2014ESC急性肺栓塞诊断和管理指南(英文版)(7)

Some experts believe that patients with incidental(unsuspected) PE on CT should be treated,144especially if they have cancer and a proximal clot,but solid evidence in support of this recommendation is lacking.The value and cost-effectiveness of CUS in suspected PE should be further clari?ed.

Finally,‘triple rule-out’(for coronary artery disease,PE and aortic dissection)CT angiography for patients presenting with non-traumatic chest pain appears to be accurate for the detection of cor-onary artery disease.209However,the bene?ts vs.risks(including increased radiation and contrast exposure)of such a diagnostic ap-proach need thorough evaluation,given the low(,1%)prevalence of PE and aortic dissection in the studies published thus far.

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short-term prognosis.For example,in the International Cooperative Pulmonary Embolism Registry(ICOPER),age.70years,systolic BP ,90mm Hg,respiratory rate.20breaths/min,cancer,chronic heart failure and chronic obstructive pulmonary disease(COPD), were all identi?ed as prognostic factors.48In the Registro Informati-zado de la Enfermedad Thomboembolica venosa(RIETE)study,im-mobilization for neurological disease,age.75years,and cancer were independently associated with an increased risk of death within the?rst three months after acute VTE.47The diagnosis of con-comitant DVT has also been reported to be an independent predict-or of death within the?rst three months following diagnosis.210 Various prediction rules based on clinical parameters have been shown to be helpful in the prognostic assessment of patients with acute PE.Of those,the pulmonary embolism severity index(PESI; Table7)is the most extensively validated score to date.211–214In one study,215the PESI performed better than the older Geneva prog-nostic score216for identi?cation of patients with an adverse30-day outcome.The principal strength of the PESI lies in the reliable identi-?cation of patients at low risk for30-day mortality(PESI Class I and II). One randomized trial employed a low PESI as the inclusion criterion for home treatment of acute PE.217

Owing to the complexity of the original PESI,which includes11dif-ferently weighted variables,a simpli?ed version known as sPESI (Table7)has been developed and validated.218,219In patients with PE,the sPESI was reported to quantify their30-day prognosis better than the shock index(de?ned as heart rate pided by systolic BP),220and a simpli?ed PESI of0was at least as accurate for identi?-cation of low-risk patients as the imaging parameters and laboratory biomarkers proposed by the previous ESC Guidelines.221Combin-ation of the sPESI with troponin testing provided additional prognos-tic information,222especially for identi?cation of low-risk patients.76 4.2Imaging of the right ventricle by echocardiography or computed tomographic angiography

Echocardiographic?ndings indicating RV dysfunction have been reported in≥25%of patients with PE.223They have been identi?ed as independent predictors of an adverse outcome,224but are heterogeneous and have proven dif?cult to standardize.225Still,in haemodynamically stable,normotensive patients with PE,echocardio-graphic assessment of the morphologyand function ofthe RV may help in prognostic strati?cation.

As already mentioned in the previous section on the diagnosis of PE,echocardiographic?ndings used to risk stratify patients with PE include RV dilation,an increased RV–LV diameter ratio,hypokinesia of the free RV wall,increased velocity of the jet of tricuspid regurgi-tation,decreased tricuspid annulus plane systolic excursion,or com-binations of the above.Meta-analyses have shown that RV dysfunction detected by echocardiography is associated with an ele-vated risk of short-term mortality in patients without haemodynamic instability,but its overall positive predictive value is low (Table8).226,227In addition to RV dysfunction,echocardiography can also identify right-to-left shunt through a patent foramen ovale and the presence of right heart thrombi,both of which are associated with increased mortality in patients with acute PE.80,184

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Four-chamber views of the heart by CT angiography may detect RV enlargement(end-diastolic diameter,compared with that of the left ventricle)as an indicator of RV dysfunction.Following a number of early retrospective studies,227the prognostic value of an enlarged RV on CT angiography was con?rmed by a prospective mul-ticentre cohort study of457patients(Table8).228In-hospital death or clinical deterioration occurred in44patients with-and in8patients without RV dysfunction on CT(14.5%vs.5.2%;P,0.004).Right ven-tricular dysfunction was an independent predictor for an adverse in-hospital outcome,both in the overall population(HR3.5;95% CI1.6–7.7;P?0.002)and in haemodynamically stable patients (HR3.8;95%CI1.3–10.9;P?0.007).Additional recent publications have con?rmed these?ndings.229,230

4.3Laboratory tests and biomarkers

4.3.1Markers of right ventricular dysfunction

Right ventricular pressure overload is associated with increased myo-cardial stretch,which leads to the release of brain natriuretic peptide (BNP)or N-terminal(NT)-proBNP.The plasma levels of natriuretic peptides re?ect the severity of haemodynamic compromise and (presumably)RV dysfunction in acute PE.231A meta-analysis found that51%of1132unselected patients with acute PE had elevated BNP or NT-proBNP concentrations on admission.These patients had a10%risk of early death(95%CI8.0–13)and a23%(95%CI 20–26)risk of an adverse clinical outcome.232

In normotensive patients with PE,the positive predictive value of elevated BNP or NT-proBNP concentrations for early mortality is low.233In a prospective,multicentre cohort study that included 688patients,NT-proBNP plasma concentrations of600pg/mL were identi?ed as the optimal cut-off value for the identi?cation of elevated risk(Table8).234On the other hand,low levels of BNP or NT-proBNP can identify patients with a favourable short-term clinic-al outcome based on their high negative predictive value.226,232,235,236 Haemodynamically stable patients with low NT-proBNP levels may be candidates for early discharge and outpatient treatment.237

4.3.2Markers of myocardial injury

Transmural RV infarction despite patent coronary arteries has been found atautopsyofpatientswhodied ofmassivePE.238Elevatedplasmatropo-nin concentrations on admission have been reported in connection with PE and were associated with worse prognosis.A meta-analysis covering a total of1985patients showed elevated cardiac troponin I or-T concentrations in approximately50%of the patients with acute PE(Table8).239Elevated troponin concentrations were associated with high mortality both in unselected patients[odds ratio(OR)9.44; 95%CI 4.14–21.49]and in haemodynamically stable patients [OR5.90;95%CI2.68–12.95],and the results were consistent for troponin I or-T;however,other reports have suggested a limited prog-nostic value of elevated troponins in normotensive patients.240

The reported positive predictive value of troponin elevation for PE-related early mortality ranges from12–44%,while the negative

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predictive value is high,irrespective of the assays and cut-off values used.Recently developed high-sensitivity assays have improved the prognostic performance of this biomarker,particularly with regard to the exclusion of patients with an adverse short-term outcome.241For example,in a prospective,multicentre cohort of 526normotensive patients with acute PE,troponin T concentrations

,14pg/mL,measured by a high-sensitivity assay,had a negative pre-dictive value of 98%with regard to a complicated clinical course,which was similar to that of the sPESI.76Heart-type fatty acid-binding protein (H-FABP),an early marker of myocardial injury,was also found to possess prognostic value in acute PE.242,243In normotensive patients,circulating H-FABP levels ≥6ng/mL had a positive predictive value of 28%and a negative pre-dictive value of 99%for an adverse 30-day outcome (Table 8).244A simple score,based on the presence of tachycardia,syncope,and a positive bedside test for H-FABP,provided prognostic information similar to that of RV dysfunction on echocardiography.245,2464.3.3Other (non-cardiac)laboratory biomarkers Elevated serum creatinine levels and a decreased (calculated)glom-erular ?ltration rate are related to 30-day all-cause mortality in acute PE.247Elevated neutrophil gelatinase-associated lipocalin (NGAL)and cystatin C,both indicating acute kidney injury,have also been found to be of prognostic value.248Elevated D-dimer ESC Guidelines Page 18of 48 at Fujian University of Traditional Chinese Medicine on August 30, 2014e43f5da204a1b0717ed5dd2a/Downloaded from

concentrations were associated with increased short-term mortality in some studies,249,250while levels ,1500ng/mL had a negative pre-dictive value of 99%for excluding three-month all-cause mortality.2514.4Combined modalities and scores In patients with acute PE who appear haemodynamically stable at diagnosis,no inpidual clinical,imaging,or laboratory ?nding has been shown to predict risk of an adverse in-hospital outcome that could be considered high enough to justify primary reperfusion.As a result,various combinations of clinical ?ndings with imaging and laboratory tests have been proposed and tested in registries and cohort studies in an attempt to improve risk strati?ca-tion.222,246,254–259The clinical relevance of most of these modalities and scores,particularly with regard to the therapeutic implications,remains to be determined;however,the combination of RV dysfunc-tion on the echocardiogram (or CT angiogram)with a positive cardiac troponin test 256,260was used as an inclusion criterion in a recently published randomized thrombolysis trial,261which enrolled 1006normotensive patients with acute PE.Patients treated with standard anticoagulation had a 5.6%incidence of death or haemodynamic decompensation within the ?rst 7days following randomization.2534.5Prognostic assessment strategy For prediction of early (in-hospital or 30-day)outcome in patients with acute PE,both the PE-related risk and the patient’s clinical status and comorbidities should be taken into consideration.The def-inition for level of clinical risk is shown in Table 9.The risk-adjusted therapeutic strategies and algorithms recommended on the basis of this classi?cation are discussed in the following section and summar-ized in Figure 5.At the stage of clinical suspicion of PE,haemodynamically unstable patients with shock or hypotension should immediately be identi?ed as high-risk patients (Figure 2).They require an emergency diagnostic

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