重度静脉血栓栓塞治疗指南

ISSN: 1524-4539 Copyright © 2011 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX DOI: 10.1161/CIR.0b013e318214914f published online Mar 21, 2011; Circulation Vascular Biology Peripheral Vascular Disease, and Council on Arteriosclerosis, Thrombosis and Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Zierler and on behalf of the American Heart Association Council on Michaels, Patricia Thistlethwaite, Suresh Vedantham, R. James White, Brenda K. Goldenberg, Samuel Z. Goldhaber, J. Stephen Jenkins, Jeffrey A. Kline, Andrew D. Michael R. Jaff, M. Sean McMurtry, Stephen L. Archer, Mary Cushman, Neil A Scientific Statement From the American Heart Association Hypertension:Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Management of Massive and Submassive Pulmonary Embolism, Iliofemoral http://circ.ahajournals.org located on the World Wide Web at: The online version of this article, along with updated information and services, is http://www.lww.com/reprints Reprints: Information about reprints can be found online at journalpermissions@lww.com 410-528-8550. E-mail: Fax:Kluwer Health, 351 West Camden Street, Baltimore, MD 21202-2436. Phone: 410-528-4050. Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters http://circ.ahajournals.org/subscriptions/ Subscriptions: Information about subscribing to Circulation is online at by on May 20, 2011 circ.ahajournals.orgDownloaded from AHA Scientific Statement Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension A Scientific Statement From the American Heart Association Michael R. Jaff, DO, Co-Chair; M. Sean McMurtry, MD, PhD, Co-Chair; Stephen L. Archer, MD, FAHA; Mary Cushman, MD, MSc, FAHA; Neil Goldenberg, MD, PhD; Samuel Z. Goldhaber, MD; J. Stephen Jenkins, MD; Jeffrey A. Kline, MD; Andrew D. Michaels, MD, MAS, FAHA; Patricia Thistlethwaite, MD, PhD; Suresh Vedantham, MD; R. James White, MD, PhD; Brenda K. Zierler, PhD, RN, RVT; on behalf of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Peripheral Vascular Disease, and Council on Arteriosclerosis, Thrombosis and Vascular Biology Venous thromboembolism (VTE) is responsible for thehospitalization of �250 000 Americans annually and represents a significant risk for morbidity and mortality.1 Despite the publication of evidence-based clinical practice guidelines to aid in the management of VTE in its acute and chronic forms,2,3 the clinician is frequently confronted with manifestations of VTE for which data are sparse and optimal management is unclear. In particular, the optimal use of advanced therapies for acute VTE, including thrombolysis and catheter-based therapies, remains uncertain. This report addresses the management of massive and submassive pul- monary embolism (PE), iliofemoral deep vein thrombosis (IF- DVT), and chronic thromboembolic pulmonary hypertension (CTEPH). The goal is to provide practical advice to enable the busy clinician to optimize the management of patients with these severe manifestations of VTE. Although this document makes recommendations for management, optimal medical decisions must incorporate other factors, including patient wishes, quality of life, and life expectancy based on age and comorbidities. The appropriateness of these recommendations for a specific patient may vary depending on these factors and will be best judged by the bedside clinician. Methods A writing group was established with representation from the Council on Peripheral Vascular Disease and Council on Cardiopulmonary, Critical Care, Perioperative and Resusci- tation of the American Heart Association and vetted by American Heart Association leadership. All writing group members were required to disclose all relationships with industry and other entities relevant to the subject. The writing group was subdivided into the 3 areas of statement focus, and each subgroup was led by a member with content expertise (deep venous thrombosis [S.V.], pulmonary embolism [S.Z.G.], and chronic thromboembolic pulmonary hyperten- sion [P.A.T.]). The writing groups systematically reviewed and summarized the relevant published literature and incor- porated this information into a manuscript with draft recom- mendations. Differences in opinion were dealt with through a face-to-face meeting and subsequently through electronic and telephone communications. The final document reflects the consensus opinion of the entire committee. Areas of uncer- tainty are also noted in hopes that both basic and clinical research will advance knowledge in this area. The American Heart Association Levels of Evidence were adopted (Table The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 5, 2011. A copy of the statement is available at http://www.americanheart.org/presenter.jhtml?identifier�3003999 by selecting either the “topic list” link or the “chronological list” link. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com. The American Heart Association requests that this document be cited as follows: Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg NA, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK; on behalf of the American Heart Association Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation, Council on Peripheral Vascular Disease, and Council on Arteriosclerosis, Thrombosis and Vascular Biology. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation. 2011;123:●●●–●●●. Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development, visit http://www.americanheart.org/presenter.jhtml?identifier�3023366. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.americanheart.org/presenter.jhtml?identifier� 4431. A link to the “Permission Request Form” appears on the right side of the page. (Circulation. 2011;123:00-00.) © 2011 American Heart Association, Inc. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIR.0b013e318214914f 1 by on May 20, 2011 circ.ahajournals.orgDownloaded from 1). External reviewers appointed by the American Heart Association independently reviewed the document. Each recommendation required a confidential vote by the writing group members after external review of the document. Any writing group member with a relationship with industry relevant to the recommendation was recused from the voting on that recommendation. Disclosure of relationships is in- cluded in this document (Writing Group Disclosure Table). Massive, Submassive, and Low-Risk PE Massive PE Outcomes in acute PE vary substantially depending on patient characteristics.4,5 To tailor medical and interventional thera- pies for PE to the appropriate patients, definitions for sub- groups of PE are required. The qualifiers “massive,” “sub- massive,” and “nonmassive” are often encountered in the literature, although their definitions are vague, vary, and lead to ambiguity.6 Although it is attractive to stratify types of acute PE on the basis of the absolute incidence of complica- tions such as mortality, this approach is complicated by comorbidities; for example, a nonmassive acute PE might be associated with a high risk for complications in a patient with many comorbidities,7 such as obstructive airway disease or congestive heart failure. Massive PE traditionally has been defined on the basis of angiographic burden of emboli by use of the Miller Index,8 but this definition is of limited use. Registry data support the assertion that hypotension and circulatory arrest are associated with increased short-term mortality in acute PE. In the International Cooperative Pulmonary Embolism Registry (ICOPER), the 90-day mor- tality rate for patients with acute PE and systolic blood pressure �90 mm Hg at presentation (108 patients) was Table 1. Applying Classification of Recommendations and Level of Evidence * Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. † For recommendations (Class I and IIa; Level of Evidence A and B only) regarding the comparative effectiveness of one treatment with respect to another, these words or phrases may be accompanied by the additional terms “in preference to” or “to choose” to indicate the favored intervention. For example, “Treatment A is recommended in preference to Treatment B for …” or “It is reasonable to choose Treatment A over Treatment B for ….” Studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated. 2 Circulation April 26, 2011 by on May 20, 2011 circ.ahajournals.orgDownloaded from 52.4% (95% confidence interval [CI] 43.3% to 62.1%) versus 14.7% (95% CI 13.3% to 16.2%) in the remainder of the cohort.9 Similarly, in the Germany-based Management Strategy and Prognosis of Pulmonary Embolism Registry (MAPPET) of 1001 patients with acute PE, in-hospital mortality was 8.1% for hemodynamically stable patients versus 25% for those pres- enting with cardiogenic shock and 65% for those requiring cardiopulmonary resuscitation.10 Both the Geneva and Pulmo- nary Embolism Severity Index (PESI) clinical scores identify hypotension (blood pressure �100 mm Hg) as a significant predictor of adverse prognosis.7,11 We propose the following definition for massive PE: Acute PE with sustained hypotension (systolic blood pressure �90 mm Hg for at least 15 minutes or requiring inotropic support, not due to a cause other than PE, such as arrhythmia, hypovolemia, sepsis, or left ventricular [LV] dysfunction), pulselessness, or persistent profound bradycardia (heart rate �40 bpm with signs or symptoms of shock). Submassive PE Several techniques have been used to identify subjects at increased risk for adverse short-term outcomes in acute PE (Table 2). These data are based on series of adult patients; there are limited data for prognosis of PE for pediatric patients. Clinical Scores Registry data support the idea that clinical features, including age and comorbidities, influence prognosis in acute PE.4,5,71 These features have been incorporated into clinical scores to estimate prognosis,7,11–17,72,73 including the Geneva and PESI scores.7,11 Clinical scores do predict adverse outcomes in acute PE independent of imaging or biomarkers.69 Echocardiography Echocardiography identifies patients at increased risk of adverse outcomes from acute PE in many studies,4,5,18–23,74–81 although there is diversity in criteria for right ventricular (RV) dysfunction on echocardiography. Sanchez et al82 per- formed a (selective) meta-analysis and calculated an odds ratio for short-term mortality for RV dysfunction on echocar- diography (defined variably; Table 2) of 2.53 (95% CI 1.17 to 5.50). Computed Tomographic (CT) Scan CT scan measurements of RV dilation predict adverse short- term events,25,33 including in-hospital death,27 30-day mortal- ity,26 and mortality at 3 months.28 The criterion for RV dilation has varied among studies; an RV diameter divided by LV diameter �0.9 in a 4-chamber view was used by Quiroz et al25 and Schoepf et al.26 Results from 1 large cohort of 1193 patients suggested that ventricular septal bowing was predictive of short-term mortality but that the ratio of RV diameter to LV diameter was not.29 This same group found that RV diameter divided by LV diameter was predictive of other adverse outcomes, including admission to an intensive care unit.24 An additional study did not support RV dilation as being predictive of adverse prognosis, although a 4-chamber view was not used.32 Clot burden measured by CT angiogra- phy does not predict adverse prognosis.30 Elevated Troponins Elevated troponins, including troponin I and troponin T, are associated with adverse prognosis in acute PE.43–55,83,84 Becattini et al85 summarized the literature in a meta-anal- ysis and demonstrated that in submassive PE, troponin elevations had an odds ratio for mortality of 5.90 (95% CI 2.68 to 12.95). Elevated Natriuretic Peptides Elevated natriuretic peptides, including brain natriuretic peptide (BNP)34 –38,86 and N-terminal pro-BNP,39 – 42 have been shown to be predictive of adverse short-term out- comes in acute PE. In the meta-analysis by Sanchez et al,82 the odds ratios for short-term mortality for BNP or N-terminal pro-BNP elevations in patients with submas- sive PE were 9.51 (95% CI 3.16 to 28.64) and 5.74 (95% CI 2.18 to 15.13), respectively. Cavallazzi et al87 and Klok et al88 also showed that BNP and N-terminal pro-BNP elevations were predictive of mortality. Other novel bio- markers, including D-dimer and heart-type fatty acid– binding protein, also have prognostic value.89 –92 Electrocardiography Electrocardiography helps identify patients at risk of adverse outcomes in acute PE. Abnormalities reported with acute PE include sinus tachycardia, atrial arrhythmias, low voltage, Q waves in leads III and aVF (pseudoinfarction), S1Q3T3 pattern, Qr pattern in V1, P pulmonale, right-axis deviation, ST-segment elevation, ST-segment depression, QT prolongation, and incomplete or complete right bundle-branch block.30,93–110 Of these, sinus tachycardia, new-onset atrial arrhythmias, new right bundle-branch block (complete or incomplete), Qr pattern in V1, S1Q3T3, negative T waves in V1 through V4, and ST-segment shift over V1 through V4 have been shown to correlate with worse short-term prognosis in acute PE.101–104,106 –110 Hybrid Studies Hybrid studies, which involve multiple prognostic vari- ables,14,30,37,54,56 –70,111–113 demonstrate that combinations of RV dysfunction, elevated natriuretic peptides, or ele- vated troponin are markers of adverse prognosis. Although the techniques described above have utility for predicting prognosis in acute PE, clinical judgment is required to determine which of these is appropriate for an individual patient. We propose the following definition for submassive PE: Acute PE without systemic hypotension (systolic blood pres- sure �90 mm Hg) but with either RV dysfunction or myo- cardial necrosis. ● RV dysfunction means the presence of at least 1 of the following: — RV dilation (apical 4-chamber RV diameter divided by LV diameter �0.9) or RV systolic dysfunction on echocardiography — RV dilation (4-chamber RV diameter divided by LV diameter �0.9) on CT — Elevation of BNP (�90 pg/mL) — Elevation of N-terminal pro-BNP (�500 pg/mL); or Jaff et al Challenging Forms of Venous Thromboembolic Disease 3 by on May 20, 2011 circ.ahajournals.orgDownloaded from Table 2. Studies of Prognosis in Acute PE Studies by Type of Variable Tested and First Author Year Published No. of Subjects Included Subjects Variable(s) Tested Outcome Effect Clinical scores Wicki11 2000 296 Acute PE Geneva score Death, recurrent VTE, or major bleeding at 3 mo OR 15.7 for high risk vs low risk (95% CI not reported) Nendaz12 2004 199 Acute PE Geneva score Death, recurrent VTE, or major bleeding at 3 mo OR 7.2 for high risk vs low risk (95% CI not reported) Aujesky7 2005 15 531 Acute PE PESI clinical score 30-d mortality OR 29.2 for class V vs I (95% CI not reported) Uresandi13 2007 681 Outpatients with acute PE Spanish clinical score Death, recurrent VTE, or major/minor bleeding at 10 d OR 4.7 for high risk vs low risk (95% CI not reported) Jime´nez14 2007 599 Acute PE PESI and Geneva scores 30-d mortality OR 4.5 for PESI class V, OR 3.1 for Geneva high risk (95% CI not reported) Donze´15 2008 357 Acute PE PESI clinical score 90-d mortality OR 12.4 for PESI class III–V vs I–II (95% CI not reported) Choi16 2009 90 Acute PE PESI clinical score 30-d mortality OR 19.8 for PESI class V vs PESI I Ruı´z-Gime´nez17 2008 13 057 Acute PE Bleeding risk score Major bleeding at 3 mo LR 2.96 (95% CI 2.18–4.02) for high risk Echocardiography Ribeiro18 1997 126 Acute PE Moderate-severe RV systolic dysfunction on echo In-hospital mortality OR � (no deaths observed with normal RV function) Goldhaber4 1999 2454 Acute PE RV hypokinesis on echo (in addition to age �70 y, cancer, CHF, COPD, hypotension, and tachypnea) All-cause mortality at 3 mo HR 2.0 (95% CI 1.2–3.2) for RV hypokinesis Grifoni5 2000 209 Acute PE �1 of RV dilation (EDD �30 mm or RVEDD/LVEDD ratio �1 in apical 4-chamber view), paradoxical septal motion, or RVSP �30 mm Hg In-hospital all-cause mortality OR 4.7 (95% CI not reported) Vieillard-Baron19 2001 161 “Massive” PE defined as at least 2 lobar PAs occluded RVEDA/LVEDA �0.6 on echo In-hospital all-cause mortality NS in multivariate model Kucher20 2005 1035 Acute PE with systolic BP �90 mm Hg RV hypokinesis on echo 30-d mortality HR 1.94 (95% CI 1.23–3.06) Jiang21 2007 57 “Normotensive” acute PE RV dilation, PASP �30 mm Hg, TR jet velocity �2.8 m/s In-hospital mortality OR 5.6 (95% CI not reported) Fre´mont22 2008 950 Acute PE RVEDD/LVEDD �0.9 In-hospital mortality OR 2.66, P�0.01 (95% CI not reported) Kjaergaard23 2009 283 “Nonmassive” acute PE PA acceleration time All-cause mortality at 1 y HR 0.89 (95% CI 0.83–0.97) CT scan Araoz24 2003 173 Acute PE RV/LV diameter ratio, ventricular septal bowing, clot burden In-hospital mortality All variables NS Quiroz25 2004 63 Acute PE RVD/LVD �0.9 (reconstructed 2- and 4-chamber views studied) Adverse events (30-d mortality, CPR, ventilation, pressors, thrombolysis, or embolectomy) OR 4.02 (95% CI 1.06 to 15.19) for RVD/LVD �0.9 in 4-chamber view Schoepf26 2004 431 Acute PE RVD/LVD �0.9 in reconstructed 4-chamber view 30-d mortality HR 5.17 (95% CI 1.63–16.35) Ghuysen27 2005 82 Acute PE RVD/LVD �1.46 In-hospital mortality OR 5.0 (95% CI not reported) van der Meer28 2005 120 Acute PE RVD/LVD �1.0 in short-axis view Mortality at 3 mo Hazard not reported, but negative predictive value was 100% (95% CI 93.4–100) Araoz29 2007 1193 Acute PE Ventricular septal bowing, RVD/LVD, clot burden 30-d mortality No consistent predictor variable Subramaniam30 2008 523 Acute PE Clot burden and electrocardiography score All-cause mortality at 1 y NS for both Findik31 2008 33 Massive acute PE (systolic BP �90 mm Hg) RV dysfunction, main PA diameter, ventricular septal shape, clot burden In-h