHODS AND RESULTS: Using data from the international prospective Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry about patients with objectively confirmed symptomatic acute venous thromboembolism, we determined independent predictive factors for fatal PE. Between March 2001 and July 2006, 15 520 consecutive patients (mean age+/-SD, 66.3+/-16.9 years; 49.7% men) with acute venous thromboembolism were included. Symptomatic deep-vein thrombosis without symptomatic PE was observed in 58.0% (n=9008) of patients, symptomatic nonmassive PE in 40.4% (n=6264), and symptomatic massive PE in 1.6% (n=248). At 3 months, the cumulative rates of overall mortality and fatal PE were 8.65% and 1.68%, respectively. On multivariable analysis, patients with symptomatic nonmassive PE at presentation exhibited a 5.42-fold higher risk of fatal PE compared with patients with deep-vein thrombosis without symptomatic PE (P<0.001). The risk of fatal PE was multiplied by 17.5 in patients presenting with a symptomatic massive PE. Other clinical factors independently associated with an increased risk of fatal PE were immobilization for neurological disease, age >75 years, and cancer.
CONCLUSIONS: PE remains a potentially fatal disease. The clinical predictors identified in the present study should be included in any clinical risk stratification scheme to optimally adapt the treatment of PE to the risk of the fatal outcome.
Drahomir Aujesky, D Scott Obrosky, Roslyn A Stone, Thomas E Auble, Arnaud Perrier, Jacques Cornuz, Pierre-Marie Roy, Michael J Fine
A prediction rule to identify low-risk patients with pulmonary embolism.
Arch Intern Med. 2006 Jan 23;166(2):169-75. doi: 10.1001/archinte.166.2.169.
Abstract/Text
BACKGROUND: A simple prognostic model could help identify patients with pulmonary embolism who are at low risk of death and are candidates for outpatient treatment.
METHODS: We randomly allocated 15,531 retrospectively identified inpatients who had a discharge diagnosis of pulmonary embolism from 186 Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples. We derived our rule to predict 30-day mortality using classification tree analysis and patient data routinely available at initial examination as potential predictor variables. We used data from a European prospective study to externally validate the rule among 221 inpatients with pulmonary embolism. We determined mortality and nonfatal adverse medical outcomes across derivation and validation samples.
RESULTS: Our final model consisted of 10 patient factors (age > or = 70 years; history of cancer, heart failure, chronic lung disease, chronic renal disease, and cerebrovascular disease; and clinical variables of pulse rate > or = 110 beats/min, systolic blood pressure < 100 mm Hg, altered mental status, and arterial oxygen saturation < 90%). Patients with none of these factors were defined as low risk. The 30-day mortality rates for low-risk patients were 0.6%, 1.5%, and 0% in the derivation, internal validation, and external validation samples, respectively. The rates of nonfatal adverse medical outcomes were less than 1% among low-risk patients across all study samples.
CONCLUSIONS: This simple prediction rule accurately identifies patients with pulmonary embolism who are at low risk of short-term mortality and other adverse medical outcomes. Prospective validation of this rule is important before its implementation as a decision aid for outpatient treatment.
Paul L den Exter, Josien van Es, Frederikus A Klok, Lucia J Kroft, Marieke J H A Kruip, Pieter Willem Kamphuisen, Harry R Büller, Menno V Huisman
Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism.
Blood. 2013 Aug 15;122(7):1144-9; quiz 1329. doi: 10.1182/blood-2013-04-497545. Epub 2013 Jun 4.
Abstract/Text
The clinical significance of subsegmental pulmonary embolism (SSPE) remains to be determined. This study aimed to investigate whether SSPE forms a distinct subset of thromboembolic disease compared with more proximally located pulmonary embolism (PE). We analyzed 3728 consecutive patients with clinically suspected PE. SSPE patients were contrasted to patients with more proximal PE and to patients in whom suspected PE was ruled out, in regards of the prevalence of thromboembolic risk factors and the 3-month risks of recurrent venous thromboembolism (VTE) and mortality. PE was confirmed in 748 patients, of whom 116 (16%) had SSPE; PE was ruled out in 2980 patients. No differences were seen in the prevalence of VTE risk factors, the 3-month risk of recurrent VTE (3.6% vs 2.5%; P = .42), and mortality (10.7% vs 6.5%; P = .17) between patients with SSPE and those with more proximal PE. When compared with patients without PE, aged >60 years, recent surgery, estrogen use, and male gender were found to be independent predictors for SSPE, and patients with SSPE were at an increased risk of VTE during follow-up (hazard ratio: 3.8; 95% CI: 1.3-11.1). This study indicates that patients with SSPE mimic those with more proximally located PE in regards to their risk profile and clinical outcome.
Paul D Stein, Abdo Y Yaekoub, Fadi Matta, Muhammad Janjua, Rushi M Patel, Lawrence R Goodman, Martin L Gross, James E Denier
Resolution of pulmonary embolism on CT pulmonary angiography.
AJR Am J Roentgenol. 2010 May;194(5):1263-8. doi: 10.2214/AJR.09.3410.
Abstract/Text
OBJECTIVE: The objective of our study was to retrospectively determine the rate of resolution of pulmonary emboli (PEs) in individual vessels and the rate of complete resolution of PEs on CT angiography.
MATERIALS AND METHODS: Follow-up CT pulmonary angiograms, obtained during the period from January 2006 through May 2009, of 69 patients with acute PE from two hospitals were assessed. Initial and follow-up CT angiograms were reread together by one radiologist at both of the hospitals. Images were obtained using a 10-, 16-, 40-, or 64-MDCT angiography unit with a 0.5-mm collimation, 1.25- to 2.0-mm reconstruction, 0.3- to 0.5-second rotation time, and 7.5-mm/rotation table speed. All CT angiograms were obtained using a PE protocol.
RESULTS: Follow-up CT angiograms were obtained in 35 men and 34 women who ranged in age from 17 to 92 years (mean age, 58 +/- 17 [SD] years). Complete CT angiographic resolution of PE was seen in six of 15 patients (40%) 2-7 days after diagnostic imaging. After day 28, complete resolution occurred in 17 of 21 patients (81%). The main pulmonary arteries showed complete PE resolution during days 2-7 in seven of nine patients (78%) and after day 28 in 34 of 36 (94%). The lobar pulmonary arteries showed complete resolution of PE during days 2-7 in 23 of 33 patients (70%) and after 28 days in 44 of 48 (92%). The segmental pulmonary arteries showed complete resolution during days 2-7 in eight of 21 patients (38%) and after day 28 in 38 of 38 (100%).
CONCLUSION: Most patients (81%) showed complete resolution of PE on CT angiography after 28 days. PEs resolved faster in the main and lobar pulmonary arteries than in the segmental branches.
Ayaz Aghayev, Alessandro Furlan, Amol Patil, Serter Gumus, Kyung Nyeo Jeon, Bumwoo Park, Kyongtae T Bae
The rate of resolution of clot burden measured by pulmonary CT angiography in patients with acute pulmonary embolism.
AJR Am J Roentgenol. 2013 Apr;200(4):791-7. doi: 10.2214/AJR.12.8624.
Abstract/Text
OBJECTIVE: The purpose of this article is to quantitatively assess the rate of resolution of clot burden detected on pulmonary CT angiography (CTA) in patients with acute pulmonary embolism (PE).
MATERIALS AND METHODS: We evaluated 111 consecutive patients (55 men and 56 women) in a retrospective cohort who were diagnosed with PE by pulmonary CTA and had at least one follow-up pulmonary CTA within 1 year. Two radiologists in consensus measured the volume of each clot using a semiautomated quantification program. Semiquantitative measures of clot burden were also computed. The resolution rates of the total clot volume, as well as clot volumes of the central (main and lobar) and peripheral vessels (segmental and subsegmental), were analyzed.
RESULTS: The mean (± SD) clot volume per study was 3403.3 ± 6505.6 mm(3) at baseline and 531.6 ± 2383.5 mm(3) at the follow-up pulmonary CTA. Overall, 85 patients (77% ) showed complete resolution at the follow-up pulmonary CTA. Complete resolution was seen in 17 of 30 patients (56.7%) at a follow-up interval of 1-14 days, in 24 of 31 patients (77.4%) at 29-90 days, and in 32 of 34 patients (94.1%) after 90 days. The total clot volume measurements summed for all patients decreased by 78% (central clot, 69.4%; peripheral clot, 86.0%) at 14 days, by 96.6% (central clot, 93.4%; peripheral clot, 100%) at 90 days, and by 97.7% (central clot, 95.9%; peripheral clot, 100%) after 90 days.
CONCLUSION: Clot burden resolved completely in 77% of patients during the follow-up period. Our analysis showed that clots resolved faster in the peripheral arteries than in the central pulmonary arteries.
Yugo Yamashita, Takeshi Morimoto, Hidewo Amano, Toru Takase, Seiichi Hiramori, Kitae Kim, Maki Oi, Masaharu Akao, Yohei Kobayashi, Mamoru Toyofuku, Toshiaki Izumi, Tomohisa Tada, Po-Min Chen, Koichiro Murata, Yoshiaki Tsuyuki, Syunsuke Saga, Tomoki Sasa, Jiro Sakamoto, Minako Kinoshita, Kiyonori Togi, Hiroshi Mabuchi, Kensuke Takabayashi, Hiroki Shiomi, Takao Kato, Takeru Makiyama, Koh Ono, Takeshi Kimura
Validation of simplified PESI score for identification of low-risk patients with pulmonary embolism: From the COMMAND VTE Registry.
Eur Heart J Acute Cardiovasc Care. 2020 Jun;9(4):262-270. doi: 10.1177/2048872618799993. Epub 2018 Sep 11.
Abstract/Text
BACKGROUND: The simplified pulmonary embolism severity index (sPESI) score has been reported to be useful in predicting 30-day mortality for patients with pulmonary embolism, which helps the identification of low-risk patients for early hospital discharge or home treatment. However, therapeutic decision-making should also be based on the risks of adverse events other than mortality.
METHODS: The COMMAND VTE Registry is a multicentre registry enrolling consecutive patients with acute symptomatic venous thromboembolism in Japan between January 2010 and August 2014, and the current study population consisted of 1715 patients with pulmonary embolism. We calculated the sPESI score for each patient, and compared 30-day rates of mortality, recurrent venous thromboembolism and major bleeding between sPESI scores of 0 and 1 or greater.
RESULTS: Patients with a sPESI score of 0 accounted for 383 (22%) patients, and 110 (6.4%) patients died within 30 days. The cumulative 30-day incidence of mortality was lower in patients with a sPESI score of 0 than those with a sPESI score of 1 or greater (0.5% vs. 8.1%, log rank P<0.001). There was no significant difference in the cumulative 30-day incidence of recurrent venous thromboembolism between patients with a sPESI score of 0 and 1 or greater (1.3% vs. 2.8%, log rank P=0.11). The cumulative 30-day incidence of major bleeding was lower in patients with a sPESI score of 0 than those with a sPESI score of 1 or greater (1.1% vs. 4.0%, log rank P=0.005).
CONCLUSIONS: In patients with a sPESI score of 0, the 30-day mortality, recurrent venous thromboembolism and major bleeding rates were reasonably low. The sPESI score could be useful to identify candidates for early hospital discharge or home treatment.
Ryuki Chatani, Yugo Yamashita, Takeshi Morimoto, Nao Muraoka, Wataru Shioyama, Tatsuhiro Shibata, Yuji Nishimoto, Yoshito Ogihara, Kosuke Doi, Maki Oi, Taro Shiga, Daisuke Sueta, Kitae Kim, Yasuhiro Tanabe, Norimichi Koitabashi, Takuma Takada, Satoshi Ikeda, Hitoshi Nakagawa, Takayuki Mitsuhashi, Masaaki Shoji, Jiro Sakamoto, Shinji Hisatake, Yutaka Ogino, Masashi Fujita, Naohiko Nakanishi, Tomohiro Dohke, Seiichi Hiramori, Ryuzo Nawada, Kazuhisa Kaneda, Kazunori Mushiake, Hiromi Yamamoto, Kazushige Kadota, Koh Ono, Takeshi Kimura, ONCO PE Trial Investigators
Home Treatment for Active Cancer Patients With Low-Risk Pulmonary Embolism - A Predetermined Companion Report From the ONCO PE Trial.
Circ J. 2024 Mar 8;. doi: 10.1253/circj.CJ-24-0004. Epub 2024 Mar 8.
Abstract/Text
BACKGROUND: Patients with appropriately selected low-risk pulmonary embolism (PE) can be treated at home, although it has been controversial whether applies to patients with cancer, who are considered not to be at low risk.Methods and Results: The current predetermined companion report from the ONCO PE trial evaluated the 3-month clinical outcomes of patients with home treatment and those with in-hospital treatment. The ONCO PE trial was a multicenter, randomized clinical trial among 32 institutions in Japan investigating the optimal duration of rivaroxaban treatment in cancer-associated PE patients with a score of 1 using the simplified version of the Pulmonary Embolism Severity Index (sPESI). Among 178 study patients, there were 66 (37%) in the home treatment group and 112 (63%) in the in-hospital treatment group. The primary endpoint of a composite of PE-related death, recurrent venous thromboembolism (VTE) and major bleeding occurred in 3 patients (4.6% [0.0-9.6%]) in the home treatment group and in 2 patients (1.8% [0.0-4.3%]) in the in-hospital treatment group. In the home treatment group, there were no cases of PE-related death or recurrent VTE, but major bleeding occurred in 3 patients (4.6% [0.0-9.6%]), and 2 patients (3.0% [0.0-7.2%]) required hospitalization due to bleeding events.
CONCLUSIONS: Active cancer patients with PE of sPESI score=1 could be potential candidates for home treatment.
[www.j-circ.or.jp/guideline/pdf/JCS2017_ito_h.pdf 日本循環器学会編：肺血栓塞栓症および深部静脈血栓症の診断、治療、予防に関するガイドライン（2017年改訂版）、班長：伊藤正明、2017年].
D W BARRITT, S C JORDAN
Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial.
Lancet. 1960 Jun 18;1(7138):1309-12.
Abstract/Text
R D Hull, G E Raskob, J Hirsh, R M Jay, J R Leclerc, W H Geerts, D Rosenbloom, D L Sackett, C Anderson, L Harrison
Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis.
N Engl J Med. 1986 Oct 30;315(18):1109-14. doi: 10.1056/NEJM198610303151801.
Abstract/Text
We performed a randomized double-blind trial comparing continuous intravenous heparin with intermittent subcutaneous heparin in the initial treatment of 115 patients with acute proximal deep-vein thrombosis. Intermittent subcutaneous heparin as administered in this trial was inferior to continuous intravenous heparin in preventing recurrent venous thromboembolism. The subcutaneous heparin regimen induced an initial anticoagulant response below the target therapeutic range in the majority of patients and resulted in a high frequency of recurrent venous thromboembolism (11 of 57 patients, 19.3 percent), which was virtually confined to patients with a subtherapeutic anticoagulant response. In contrast, continuous intravenous heparin induced a therapeutic anticoagulant response in the majority of patients and a low frequency of recurrent events (3 of 58 patients, 5.2 percent; P = 0.024); the recurrences were limited to patients with an initial subtherapeutic anticoagulant response. The results of this trial establish the efficacy of intravenous heparin in the treatment of proximal venous thrombosis and suggest a relation between the effectiveness of heparin and the levels of anticoagulation achieved; such a relation could explain the observed failure of the subcutaneous regimen.
S Schulman, S Granqvist, M Holmström, A Carlsson, P Lindmarker, P Nicol, S G Eklund, S Nordlander, G Lärfars, B Leijd, O Linder, E Loogna
The duration of oral anticoagulant therapy after a second episode of venous thromboembolism. The Duration of Anticoagulation Trial Study Group.
N Engl J Med. 1997 Feb 6;336(6):393-8. doi: 10.1056/NEJM199702063360601.
Abstract/Text
BACKGROUND: A consensus has not been reached about the optimal duration of oral anticoagulant therapy after a second episode of venous thromboembolism.
METHODS: In a multicenter trial, we compared six months of oral anticoagulant therapy with anticoagulant therapy continued indefinitely in patients who had had a second episode of venous thromboembolism. Of 227 patients enrolled, 111 were randomly assigned to six months of anticoagulation and 116 were assigned to receive anticoagulant therapy indefinitely; for both groups, the target international normalized ratio was 2.0 to 2.85. The initial episodes of deep-vein thrombosis (n = 193) and pulmonary embolism (n = 34), as well as recurrent episodes, were all objectively confirmed.
RESULTS: After four years of follow-up, there were 26 recurrences of venous thromboembolism that fulfilled the diagnostic criteria, 23 in the group assigned to six months of therapy (20.7 percent) and 3 in the group assigned to continuing therapy (2.6 percent). The relative risk of recurrence in the group assigned to six months of therapy, as compared with the group assigned to therapy of indefinite duration, was 8.0 (95 percent confidence interval, 2.5 to 25.9). There were 13 major hemorrhages, 3 in the six-month group, (2.7 percent) and 10 in the infinite-treatment group (8.6 percent). The relative risk of major hemorrhage in the six-month group, as compared with the infinite-treatment group was 0.3 (95 percent confidence interval, 0.1 to 1.1). There was no difference in mortality between the two groups.
CONCLUSIONS: Prophylactic oral anticoagulation that was continued for an indefinite period after a second episode of venous thromboembolism was associated with a much lower rate of recurrence during four years of follow-up than treatment for six months. However, there was a trend toward a higher risk of major hemorrhage when anticoagulation was continued indefinitely.
P Prandoni, A W Lensing, H R Büller, A Cogo, M H Prins, A M Cattelan, S Cuppini, F Noventa, J W ten Cate
Deep-vein thrombosis and the incidence of subsequent symptomatic cancer.
N Engl J Med. 1992 Oct 15;327(16):1128-33. doi: 10.1056/NEJM199210153271604.
Abstract/Text
BACKGROUND: In contrast to the established relation between overt cancer and subsequent venous thromboembolism, it is unclear whether symptomatic deep-vein thrombosis is associated with a risk of subsequent overt malignant disease.
METHODS: Two hundred sixty consecutive patients with symptomatic, venographically proved deep-vein thrombosis were enrolled in a study, of whom 250 were followed during a two-year period. Among those assessed during follow-up, the incidence of subsequently detected cancer in the 105 patients with secondary venous thrombosis (i.e., thrombosis associated with a well-recognized risk factor other than cancer) was compared with the incidence of cancer in the 145 patients with idiopathic venous thrombosis.
RESULTS: Routine examination at the time of diagnosis of the venous thrombosis revealed cancer in 5 of the 153 enrolled patients with idiopathic venous thrombosis (3.3 percent) and in none of the 107 enrolled patients with secondary venous thrombosis. During follow-up, overt cancer developed in 2 of the 105 patients with secondary venous thrombosis (1.9 percent) and in 11 of the 145 patients with idiopathic venous thrombosis (7.6 percent; odds ratio, 2.3; 95 percent confidence interval, 1.0 to 5.2; P = 0.043). Of the 145 patients with idiopathic venous thrombosis, 35 had confirmed recurrent thromboembolism. Overt cancer subsequently developed in 6 of the 35 (17.1 percent). The incidence of cancer in the patients with recurrent idiopathic venous thrombosis was higher than that in the patients with secondary venous thrombosis (P = 0.008; odds ratio, 9.8; 95 percent confidence interval, 1.8 to 52.2) or in the patients with idiopathic venous thrombosis that did not recur (P = 0.024; odds ratio, 4.3; 95 percent confidence interval, 1.2 to 15.3).
CONCLUSIONS: There is a statistically significant and clinically important association between idiopathic venous thrombosis and the subsequent development of clinically overt cancer, especially among patients in whom venous thromboembolism recurs during follow-up.
M N Levine, J Hirsh, M Gent, A G Turpie, J Weitz, J Ginsberg, W Geerts, J LeClerc, J Neemeh, P Powers
Optimal duration of oral anticoagulant therapy: a randomized trial comparing four weeks with three months of warfarin in patients with proximal deep vein thrombosis.
Thromb Haemost. 1995 Aug;74(2):606-11.
Abstract/Text
The optimal duration of oral anticoagulant therapy for patients with acute proximal deep vein thrombosis (DVT) is uncertain. Based on the hypothesis that a normal impedance plethysmogram (IPG) following DVT defines a group of patients at low risk of recurrent venous thromboembolism (VTE), a trial was conducted to evaluate the efficacy of only four weeks of warfarin. Patients with venographically confirmed acute proximal DVT who had received four weeks of warfarin after initial heparin and whose four week IPG was normal were allocated to either continue warfarin (targeted International Normalized Ratio 2.0 to 3.0) for a further eight weeks or receive placebo. Patients with an abnormal four week IPG received warfarin for a further eight weeks. Based on clinical characteristics at the time of the qualifying thrombosis, all patients were classified as having either continuing or transient risk factors for recurrent VTE. During the eight weeks following randomization, nine (8.6%) of the 105 placebo patients developed recurrent VTE compared to one (0.9%) of the 109 warfarin patients, P = 0.009. Over the entire 11 months of follow-up, 12 placebo patients developed recurrence compared to seven warfarin patients, P = 0.3. Nineteen of the 192 patients with an abnormal four week IPG experienced recurrence during the nine months after discontinuing warfarin. In the 301 patients who received three months of warfarin in the randomized trial or in the cohort study, all 26 recurrent events were in the 212 patients with continuing risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Hokusai-VTE Investigators, Harry R Büller, Hervé Décousus, Michael A Grosso, Michele Mercuri, Saskia Middeldorp, Martin H Prins, Gary E Raskob, Sebastian M Schellong, Lee Schwocho, Annelise Segers, Minggao Shi, Peter Verhamme, Phil Wells
Edoxaban versus warfarin for the treatment of symptomatic venous thromboembolism.
N Engl J Med. 2013 Oct 10;369(15):1406-15. doi: 10.1056/NEJMoa1306638. Epub 2013 Aug 31.
Abstract/Text
BACKGROUND: Whether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear.
METHODS: In a randomized, double-blind, noninferiority study, we randomly assigned patients with acute venous thromboembolism, who had initially received heparin, to receive edoxaban at a dose of 60 mg once daily, or 30 mg once daily (e.g., in the case of patients with creatinine clearance of 30 to 50 ml per minute or a body weight below 60 kg), or to receive warfarin. Patients received the study drug for 3 to 12 months. The primary efficacy outcome was recurrent symptomatic venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding.
RESULTS: A total of 4921 patients presented with deep-vein thrombosis, and 3319 with a pulmonary embolism. Among patients receiving warfarin, the time in the therapeutic range was 63.5%. Edoxaban was noninferior to warfarin with respect to the primary efficacy outcome, which occurred in 130 patients in the edoxaban group (3.2%) and 146 patients in the warfarin group (3.5%) (hazard ratio, 0.89; 95% confidence interval [CI], 0.70 to 1.13; P<0.001 for noninferiority). The safety outcome occurred in 349 patients (8.5%) in the edoxaban group and 423 patients (10.3%) in the warfarin group (hazard ratio, 0.81; 95% CI, 0.71 to 0.94; P=0.004 for superiority). The rates of other adverse events were similar in the two groups. A total of 938 patients with pulmonary embolism had right ventricular dysfunction, as assessed by measurement of N-terminal pro-brain natriuretic peptide levels; the rate of recurrent venous thromboembolism in this subgroup was 3.3% in the edoxaban group and 6.2% in the warfarin group (hazard ratio, 0.52; 95% CI, 0.28 to 0.98).
CONCLUSIONS: Edoxaban administered once daily after initial treatment with heparin was noninferior to high-quality standard therapy and caused significantly less bleeding in a broad spectrum of patients with venous thromboembolism, including those with severe pulmonary embolism. (Funded by Daiichi-Sankyo; Hokusai-VTE ClinicalTrials.gov number, NCT00986154.).
C Jerjes-Sanchez, A Ramírez-Rivera, de Lourdes García M, R Arriaga-Nava, S Valencia, A Rosado-Buzzo, JA Pierzo, E Rosas
Streptokinase and Heparin versus Heparin Alone in Massive Pulmonary Embolism: A Randomized Controlled Trial.
J Thromb Thrombolysis. 1995;2(3):227-229.
Abstract/Text
To test the efficacy of thrombolytic therapy in massive pulmonary embolism, we conducted a prospective randomized controlled trial. Eight patients were randomized to receive either 1,500,000 IU of streptokinase in 1 hour through a peripheral vein followed by heparin or heparin alone. All patients had major risk factors for deep vein thrombosis (DVT) and were considered to have high clinical suspicion for pulmonary embolism (PE). At baseline all patients had a similar degree of systemic arterial hypotension, pulmonary arterial hypertension, and right ventricular dysfunction. The time of onset of cardiogenic shock in both groups was comparable (2.25 +/- 0.5 hours in the streptokinase group and 1.75 +/- 0.96 hours in the heparin group). The four patients who were randomized to streptokinase improved in the first hour after treatment, survived, and in 2 years of follow-up are without pulmonary arterial hypertension. All four patients treated with heparin alone died from 1 to 3 hours after arrival at the emergency room (p = 0.02). Post-thrombolytic therapy the diagnosis of PE was sustained in the streptokinase group by high probability V/Q lung scans and proven DVT. A necropsy study performed in three patients in the heparin group showed massive pulmonary embolism and right ventricular myocardial infarction, without significant coronary arterial obstruction. The results indicate that thrombolytic therapy reduces the mortality rate of massive acute pulmonary embolism.
B Ly, H Arnesen, H Eie, R Hol
A controlled clinical trial of streptokinase and heparin in the treatment of major pulmonary embolism.
Acta Med Scand. 1978;203(6):465-70.
Abstract/Text
Treatment with streptokinase or heparin was allocated randomly to 20 patients with major pulmonary embolism verified by angiography. In addition, 4 patients treated with streptokinase and 1 patient treated with heparin were included in the trial prior to the start of treatment. Streptokinase of heparin was given for 72 hours and pulmonary angiography was repeated. The angiographic evidence of thrombolysis was significantly greater (p less than 0.01) in the 14 patients treated with streptokinase than in the 11 treated with heparin. In the heparin group, 1 patient died from massive embolism 15 hours after the start of treatment. In another patient who died 4 weeks later from cerebral glibolastoma, persistent massive embolism contributed to the fatal outcome. In the streptokinase group, 1 patient with a metastatic pulmonary carcinoma died 3 weeks after the start of treatment from gangrene of both legs following thrombotic occlusion of the inferior vena cava. Bleeding was more common after treatment with streptokinase than with heparin, but was not a serious problem in any patient. It is concluded that patients with life-threatening pulmonary embolism should be offered the benefits of streptokinase.
Urokinase pulmonary embolism trial. Phase 1 results: a cooperative study.
JAMA. 1970 Dec 21;214(12):2163-72.
Abstract/Text
Clive Kearon, Elie A Akl, Anthony J Comerota, Paolo Prandoni, Henri Bounameaux, Samuel Z Goldhaber, Michael E Nelson, Philip S Wells, Michael K Gould, Francesco Dentali, Mark Crowther, Susan R Kahn, American College of Chest Physicians
Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.
Chest. 2012 Feb;141(2 Suppl):e419S-94S. doi: 10.1378/chest.11-2301.
Abstract/Text
BACKGROUND: This article addresses the treatment of VTE disease.
METHODS: We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence.
RESULTS: For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C).
CONCLUSION: Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences.
Lishan Aklog, Christopher S Williams, John G Byrne, Samuel Z Goldhaber
Acute pulmonary embolectomy: a contemporary approach.
Circulation. 2002 Mar 26;105(12):1416-9.
Abstract/Text
BACKGROUND: Acute pulmonary embolism confers a high mortality rate despite advances in diagnosis and therapy. Thrombolysis is often effective but has a high frequency of major bleeding complications, especially intracranial hemorrhage. Therefore, we liberalized our criteria for acute pulmonary embolectomy and considered operating on patients with anatomically extensive pulmonary embolism and concomitant moderate to severe right ventricular dysfunction despite preserved systemic arterial pressure.
METHODS AND RESULTS: We report 29 (17 men and 12 women) consecutive patients who underwent embolectomy from October 1999 through October 2001. Twenty-six patients (89%) survived surgery and were alive more than 1 month postoperatively. Median follow-up is 10 months.
CONCLUSION: The high survival rate of 89% can be attributed to improved surgical technique, rapid diagnosis and triage, and careful patient selection. We hope that other tertiary centers will evaluate pulmonary embolism patients with an algorithm that includes surgical embolectomy as one of several therapeutic options. Our contemporary approach to pulmonary embolectomy no longer confines this operation to a treatment of last resort reserved for clinically desperate circumstances.
Paul D Stein, Majd Alnas, Afzal Beemath, Nikunj R Patel
Outcome of pulmonary embolectomy.
Am J Cardiol. 2007 Feb 1;99(3):421-3. doi: 10.1016/j.amjcard.2006.08.050. Epub 2006 Dec 15.
Abstract/Text
In view of the importance of pulmonary embolectomy as a possible treatment option in highly compromised patients with acute pulmonary embolism, a systematic review of immediate surgical outcomes was performed. Pooled data from 46 reported case series of patients operated from 1961 to 2006 showed an average mortality of 389 of 1,300 patients (30%). In patients operated on before 1985, the average mortality was 32%, compared with 20% in patients operated from 1985 to 2005. In patients who experienced cardiac arrest before pulmonary embolectomy, the operative mortality was 59% compared with 29% in patients who did not have preoperative cardiac arrest. In conclusion, despite generally high mortality in patients who undergo pulmonary embolectomy, it may have life-saving potential in some instances.
Zachary J Osborne, Peter Rossi, John Aucar, Sadru Dharamsy, Scott Cook, Brian Wheatley
Surgical pulmonary embolectomy in a community hospital.
Am J Surg. 2014 Mar;207(3):337-41; discussion 340-1. doi: 10.1016/j.amjsurg.2013.10.011. Epub 2013 Dec 8.
Abstract/Text
BACKGROUND: Surgical pulmonary embolectomy (SPE) is indicated for a pulmonary embolism associated with hemodynamic instability. A review of the literature demonstrates that most studies of SPE are conducted at large academic medical centers. This series is from a 325-bed community hospital.
METHODS: A retrospective chart review was performed of patients undergoing SPE from January 2008 to December 2012. All patients aged >18 years were reviewed for 30-day mortality, length of hospital stay, comorbidities, and preoperative hemodynamic parameters.
RESULTS: Fifteen patients (7 men and 8 women; median age, 55.5 years; range, 20-72 years) underwent SPE. There were 2 deaths (13.3%). Four of the patients underwent catheter-directed interventions before SPE. The mean length of hospital stay was 12 days.
CONCLUSIONS: These data suggest that SPE is associated with favorable outcomes in the appropriate community setting, and the mortality rate seen in this study compares favorably with the nationwide average of 27.2%.
Copyright © 2014 Elsevier Inc. All rights reserved.
Paul D Stein, Fadi Matta
Pulmonary embolectomy in elderly patients.
Am J Med. 2014 Apr;127(4):348-50. doi: 10.1016/j.amjmed.2013.11.011. Epub 2013 Dec 11.
Abstract/Text
OBJECTIVE: The relation of age to case fatality rate in patients undergoing pulmonary embolectomy has not been reported. In view of the importance of age in the selection of patients who may be candidates for pulmonary embolectomy, we explored the database of the Nationwide Inpatient Sample to determine the impact of age on the case fatality rate.
METHODS: Patients with pulmonary embolism who underwent pulmonary embolectomy in short-stay hospitals throughout the United States, 1999-2008, were identified from the Nationwide Inpatient Sample. In-hospital all-cause case fatality rate was assessed according to age.
RESULTS: The proportion of patients who underwent pulmonary embolectomy decreased with age among both stable and unstable patients. Case fatality rate with pulmonary embolectomy in stable patients increased with age beginning at age 51 to 60 years. Among patients aged 51 to 60 years, the case fatality rate was 100 of 575 (17.4%). This rate increased to 60 of 130 (46.2%) among patients aged more than 80 years (P < .0001). The case fatality rate did not correlate with age in unstable patients.
CONCLUSIONS: The case fatality rate with pulmonary embolectomy in stable patients increases with age greater than 51 to 60 years and is high among the elderly. The case fatality rate with pulmonary embolectomy in unstable patients does not seem to be related to age.
Copyright © 2014 Elsevier Inc. All rights reserved.
Nicolas Meneveau, Marie-France Séronde, Marie-Cécile Blonde, Pierre Legalery, Katy Didier-Petit, Florent Briand, Fiona Caulfield, François Schiele, Yvette Bernard, Jean-Pierre Bassand
Management of unsuccessful thrombolysis in acute massive pulmonary embolism.
Chest. 2006 Apr;129(4):1043-50. doi: 10.1378/chest.129.4.1043.
Abstract/Text
BACKGROUND: The management of patients with acute massive pulmonary embolism (PE) who do not respond to fibrinolytic therapy remains unclear. We aimed to compare rescue surgical embolectomy and repeat thrombolysis in patients who did not respond to thrombolysis.
METHODS: We conducted a prospective single-center registry of PE patients who underwent thrombolytic therapy. Lack of response to thrombolysis within the first 36 h was prospectively defined as both persistent clinical instability and residual echocardiographic right ventricular dysfunction. Patients underwent surgical embolectomy or repeat thrombolysis, at the discretion of the attending physician. The clinical end point was a combined end point including recurrent PE, bleeding complications, or PE-related death, which was defined as death from recurrent PE or cardiogenic shock. Long-term adverse outcomes included death, recurrent thromboembolic events, and congestive heart failure.
RESULTS: From January 1995 to January 2005, 488 PE patients underwent thrombolysis, of whom 40 (8.2%) did not respond to thrombolysis. Fourteen patients were treated by rescue surgical embolectomy, and 26 were treated by repeat thrombolysis. There was no significant difference in baseline characteristics between the two groups. The in-hospital course was uneventful in 11 of the surgically treated patients (79%) and in 8 patients (31%) treated by repeat thrombolysis (p = 0.004). There was a trend for higher mortality in the medical group than in the surgical group (10 vs 1 deaths, respectively; p = 0.07). There were significantly more recurrent PEs (fatal and nonfatal) in the repeat-thrombolysis group (35% vs 0%, respectively; p = 0.015). While no significant difference was observed in number of major bleeding events, all bleeding events in the repeat-thrombolysis group were fatal. The rate of uneventful long-term evolution was the same in the two groups.
CONCLUSION: Rescue surgical embolectomy led to a better in-hospital course when compared with repeat thrombolysis in patients with massive PE who have not responded to thrombolysis. The transfer of patients who have not responded to thrombolysis to tertiary cardiac surgery centers could be considered as an alternative option.
Marzia Leacche, Daniel Unic, Samuel Z Goldhaber, James D Rawn, Sary F Aranki, Gregory S Couper, Tomislav Mihaljevic, Robert J Rizzo, Lawrence H Cohn, Lishan Aklog, John G Byrne
Modern surgical treatment of massive pulmonary embolism: results in 47 consecutive patients after rapid diagnosis and aggressive surgical approach.
J Thorac Cardiovasc Surg. 2005 May;129(5):1018-23. doi: 10.1016/j.jtcvs.2004.10.023.
Abstract/Text
OBJECTIVES: This study retrospectively reviews an aggressive multidisciplinary approach to the treatment of massive pulmonary embolism, centering on rapid diagnosis with contrast-enhanced computed tomography of the chest to define the location and degree of clot burden and transthoracic echocardiography to document right ventricular strain followed by immediate surgical intervention when appropriate.
METHODS: Between October 1999 through February 2004, 47 patients (30 men and 17 women; median age, 58 years; age range, 24-86 years) underwent emergency surgical embolectomy for massive central pulmonary embolism. The indications for surgical intervention were (1) contraindications to thrombolysis (21/47 [45%]), (2) failed medical treatment (5/47 [10%]), and (3) right ventricular dysfunction (15/47 [32%]). Preoperatively, 12 (26%) of 47 patients were in cardiogenic shock, and 6 (11%) of 47 were in cardiac arrest.
RESULTS: There were 3 (6%) operative deaths, 2 with preoperative cardiac arrest; 2 of these 3 patients required a right ventricular assist device. In 38 (81%) patients a caval filter was placed intraoperatively. Median length of stay was 11 days (range, 3-75 days). Median follow-up was 27 months (range, 2-50 months); follow-up was 100% complete in surviving patients. There were 6 (12%) late deaths, 5 of which were from metastatic cancer. Actuarial survival at 1 and 3 years' follow-up was 86% and 83%, respectively.
CONCLUSION: An aggressive approach to large pulmonary embolus, including rapid diagnosis and prompt surgical intervention, has improved results with surgical embolectomy. We now perform surgical pulmonary embolectomy not only in patients with large central clot burden and hemodynamic compromise but also in hemodynamically stable patients with right ventricular dysfunction documented by means of echocardiography.
Thierry Aymard, Alexander Kadner, Alexandra Widmer, Reto Basciani, Hendrik Tevaearai, Alberto Weber, Jürg Schmidli, Thierry Carrel
Massive pulmonary embolism: surgical embolectomy versus thrombolytic therapy--should surgical indications be revisited?
Eur J Cardiothorac Surg. 2013 Jan;43(1):90-4; discussion 94. doi: 10.1093/ejcts/ezs123. Epub 2012 Mar 30.
Abstract/Text
OBJECTIVES: The treatment of massive pulmonary embolism (PE) is a matter of debate. We present our institutional experience of patients suffering from massive PE with the aim of comparing the early results, the outcome and quality of life (QoL) between patients primarily assigned to either pulmonary surgical embolectomy (SE) or thrombolytic therapy (TL). A subgroup of patients (TS) with failed responses to TL requiring SE was separately analysed.
METHODS: All consecutive patients (January 2001-December 2007) with computed tomography (CT)-scan-confirmed massive bilateral central or paracentral PE were reviewed. All clinical data were retrieved from our patients' registry and completed by the evaluation of the CT-scan-derived right ventricle/left ventricle ratio (RV/LV ratio). Follow-up focused on clinical outcome and QoL was obtained.
RESULTS: Eighty patients were analysed including 28 SE (35%) and 52 TL (65%), of whom 11 (21%) required TS. Demographics and preoperative characteristics were similar between SE and TL. Analysis of the RV/LV ratio revealed a ratio of 1.66 for SE and 1.44 for TL. The early mortality rate was not significantly different between the two groups (SE: 3.6% versus TL: 13.5%), whereas early mortality was 27% in those patients treated initially with thrombolysis and subsequently requiring SE (TS-group). Severe bleeding complications were lower in the SE-group (3.6% versus 26.5% P = 0.013). Intracerebral bleeding rates and neurological events were not statistically different. After a mean follow-up of 63 ± 21 months, the mortality rate was 17.9% in the SE-group and 23.1% in the TL-group.
CONCLUSIONS: SE is an excellent treatment option in massive PE with comparable early mortality rates and significantly less bleeding complications than TL. Patients having surgery after inefficient thrombolysis have the worst early outcome. The RV/LV CT-scan ratio might serve as a predictor to differentiate patients, who could profit from direct surgical intervention than thrombolytic treatment attempts. Further studies are required to confirm these results.
Ikuo Fukuda, Satoshi Taniguchi, Kozo Fukui, Masahito Minakawa, Kazuyuki Daitoku, Yasuyuki Suzuki
Improved outcome of surgical pulmonary embolectomy by aggressive intervention for critically ill patients.
Ann Thorac Surg. 2011 Mar;91(3):728-32. doi: 10.1016/j.athoracsur.2010.10.086.
Abstract/Text
BACKGROUND: Acute massive pulmonary thromboembolism is a life-threatening disorder, and prompt treatment is necessary. We analyzed the outcome of pulmonary embolectomy for massive pulmonary embolism.
METHODS: Nineteen patients who underwent pulmonary embolectomy were retrospectively investigated. Average age of patients was 59 years, and 79% were female. Most patients had massive or submassive pulmonary thromboemboli dislodging into the main pulmonary trunk or bilateral main pulmonary arteries. Hemodynamics of most patients were unstable. Two patients required percutaneous cardiopulmonary support before embolectomy, and 4 required cardiopulmonary resuscitation. In 6 patients, thrombolysis was ineffective.
RESULTS: All patients underwent emergent pulmonary embolectomy. Operative mortality was 5.3%. No patients exhibited newly developed neurologic damage. Ten-year survival rate was 83.5% ± 8.7%.
CONCLUSIONS: Pulmonary embolectomy saves critically ill patients having acute massive pulmonary thromboembolism. We must evaluate pulmonary embolism patients with an algorithm that includes surgical embolectomy as one of several therapeutic options.
Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
Jeani Chang, Laurie D Elam-Evans, Cynthia J Berg, Joy Herndon, Lisa Flowers, Kristi A Seed, Carla J Syverson
Pregnancy-related mortality surveillance--United States, 1991--1999.
MMWR Surveill Summ. 2003 Feb 21;52(2):1-8.
Abstract/Text
PROBLEM/CONDITION: The risk of death from complications of pregnancy has decreased approximately 99% during the twentieth century, from approximately 850 maternal deaths per 100,000 live births in 1900 to 7.5 in 1982. However, since 1982, no further decrease has occurred in maternal mortality in the United States. In addition, racial disparity in pregnancy-related mortality ratios persists; since 1940, mortality ratios among blacks have been at least three to four times higher than those for whites. The Healthy People 2000 objective for maternal mortality of no more than 3.3 maternal deaths per 100,000 live births was not achieved during the twentieth century; substantial improvements are needed to meet the same objective for Healthy People 2010.
REPORTING PERIOD COVERED: This report summarizes surveillance data for pregnancy-related deaths in the United States for 1991-1999.
DESCRIPTION OF SYSTEM: The Pregnancy Mortality Surveillance System was initiated in 1987 by CDC in collaboration with state health departments and the American College of Obstetricians and Gynecologists Maternal Mortality Study Group. Health departments in the 50 states, the District of Columbia, and New York City provide CDC with copies of death certificates and available linked outcome records (i.e., birth certificates or fetal death certificates) of all deaths occurring during or within 1 year of pregnancy. State maternal mortality review committees, the media, and individual providers report a limited number of deaths not otherwise identified. Death certificates and relevant birth or fetal death certificates are reviewed by clinically experienced epidemiologists at CDC to determine whether they are pregnancy-related.
RESULTS: During 1991-1999, a total of 4,200 deaths were determined to be pregnancy-related. The overall pregnancy-related mortality ratio was 11.8 deaths per 100,000 live births and ranged from 10.3 in 1991 to 13.2 in 1999. The pregnancy-related mortality ratio for black women was consistently higher than that for white women for every characteristic examined. Older women, particularly women aged >/= 35 years and women who received no prenatal care, were at increased risk for pregnancy-related death. The distribution of the causes of death differed by pregnancy outcome. Among women who died after a live birth (i.e., 60% of the deaths), the leading causes of death were embolism and pregnancy-induced hypertension.
INTERPRETATION: The reported pregnancy-related mortality ratio has substantially increased during 1991-1999, probably because of improved ascertainment of pregnancy-related deaths. Black women continued to have a 3-4 times higher pregnancy-related mortality ratio than white women. In addition, pregnancy-related mortality has the largest racial disparity among the maternal and child health indicators. Reasons for this difference could not be determined from the available data.
PUBLIC HEALTH ACTIONS: Continued surveillance and additional studies should be conducted to monitor the magnitude of pregnancy-related mortality, to identify factors that contribute to the continuing racial disparity in pregnancy-related mortality, and to develop effective strategies to prevent pregnancy-related mortality for all women. In addition, CDC is working with state health departments, researchers, health-care providers, and other stakeholders to improve the ascertainment and classification of pregnancy-related deaths.
Andrea P MacKAy, Cynthia J Berg, Xiang Liu, Catherine Duran, Donna L Hoyert
Changes in pregnancy mortality ascertainment: United States, 1999-2005.
Obstet Gynecol. 2011 Jul;118(1):104-10. doi: 10.1097/AOG.0b013e31821fd49d.
Abstract/Text
OBJECTIVE: To estimate mortality ratios for all reported pregnancy deaths in the United States, 1999-2005, and to estimate the effect of the 1999 implementation of International Classification of Diseases, Tenth Revision (ICD-10) and adoption of the U.S. Standard Certificate of Death, 2003 Revision, on the ascertainment of deaths resulting from pregnancy.
METHODS: We combined information on pregnancy deaths from the National Vital Statistics System and the Pregnancy Mortality Surveillance System to estimate maternal (during or within 42 days of pregnancy) and pregnancy-related (during or within 1 year of pregnancy) mortality ratios (deaths per 100,000 live births). Data for 1995-1997, 1999-2002, and 2003-2005 were compared in order to estimate the effects of the change to ICD-10 and the inclusion of a pregnancy checkbox on the death certificate.
RESULTS: The maternal mortality ratio increased significantly from 11.6 in 1995-1997 to 13.1 for 1999-2002 and 15.3 in 2003-2005; the pregnancy-related mortality ratio increased significantly from 12.6 to 14.7 and 18.1 during the same periods. Vital statistics identified significantly more indirect maternal deaths in 2002-2005 than in 1999-2002. Between 2002 and 2005, mortality ratios increased significantly among 19 states using the revised death certificate with a pregnancy checkbox; ratios did not increase in states without a checkbox.
CONCLUSION: Changes in ICD-10 and the 2003 revision of the death certificate increased ascertainment of pregnancy deaths. The changes may also have contributed to misclassification of some deaths as maternal in the vital statistics system. Combining data from both systems estimates higher pregnancy mortality ratios than from either system individually.
M S Levy, F Spencer, J S Ginsberg, J A M Anderson
Reading between the (Guidelines). Management of submassive pulmonary embolism in the first trimester of pregnancy.
Thromb Res. 2008;121(5):705-7. doi: 10.1016/j.thromres.2007.07.001. Epub 2007 Aug 17.
Abstract/Text
M S To, B J Hunt, C Nelson-Piercy
A negative D-dimer does not exclude venous thromboembolism (VTE) in pregnancy.
J Obstet Gynaecol. 2008 Feb;28(2):222-3. doi: 10.1080/01443610801915975.
Abstract/Text
Yugo Yamashita, Daiki Hira, Makiko Morita, Yurie Katsube, Masahito Takakura, Hiroko Tomotaki, Seiichi Tomotaki, Wei Xiong, Hiroki Shiomi, Takahiro Horie, Satoshi Ueshima, Tomoyuki Mizuno, Tomohiro Terada, Koh Ono
Potential treatment option of rivaroxaban for breastfeeding women: A case series.
Thromb Res. 2024 May;237:141-144. doi: 10.1016/j.thromres.2024.04.003. Epub 2024 Apr 5.
Abstract/Text
The use of direct oral anticoagulants (DOACs) in breastfeeding women is currently challenging due to limited safety data for breastfeeding infants, and there have been no previous studies on the drug concentration in breastfeeding infants. We treated 2 patients (one case was twin pregnancy) with venous thromboembolisms in breastfeeding women administered rivaroxaban at our institution. Blood samples from the mothers and breastmilk samples were collected at time 0 and 2 h after the rivaroxaban administration, breastfeeding was conducted 2 h after the rivaroxaban administration, and blood samples from the infants were collected 2 h after breastfeeding (4 h after maternal rivaroxaban administration). The milk-to-plasma (M:P) ratios were 0.27 in Case 1 and 0.32 in Case 2. The estimated relative infant dose (RID) was 0.82 % in Case 1 Children 1 and 2, and 1.27 % in Case 2. The rivaroxaban concentration in the infant plasma was below the lower limit of quantification in all infants. In addition, even in the high-exposure case simulation based on 5 days of breastfeeding in Case 2, the infant plasma concentration level was below the lower limit of quantification. At 3 months of follow-up, breastfeeding was continued, and all infants grew and developed without any health problems including bleeding events. The current case series showed that there were no pharmacokinetic or clinical concerns for breastfeeding women or breastfed infants, and provides support for rivaroxaban as a safe treatment option for these patients.
Copyright © 2024 Elsevier Ltd. All rights reserved.
