Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Guidelines on the diagnosis and management of acute pulmonary embolism The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC) 2008 Caso Clinico Uomo di 62 anni si presenta con una storia di dispnea ingravescente che dura da 5 giorni, con ortopnea, dopo un viaggio di lavoro di 3 giorni. Esame fisico: Fc 102 bpm.PA 110/60 mmHg Sat. O2 86% in aria Distensione delle giugulari Non soffi cardiaci Estremità normali .Polmoni : ndn D-dimero elevato ( 5,13 mg/L-V.N.< 0,5).Troponina T < 0,01 mcg/L. TC : trombosi multipla delle aa polmonari e dilatazione del Vdx Come trattare questo paziente ? ESC GuideLine 2008: Acute Pulmonary Embolism European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism EPIDEMIOLOGY •PE and DVT are two clinical presentations of venous thromboembolism (VTE) and share the same predisposing factors •In most cases PE is a consequence of DVT •Among patients with proximal DVT , about 50% have an associated usually clinically asymptomatic PE at lung scan •In about 70% of patients with PE, DVT can be found in the lower limbs if sensitive diagnostic methods are used European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism EPIDEMIOLOGY •According to prospective cohort studies, the acute case fatality rate for PE ranges from 7 to 11% •Also, recurrent episodes are about three times more likely to be PE after an initial PE than after an initial DVT (about 60% after PE vs. 20% after DVT) •The prevalence of PE among hospitalized patients in the United States, according to data collected between 1979 and 1999, was 0.4%( annual incidence in USA was estimated as 600 000 cases) •342 000 inhabitants in Brittany, France, the incidences of VTE and PE were 18.3 and 6.0/10 000/year respectively. European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Predisposing factors for venous thromboembolism VTE is currently regarded as the result of the interaction between patient- related and setting -related risk factors. European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Additional risk markers.Clinical and routine laboratory tests European Heart Journal (2008) 29, 2276–2315 A recent survey performed in 358 hospitals across 32 countries shows that only 58,5 and 39,5% patients at risk of VTE due to medical or surgical causes, respectively, received adequate prophilaxis ( 1 ) Reports of a high risk of PE among obese people,smokers and patients affected by systemic hypertension or metabolic syndrome have renewed interest in the link between arterial thomboembolism and VTE( 2 ) ( 1 )Endorse Study-Lancet 2008;371:387-394 ( 2 )Lancet 2007;370:1773-1779 Natural Hystory The evidence suggests that DVT develops less frequently in general than in orthopaedic surgery The risk of VTE after surgery is highest during the first two weeks but remains elevated for 2-3 months Antithrombotic prophylaxis significantly reduces the risk of periopera tive VTE The longer the duration of antithrombotic prophylaxis,the lower the incidence of VTE Most patients with symptomatic DVT have proximal clots, and PE in 4050% of cases ( often asymptomatic ) PE occurs 3-7 days after the onset of DVT, and may be fatal within 1 h after the onset of symptoms in 10% of cases PE presents with shock or hypotension in 5-10% of cases Natural Hystory -In up to 50% of cases without shock but with lab. signs of RVD and /or injury indicates a poorer prognosis -After PE , complete risolution of perfusion defects occurs in about two thirds of all patients -Most deaths ( > 90% ) seems to occur in untreated patients , because of unricognized PE -Fever than 10% of all deaths were thought to occur in treated patients -CTETH was found in 0,5-5 % of patients with treated PE -The frequency of VTE recurrence is higher in patients with idiopatic VTE -The risk of fatal PE is higher after a previous episode of isolate DVT -Without anticoagulation about 50% of patients with symptomatic prox. DVT or PE have a recurrence of thombosis within 3 months -In patients with previous VTE who have finished their course of at least 3 – 12 months of VKI the risk of fatal PE was 0,19-0,49 events/pat/year Pathophysiology • The consequences of acute PE are primarily haemodinamic and become apparent when > 30-50% of the pulmonary arterial bed is occluded by thromboemboli • Large e/o multiple emboli might abruptly increase vascular resistence to a level of afterload which cannot be matched by the right ventricle. • Sudden death may occur ,usually in the form of electromechanical dissociation • Alternatively , the patient presents with syncope and /or systemic hypotension, wich might progress to shock and death due to acute RV failure • Rightward bulging of the interventricular septum may further compromise cardiac output as a result of diastolic left ventricle ( LV) disfunction • Decrease of aortic pressure may affect RV coronary perfusion and the function of RV • However, a non preconditioned , thin walled Rv is not expected to generate mea pulmonary pressures exceding 40 mm Hg • Secondary haemodinamic destabilization may occur , usually within 24 – 48 hour,as a result of recurrent emboly and /or deterioration of RV function. • This may be caused by early recurrences, which are common in undiagnosed or inadequately treated VTE • Alternatively , compensatory inotropic and chronotropic stimulation may not suffice to mantain RV function , with increased RV myocardial oxygen demand and decreased RV coronary perfusion gradient • Both elements contribute to RV ischaemia and dysfuncion, and may initiate a vicious circle leading to a fatal outcome • Pre-existing cardiovascular disease ……………… • Respiratory insufficience in PE is predominantly a consequence of haemodinamic disturbance • Several factors may contribute to hypoxia during a episode of PE: -Low cardiac output results in desaturation of mixed venous blood - Ventilation / perfusion mismatch - 1/3 right to left shunt trough a patent foramen ovale ( ipoxaemia , risk of paradoxycal embolization) ESC GuideLine 2008: Acute Pulmonary Embolism European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism European Heart Journal (2008) 29, 2276–2315 Severity of Pulmonary Embolism Severity of Pulmonary Embolism Severity of Pulmonary Embolism Risk-Adjusted Treatment Strategy European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Diagnosis: Clinical Presentation European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism D-dimer levels are elevated in plasma in the presence of an acute clot because of simultaneous activation of coagulation and fibrinolysis. Hence, a normal D-dimer level renders acute PE or DVT unlikely, i.e. the negative predictive value (NPV) of D-dimer is high On the other hand, although D-dimer is very specific for fibrin, the specificity of fibrin for VTE is poor because fibrin is produced in a wide variety of conditions, such as cancer, inflammation, infection, necrosis, dissection of the aorta, and the positive predictive value (PPV) of D-dimer is low European Heart Journal (2008) 29, 2276–2315 A negative D-dimer result in higly sensitive assay safely excludes PE in patients with a low or moderate clinical probability, while a moderately sensitive assay excludes PE only in patients with a low clinical probability When using a recently introduced two level clinical probability assessment scheme , a negative D-dimer result excludes PE safely in PE – unlikely patients either by a higly sensitive or moderately sensitive assay In the emergency department , a negative ELISA D-dimer test can exlude PE without further testing in approximately 30% of patients ESC GuideLine 2008: Acute Pulmonary Embolism Compression ultrasonography and computed tomographic venography •Searching for a proximal DVT in patients with PE by CUS yields a positive result in around 20% of patients. •CUS can be used either as a backup procedure to reduce the overall false-negative rate when using single-detector CT •It can be performed to avoid CT when positive in patients with contraindications to contrast dye and/or irradiation. •Combining CT venography with CT angiography adds a significant amount of radiation and is not useful when using MDCT European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Ventilation–perfusion scintigraphy •A normal perfusion scan is very safe for excluding PE •Although less well validated, the combination of a nondiagnostic V/Q scan in a patient with a low clinical probability of PE is an acceptable criterion for excluding PE. •A high-probability ventilation–perfusion scan establishes the diagnosis of PE with a high degree of probability, but further tests may be considered in selected patients with a low clinical probability due to the lower PPV of a high-probability V/Q scan result in such patients. •In all other combinations of V/Q scan result and clinical probability, further tests should be performed. European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Computed tomography • A SDCT or MDCT showing a thrombus up to the segmental level can be taken as adequate evidence of PE in most instances, whereas the necessity to treat isolated subsegmental thrombi in a patient without a DVT is unclear. • In patients with a non-high clinical probability, a negative SDCT must be combined with negative CUS to safely exclude PE, whereas MDCT may be used as a stand-alone test. •Whether further testing is mandatory in the rare patients who have a negative MDCT despite a high clinical probability is not settled. European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Pulmonary angiography • Pulmonary angiography is a reliable but invasive test and is currently useful when the results of non-invasive imaging are equivocal. •Whenever angiography is performed, direct haemodynamic measurements should be performed. European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Echocardiography • In a patient with suspected PE who is in a critical condition, bedside echocardiography is particularly helpful in emergency management decisions. •In a patient with shock or hypotension, the absence of echocardiographic signs of RV overload or dysfunction practically excludes PE as a cause of haemodynamic compromise. •The main role of echocardiography in non-high-risk PE is further prognostic stratification to the intermediate or low-risk category. European Heart Journal (2008) 29, 2276–2315 Echocardiographic Parameters • Estimates from postmortem data suggests that 30-50% of PE are never diagnosed, and misdiagnosis is also common • This results in large part from signs and symptoms that frequently overlap with other cardiopulmonary disorders • Consequently , the initial diagnostic test obtained in patients with symptoms suggestive of PE is frequently something other than the modern gold standard of PE protocol CT scan • Many echocardiographic abnormalities in patients with PE has been described • Most lack sufficient sensibility and specificity as a stand alone test • However ,Echo , is easily obtained , safe, portable , frequently obtained prior the definitive diagnosi of PE . • Understanding the utility of Echo findings is critical because they may increase the clinician’s suspicion for PE RV and LV EDD and Area from apical four chamber view Mc Connell Sign ,from apical four chamber view “Free wall ipokinesis or akinesis coupled with normoor hyperkinesia of the RV apex” “ D “ – sign or systolic flattening or shifting of the interventricular septum as seen from the parasternal short axis view • Qualitative indices: Mc Connell Sign-” D “ sign • Quantitative Indices: - Pulmonary artery diameter - RV EED - LV EDD - Ratio RV EDD/ LV EDD - RV area - LV area - Rv / LV area ratio - PA AcT -TR velocity - “60/ 60 “ sign ESC GuideLine 2008: Acute Pulmonary Embolism European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Diagnostic strategies European Heart Journal (2008) 29, 2276–2315 ESC Guideline 2008: Acute Pulmonary Embolism Diagnostic strategies European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism European Heart Journal (2008) 29, 2276–2315 ESC Guideline 2008: Acute Pulmonary Embolism European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism European Heart Journal (2008) 29, 2276–2315 ESC Guideline 2008: Acute Pulmonary Embolism Treatment: Haemodynamic and respiratory support •Haemodynamic and respiratory support is necessary in patients with suspected or confirmed PE presenting with shock or hypotension. •Isoproterenol is an inotropic drug which also induces pulmonary vasodilatation, but these favourable effects are often outweighed by peripheral vasodilatation. •Norepinephrine appears to improve RV function via a direct positive inotropic effect while also improving RV coronary perfusion by peripheral vascular alpha receptor stimulation and the increase in systemic blood pressure. No clinical data are available on the effects of norepinephrine in PE, and its use should probably be limited to hypotensive patients •The use of dobutamine and/or dopamine can be considered for patients with PE, low cardiac index and normal blood pressure. European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Treatment: Haemodynamic and respiratory support •There are few data with respect to inhaled aerosolized prostacyclin in the treatment of pulmonary hypertension secondary to PE •Preliminary experimental data suggest that levosimendan may restore right ventricular–pulmonary arterial coupling in acute PE as a result of combined pulmonary vasodilation and increased RV contractility •There is increasing interest in the use of endothelin antagonists and phosphodiesterase-5 inhibitors in PE. In experimental studies, antagonism of endothelin receptors attenuated the severity of pulmonary hypertension caused by massive P •Sildenafil infusion also attenuated the increase in pulmonary artery pressure in experimental PE be taken to limit its adverse haemodynamic effects. •When mechanical ventilation is required, care should positive intrathoracic pressure induced by mechanical ventilation may reduce venous return and worsen RV failure in patients with massive PE. Therefore, positive end-expiratory pressure should be applied with caution. Low tidal volumes (approximately 6 ml/kg lean body weight) should be used in an attempt to keep the end-inspiratory plateau pressure below 30 cm H2O European Heart Journal (2008) 29, 2276–2315 Thrombolytic Agents and Regimens and Contraindications to Thrombolysis Konstantinides S. N Engl J Med 2008;359:2804-2813 ESC Guideline 2008: Acute Pulmonary Embolism Treatment: Surgical pulmonary embolectomy Treatment: Percutaneous catheter embolectomy and fragmentation Catheter embolectomy or fragmentation of proximal pulmonary arterial clots may be considered as an alternative to surgical treatment in high-risk PE patients When thrombolysis is absolutely contraindicated or has failed. European Heart Journal (2008) 29, 2276–2315 Anticoagulant Drugs for Initial Treatment of Pulmonary Embolism Konstantinides S. N Engl J Med 2008;359:2804-2813 ESC Guideline 2008: Acute Pulmonary Embolism Treatment: Initial anticoagulation European Heart Journal (2008) 29, 2276–2315 ESC Guideline 2008: Acute Pulmonary Embolism Treatment: Initial anticoagulation European Heart Journal (2008) 29, 2276–2315 ESC Guideline 2008: Acute Pulmonary Embolism Treatment: Therapeutic strategies European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Treatment: Long-term anticoagulation and secondary prophylaxis •The long-term anticoagulant treatment of patients with PE is aimed at preventing fatal and non-fatal recurrent VTE events. •VKAs are used in the vast majority of patients, while LMWH may be an effective and safe alternative to VKAs in cancer patients. •VKAs should be given at doses adjusted to maintain a target INR of 2.5 (range 2.0–3.0). •Most of the studies focusing on long-term anticoagulation for VTE included patients with DVT, and only one study specifically focused on patients with PE •However, the implications for treatment of proximal DVT or PE are very similar, the main difference being that recurrent episodes are about three times more likely to be PE after an initial PE than after an initial DVT European Heart Journal (2008) 29, 2276–2315 ESC Guideline 2008: Acute Pulmonary Embolism Treatment: Long-term anticoagulation and secondary prophylaxis European Heart Journal (2008) 29, 2276–2315 ESC GuideLine 2008: Acute Pulmonary Embolism Treatment: Venous filters •Interruption of the inferior vena cava as a method or preventing PE was first suggested by Trousseau in 1868. •Venous filters became available in the late 1960s and percutaneous deployment was made possible almost 30 years ago. •Filters are usually placed in the infrarenal portion of the inferior vena cava (IVC). •If thrombus is identified in the IVC below the renal veins, more superior placement may be indicated. •Permanent IVC filters may provide lifelong protection against PE; •However, they are associated with complications and late sequelae, including recurrent DVT episodes and development of the post-thrombotic syndrome. •Complications of permanent IVC filters are common, although they are infrequently fatal European Heart Journal (2008) 29, 2276–2315 Discussione del Caso Clinico • In un paziente con EP sospetta l’iter diagnostico dovrebbe comprendere la valutazione della probabilità basata su scores validati. • Se la probabilità è intermedia / bassa , un D-dimero basso esclude sostanzialmente la diagnosi, mentre un D-dimero aumentato impone l’esecuzione di una MDCT Contrast-Enhanced CT Angiograms Showing Acute Pulmonary Embolism Tapson V. N Engl J Med 2008;358:1037-1052 • Il nostro paziente ha una probabilità clinica Intermedia , un Ddimero positivo , emboli in rami delle aa polmonari • Deve iniziare immediatamente terapia anticoagulante ( EBPM / Fondaparinux) • MDCT mostra disfunzione del VDx : si tratta dunque di EP a rischio intermedio. • Si può considerare la terapia trombolitica che però in questo caso ha un ruolo incerto perche’ la troponina è negativa • Si inizia TAO al II° - III° giorno di ospedalizzazione ( per assicurarsi che la disfunzione del vdx non progredisca verso l’instabilità emodinamica ,che richiederebbe la trombolisi) • Si sospende l’eparina quando INR ( 2-3 ) si è stabilizzato per 2 giorni consecutivi Take home messages • PE is a common disease wich may lead to a life threatening right ventricular failure.Even an apparently mild episode of PE should be promptly diagnosed and treated to prevent early and potentially life threatening recurrences • Because of non specific clinical presentations PE should be always considere in the differential diagnosis of dyspnoea, chest pain , syncope and many other clinical symptoms and signs.Of note , 20-30% patients with PE have no predisposing factors • Only appropriately validated diagnostic strategies should be used to justify specific PE treatment as witholding anticoagulation despite clinical suspicion of acute PE • Diagnostic and management strategy should be chosen according to the severity of a ( suspected or confirmed) PE episode,understood as the level of risk of early PE – related death • Pat. with shock or hypotension are suspected to have “ High risk PE “ ( early mortality > 15%) and requires immediate diagnostic work –up to decide whether or not emergency thrombolysis and / or embolectomy is justified. MDTC or ECHO are most useful tools in such emergency • Remaining patients are suspected to have “Non –high –risk PE”.In this case diagnostic evaluation should be stratified according to the level of clinical probability of PE-It can be assessed with validated scores or by clinical judgement • Negative D-dimer result obtained with a high sensitive test can help to select patients with a low to intermediate clinical probability of PE in whom anticoagulation may be safely withold without further diagnostic evaluation • In all other patients more estensive algorithms should be followed,based on MDCT evaluation.In specific clinical conditions and in cases with discordant results of clinical evaluation and CT angiography, alternative validated diagnostic strategies/test should be used for therapeutic decision making • Unfractionated i.v. heparin should be used in pat. With “High – risk-PE, severe renal dysfunction or at high bleeding risk.In all other case s.c. LMWH or Fondaparinux are recommended as initial treatment and should be followed by long term oral anticoagulation • Thrombolysis or ( if contraindicated or failed) embolectomy is recommended in “ High –risk –PE” • “ Non – high- risk PE” may furher risk stratified.The presence of objective signs of RVD e/o myocardial injury identify “ Intermediate-risk PE” in wich thrombolysis is not routinely recommend but may be considered in selected patients • “Low risk PE” can be diagnosed if no signs of right ventricular dysfunction or myocardial injury can be detected.If free from precedent co-morbidities,such patients may be considered for early discharge and ambulatory treatment • Percutaneous interventions , such as thrombus fragmentation/aspiration and venous filter implantation may be considered in selected clinical situations • The duration of the long term oral anticoagulant therapy should be decided based on the presence and reversibility of factors predisposing to recurrent venous thromboembolic disease Major gaps in evidence Diagnosis • Whether negative MDCT angiography alone permits to whithold anticoagulation treatment despite high clinical probability of PE remains unclear • Diagnostic signifiance of sub-segmental pulmonary clots documented at MDCT angiography is unclear • The respective value of three levels versus –two levels stratification of clinical probability of PE remains unclear Prognostic assessment • The optimal cut- of values of ECHO, CT and Biomarckers – derived criteria of RV overload remains to be defined • The optimal cut- off levels of troponin and new biomarkers of myocardial injury remain to be defined • The prognostic signifiance of concomitant presence of signs of right ventricular dysfunction and myocardial injury needs to be defined Pharmacological therapy • Whether ( and how to identified ) a subgroup of patients with “ intermediate-risk PE “ would benefit more from thrombolytic threatment than heparin- lone therapy is unclear • The safely and efficacy of new generation of oral anticolagulant in initiak and long term treatment of PE needs to be defined Intervention The safety and efficacy of retrievable venous filters needs further assessment. The safety and efficacy of percutaneous intervention (fragm/ aspir) in acute PE needs further assessment