急性肺动脉栓塞及进展-心内科何国祥

,急性肺栓塞诊疗指南及进展Guidelines and Progress on the Diagnosis and Management of Acute Pulmonary Embolism,Southwest Hospital,何国祥Prof. Guoxiang HE第三军医大学西南医院重庆市介入心脏病学研究所Southwest HospitalThe Third Military Medical UniversityChongqing Institute of Interventional Cardiology,Southwest Hospital,Update in 2010,中国急性肺血栓栓塞症诊断治疗专家共识,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,1、背景2、临床评估3、定量评估4、治疗 抗凝 溶拴 手术 导管治疗5、妊娠PE6、非血栓PE,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,1、背景2、临床评估3、定量评估4、治疗 抗凝 溶拴 手术 导管治疗5、妊娠PE6、非血栓PE,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,FIG 1. Venous thromboembolism (VTE)/100,000 population/year from 1990 through 1999.(Data from Stein et al.3-5),Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,FIG 2. Deep venous thrombosis (DVT)/100,000 population/year shown according to age for the year 1999.6,7 (Reprinted with permission.10),Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,FIG 3. Pulmonary embolism (PE)/100,000 population/year shown according to age for the year 1999. (Data from Stein et al.5,6) (Reprinted with permission.10),Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,FIG 12. Estimated case fatality rates for PE according to decades of age. (Reprinted with permission.23),Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,FIG 4. PE and DVT in children. (Data from Stein et al.7),Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Major risk factors for venous thrombosis, Major surgery Orthopaedic surgery to lower limb/lower limb trauma History of previous venous thrombosis Cancer Pregnancy/puerperium Reduced mobility major illness with prolonged bed rest Age 70 years Thrombophilias: antithrombin deficiency protein C deficiency protein S deficiency antiphospholipid antibodies,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,1、背景2、临床评估3、定量评估4、治疗 抗凝 溶拴 手术 导管治疗5、妊娠PE6、非血栓PE,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,TABLE 5. Electrocardiographic manifestations: patients without prior cardiac or pulmonary disease,Data from Stein et al.29,57 Reprinted with permission.10Some patients had more than 1 abnormality.,Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,TABLE 6. Plain chest radiograph in patients with acute pulmonary embolism and no prior cardiopulmonary disease,Data are from Stein et al.29,63 Reprinted with permission.10aAmong patients with a pleural effusion, 86% had only blunting of the costophrenic angle.None had a pleural effusion that occupied more than one third of a hemithorax.bProminent central pulmonary artery and decreased pulmonary vascularity.,Guidelines and Progress on the Diagnosis and Management of Acute PE,肺实质异常,肺不张/萎陷,肺实变,胸水,Southwest Hospital,FIGURE 2. V/QSPECT for the detection of pulmonary embolism,V/QSPECT thermal imaging coronal posterior sections in a female patient show multiple large pulmonary-ventilatory areas of mismatch that indicate pulmonary emboli that involve the upper and lower lobes of the right lung (white arrows).V/QSPECT, ventilation and perfusion single photon emission computed tomography.,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,FIG 19. Relative use of diagnostic imaging tests in patients hospitalized with PE from 1979 through 2006. V/Q, ventilation/perfusion; ANGIOS, pulmonary angiograms. (Reprinted with permission.10),Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,FIG 20. CT pulmonary angiogram showing PE in the right pulmonary artery.,Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,FIG 21. CT venous phase image showing right popliteal vein thrombosis (arrow).,Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Three images from a single computed tomography pulmonary angiography (CTPA) study performed with a high clinical suspicion of pulmonary embolism (PE). Image 1 demonstrates a large PE in the proximal right pulmonary artery. Image 2 shows a significant concurrent pneumothorax. Image 3 demonstrates an RV/LV ratio 1 signifying significant right ventricular (RV) dysfunction. Together these images show the high utility of CTPA in diagnosis/exclusion of PE, diagnosis/exclusion of differential diagnoses, and in risk stratifying a patient so as to guide therapy.,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Causes of a raised D-dimer venous thromboembolic disease increasing age cancer infection haematoma post surgery inflammation pregnancy peripheral vascular disease liver disease,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,The Thrombo-Embolism Lactate Outcome Study 血栓-栓塞乳酸盐转归研究 Prognostic Value of Plasma Lactate Levels Among Patients With Acute Pulmonary Embolism 血浆乳酸盐水平在PE患者中的预后价值,Ann Emerg Med. 2012;xx:xxx,Table 2. Description of 30-day outcome of patients investigated (n=270).*,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Figure 3. All-cause death and composite endpoint incidence in patients with increasing values of plasma lactate level.,乳酸盐水平与全因死亡和复合终点,Ann Emerg Med. 2012;xx:xxx,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Figure 4. Cox proportional hazard analysis of the relationship between plasma lactate level greater than or equal to 2 mmol/L and outcome in 270 patients withacute pulmonary embolism.,Ann Emerg Med. 2012;xx:xxx,全因死亡,复合终点,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Figure 5. Receiver operating characteristic curve analysis of plasma lactate level, troponin I level, and sPESI values in 270 patients with acute pulmonary embolism.,Ann Emerg Med. 2012;xx:xxx,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Elevated Heart-Type Fatty Acid-Binding Protein Levels on Admission Predict an Adverse Outcome in Normotensive Patients With Acute Pulmonary Embolism 心肌脂肪酸结合蛋白水平升高预测血压正常的APE病人不良转归,(J Am Coll Cardiol 2010;55:21507),Figure 1 Prognostic Sensitivity and Specificity of H-FABP, cTnT, and NT-proBNP,Receiver operating characteristic curves for heart-type fatty acid-binding protein (H-FABP), cardiac troponin T (cTnT), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels on admission with regard to a complicated 30-day outcome. AUC area under the curve.,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Figure 2 Combination of H-FABP With Clinical ParametersThe number of patients with complications and the overall number of patients are given, along with percentages, for each column. H-FABP heart-type fattyacid binding protein; HR heart rate; RV right ventricular.,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Figure 3 Probability of Long-Term Survival in Patients With or Without Elevation of H-FABP, cTnT, and NT-proBNPBiomarker levels were dichotomized, and elevated concentrations were defined as those 6 ng/ml for H-FABP, 0.04 ng/ml for cTnT, and 1,000 pg/ml forNT-proBNP. Red lines elevated values; blue lines normal values; p values were calculated by the log-rank test. Abbreviations as in Figure 1.,JACC 2010; 55(19): 21507,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Fig. 1. Pathophysiology of right ventricular dysfunction during acute pulmonary embolism. RV: Right ventricule; LV: Left ventricle; TXA2: Thromboxane-A2; ET: Endothelin; PGF2a: Prostaglandin F2a ; PGI2: Prostacyclin. Grey arrow indicates that all constituted a vicious cycle. Black arrow indicates pathophysiology change.,J Med Coll PLA 2010；25：235-246,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Table 2 Echocardiographic risk assessment in PE1. Diagnostic criteria for RV dysfunction RV功能不全的标准 A. RV wall hypokinesis -Moderate or severe -McConnells sign regional RV hypokinesis in which the apex is spared B. RV dilatation -End-diastolic diameter 30 mm in parastemal view -RV larger than LV in sobcostal or apical view -Increased tricuspid velocity 26 m/sec -Paradoxical RV septal systolic motion C. Pulmonary artery hypertension -Pulmonary artery systolic pressure 30 mmHg -Dilated IVC with lack of respiratory collapse2. Other factors associated with increased mortality A. Patent foramen ovale B. Free-floating night-heat thrombus,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Fig. 1 Physician assessment of patients with PE.,Guidelines and Progress on the Diagnosis and Management of Acute PE,PE的临床评估,Southwest Hospital,1、背景2、临床评估3、定量评估4、治疗 抗凝 溶拴 手术 导管治疗5、妊娠PE6、非血栓PE,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Assessment of clinical probability,Revised Geneva Score PointsAge 60 years 1Previous VTE 3Surgery/fracture lower limb in last month 2Active malignancy 2Unilateral lower limb pain 3Haemoptysis 2Heart rate 7594 3Heart rate 95 5Pain on lower limb deep venous palpation andunilateral oedema 4Clinical probability Total points Low 03 Intermediate 410 High 10,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Modified Wells score 6 PointsSymptoms of a DVT 3No alternative diagnosis 3Heart rate 100 1.5Immobilization or surgery in the previous month 1.5Previous VTE 1.5Malignancy 1.5Haemoptysis 1.5Score 4 or less, PE unlikely,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,TABLE 12. Positive predictive values of CTA and CTA/CTV in relation to prior clinical assessment,Only patients with a reference test diagnosis by V/Q scan or conventional pulmonary DSA were included.Abbreviations: CTA, computed tomographic pulmonary angiography; CTV, venous phase venogram. Reprinted with permission.14,Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,TABLE 13. Negative predictive values of CTA and CTA/CTV in relation to prior clinical assessment,Only patients with a reference test diagnosis by V/Q scan or conventional pulmonary DSA were included.Abbreviations: CTA, computed tomographic pulmonary angiography; CTV, venous phase venogram.Reprinted with permission.14,Curr Probl Cardiol 2010;35:314-376,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,BTS score PointsIs a PE a reasonable diagnosis? 1PE的诊断合理? Is an alternative diagnosis less likely? 1可能性小? Is a major risk factor present? 1存在主要危险因素? 1 point, low clinical probability; 2 points, intermediate clinical probability;3 points, high clinical probability.,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,1、背景2、临床评估3、定量评估4、治疗 抗凝 溶拴 手术 导管治疗5、妊娠PE6、非血栓PE,Guidelines and Progress on the Diagnosis and Management of Acute PE,Acute Pulmonary Artery Embolism,Southwest Hospital,Fig. 3 Pathophysiology of RV dysfunction and death in PE.,Southwest Hospital,循环的维持：Increasing MAP (i.e. filling and pressor support) Reducing RVPm (i.e. reducingPAPs/pulmonary vascular) resistance(selective pulmonary vasodilators (e.g. nitric oxide or inhaled prostacyclin) though these may result in systemic hypotension增加MAP，降低RVPm，尽管可以导致体循环低血压Noradrenaline can counteract these concerns to a degree and is also the preferred inotrope for its concomitant beneficial alpha and beta-adrenergic effects on MAP and cardiac output respectively去甲肾上腺素：增加MAP 和 COInotropes that have systemic vasodilatory effects (such as milrinone ordobutamine) which may increase cardiac output without increasingMAP and therefore not significantly improve RVCPP具有体循环血管扩张作用的药物（米力农、多巴酚丁胺）可增加CO，但不增加MAP，而不显著改善RVCPP Right ventricular coronary perfusion pressure (RVCPP = MAP - RVPm),ANAESTHESIA AND INTENSIVE CARE MEDICINE 2010；11:12,Acute Pulmonary Artery Embolism,Southwest Hospital,Anticoagulation 抗凝：有充分理由支持诊断PE：开始全剂量的LMUH治疗由影像学证实和确诊PE：停LMUH 改为warfarin（INR=2-3，目标=2.5） 为门诊病人安排监测 INR,Acute Pulmonary Artery Embolism,Southwest Hospital,Suggested dosing, heparin therapy,ANAESTHESIA AND INTENSIVE CARE MEDICINE 2010；11:12,Acute Pulmonary Artery Embolism,Southwest Hospital,How long to treat?,根据PE的原因而异 通常6W-3M 可能足够 病因持续存在: 抗凝持续 原发/先天性PE,一旦停止治疗,复发率410%/年，4年以上远期事 件率20% 因此, I级事件后应终身抗凝治疗,但需要权衡治疗的获益与风险 严重出血(颅内出血；腹膜后出血；Hb降低需要输血者）： 75岁 1% /年 75岁 5% /年 决策治疗疗程前与病人 / 家属讨论利弊是明智/必要的,Acute Pulmonary Artery Embolism,Southwest Hospital,Fig. 2. Percentage and size of residual pulmonary thrombi. Greater, similar and smaller occlusion mean bigger, same and lesser size of pulmonary thrombi respectively as seen in second computed tomography.,Eur J Int Med 2012；23 ：379383,Eur J Int Med 2012；23 ：379383,Residual pulmonary thromboemboli after acute pulmonary embolism 继发于肺栓塞的残余肺血栓,Acute Pulmonary Artery Embolism,Southwest Hospital,Eur J Int Med 2012；23 ：379383,Residual pulmonary thromboemboli after acute pulmonary embolism 继发于肺栓塞的残余肺血栓,Acute Pulmonary Artery Embolism,Southwest Hospital,Eur J Int Med 2012；23 ：379383,Residual pulmonary thromboemboli after acute pulmonary embolism 继发于肺栓塞的残余肺血栓,Acute Pulmonary Artery Embolism,Southwest Hospital,Lifelong treatment is appropriate if:,The initial PE was lifethreateningPE威胁生存The patient has significant cardiorespiratory disease患者有显著的心肺疾病Whereby a further, even small, PE could have fatal consequences;or the patient has a second, unprovoked eventPE可能有致命性后果，或有再次无缘无故的事件,Acute Pulmonary Artery Embolism,Southwest Hospital,INR 达标: PE的复发是罕见的如果复发：增加 warfarin、增大目标 INR 癌症患者（复发更常见）：转换为LMWH在抗凝治疗中仍存在DVT，或抗凝禁忌：腔静脉滤器（可回收式）,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,抗凝：严重出血并发症 3%漏诊PE：死亡风险 30%提示：确诊的PE、临床高度PE风险者均应抗凝，除非有明确禁忌症,ANAESTHESIA AND INTENSIVE CARE MEDICINE 2010；11:12,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,New Drug ReviewDabigatran Etexilate: An Oral Direct Thrombin Inhibitor forthe Management of Thromboembolic Disorders 达比加群：口服的直接凝血酶抑制剂,Clin Ther. 2012;34:766787,Table I. Pertinent drug interactions with dabigatran,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,Table II. Pertinent clinical studies on the use of dabigatran.,Guidelines and Progress on the Diagnosis and Management of Acute PE,Southwest Hospital,BISTRO I Boehringer Ingelheim Study in Thrombosis I; DE dabigatran etexilate; DVT deep vein thrombosis; PE pulmonary embolism; QD daily; RE-NOVATE Prevention of Venous ThromboembolismAfter Total Hip Replacement; VTE venous thromboembolism; RE-MODEL Thromboembolism Prevention After Knee Surgery; RE-MOBILIZE Dabigatran Versus Enoxaparin in Preventing Venous ThromboembolismFollowing Total Knee Arthroplasty; RE-COVERDabigatran Versus Warfarin in