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The diagnosis and prognosis of venous thromboembolism : variations on a
theme
Gibson, N.S.
Publication date
2008
Link to publication
Citation for published version (APA):
Gibson, N. S. (2008). The diagnosis and prognosis of venous thromboembolism : variations
on a theme.
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Prognosticvalueofechocardiography
andspiralcomputedtomography
inpatientswithpulmonaryembolism
NADINES.GIBSON,MAAIKESÖHNE,HARRYR.BÜLLER
124
A
BSTRACT
Purposeofreview
The identification of patients with pulmonary embolism who are at risk for mortality or severe morbidity in the early observation period is important since these patients may benefit from more aggressive initial treatment such as thrombolysis or catheter removal of the thrombus. Right ventricular dysfunction hasbeensuggestedtohaveaprognosticvaluefortheoccurrenceoftheseadverse outcomes.
Thepurposeofthisreviewistodeterminetheprevalenceandprognosticvalueof 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 ventriculardysfunction.
Recentfindings
Sevenstudiesusingechocardiographywereincludedwithatotalof3468patients and six studies using spiral computed tomography with a total of 868 patients were identified. The prevalence of right ventricular dysfunction with echocardiographyinnormotensivepatientswasapproximately30to40%,witha positive predictive value for shortterm mortality of approximately 5%. These indices could not be calculated for normotensive patients in the studies using spiralcomputedtomography.
Summary
The studies using echocardiography show that there is an association between right ventricular dysfunction and prognosis of pulmonary embolism in normotensivepatients.Whetherthisisclinicallyusefulinguidingmoreaggressive therapy remains to be determined, however. Thus far, the results of the studies with spiral computed tomography are too preliminary to enable definite conclusionstobedrawnforthenormotensivepatientgroup.
125 C HAPTER 9
I
NTRODUCTION
Thecurrentconsensusontheuseofthrombolytictherapyinpatientswithpulmonary embolismistolimitthistreatmenttothosepresentingwithhemodynamicinstability1. Inthelargegroupofhemodynamicallystablepatients,thrombolytictherapyhasnot beenshowntoimproveoutcome2.Ithasbeendebated,however,thattheremaybeasubgroup with asymptomatic right ventricular dysfunction (RVD) whose members may benefit from thrombolytic agents, because RVD would be an indicator for a highermortalityandmorbidityinthisgroup,partlybecauseofpulmonaryembolism. SeveralstudieshavesuggestedthisassociationbetweenRVDandadverseoutcomes; however, the inclusion criteria, diagnostic techniques, and definition of RVD vary amongthedifferentstudies312.Classically,echocardiographywasusedtodetectRVD,
whereasspiralcomputedtomography(CT)hasrecentlyemergedasanotherimaging technique that may be useful to diagnose RVD. Echocardiography is not routinely performed in pulmonary embolism patients and is time consuming. Spiral CT is gradually becoming the first imaging technique in the diagnostic examination of patients with suspected pulmonary embolism and therefore it would be fast and simpleifthesamescancouldbeusedtodeterminethepresenceorabsenceofRVD. WesearchedandreviewedtheliteraturefortheprognosticvalueofRVDdiagnosed witheitherechocardiographyorspiralCTinpatientswithpulmonaryembolism13.
R
IGHTVENTRICULARDYSFUNCTIONONECHOCARDIOGRAPHY
Echocardiography is at present regarded as the gold standard in confirming or excluding RVD in patients with pulmonary embolism. We identified seven clinical outcomestudiesusingechocardiography.
The baseline characteristics of these studies showed that five studies included normotensiveaswellashypotensivepulmonaryembolismpatients,whereasseparate mortality data for normotensive patients were available in two studies6,12. Detailson
comorbidity were reported in three studies. The presence of both cardiac disease (congestive heart failure and ischemic heart disease) and chronic obstructive pulmonarydisease(COPD)variedbetween10%and14%,whereastheprevalenceof malignancyrangedfrom10to22%.Apreviousepisodeofvenousthromboembolism wasseenin16to52%ofpatients46,10.
126
Table 1. Details of the seven studies in patients with pulmonary embolism and right ventricular
dysfunction on echocardiogarphy.
Source Study-type Follow-up
No. of patients with confirmed PE and available echocardio- graphy (total no. of pat)
Goldhaber et al, 1993 RCT in-hospital 101 (101)
Ribeiro et al, 1997 PCS * one year 126 (157)
Kasper et al, 1997 PCS one year 164 (317)
Goldhaber et al, 1999 registry 3 months 1135 (2454)
Grifoni et al, 2000 PCS in-hospital 207 (209)
Jerjes-Sanchez et al, 2001 PCS > one year 40 (40)
Sukhija et al, 2005 retrospective in-hospital 190 (190)
RCT, randomized controlled trial
* PCS, prospective cohort study
‡ Percentage estimated from the Kaplan-Meier curve
ThecriteriaforRVDvariedinthesevenstudiesinpulmonaryembolismpatients.The maincriteriausedbyalmostallstudiesforthedefinitionofRVDwerethepresenceof ventricularwallmotionabnormalitiesanddilatationoftherightventricularcavity.
In the majority of the studies, qualitative right ventricular wall hypokinesis was considered to be a sign of RVD, classified as mildly, moderately or severely hypokinetic47,10. The quantitative right ventricular/left ventricular enddiastolic
diameterratiowasalsofrequentlyused,withacutoffvalueofthisratioabove1.068,12.
Kasperetal.alsousedthisratiotodefineRVDbut,inaddition,definedRVDiftwoof the following criteria were present: tricuspid regurgitation, dilatation of the right pulmonary artery, right ventricular wall thickness greater than 5 mm, and loss of inspiratory collapse of the inferior vena cava8. Sukhija et al. used, in addition to the
abovementionedcriteriaofKasperetal.,thepresenceofparadoxicseptalmotion8,12.
Table1detailsthestudydesignsaswellastheprevalencesandoutcomesintheseven studies.TheprevalencesofRVDattimeofdiagnosisofpulmonaryembolismvaried
127 C HAPTER 9
between 27% and 56%, except for the study of JerjesSanchez et al., in which a prevalenceof70%wasfound7.Thelowestprevalences,between27%and40%,were
observed in study populations with only hemodynamically stable patients5,6,12,
whereasthehighestprevalenceof70%wasfoundin40patients,ofwhomalmosthalf wereincardiogenicshock7.
With respect to outcome, it is important to realize that the duration of longterm followup differed, varying from 3 months to more than 1 year. Three studies reportedonlyontheinhospitalperiod(i.e.approximately14days)4,6,12.Adescription
of completeness of followup was available in two studies, with values of 83% and 98%,respectively5,7.
Totalshorttermmortality,definedasmortalityduringtheinhospitalperiod,varied between 2% and 14%, whereas in patients with RVD these percentages varied between4%and33%.Theabsolutedifferencesintotalshorttermmortalitywithinthe studiesbetweenpatientswithandwithoutRVDrangedfrom4%to28%. Hemodynamic status at presentation Presence of right ventricular dysfunction n (%)
Total short term mortality n (%)
Total short term mortality in right ventricular dys-function patients n (%) Stable 46 (46) 2 (2) 2 (4) not reported 70 (56) 10 (8) 10 (14) not reported 72 (44) 29 (9) 16 (18) 2182 stable 454 (40) 280 (11) (16)‡ 162 normotensive 19 hypotensive 28 shock 110 (53) 17 (8) 14 (13) 24 normotensive 16 shock 28 (70) 5 (13) 5 (18) 172 normotensive 18 hypotensive 64 (34) normotensive: 46 (27) 27 (14) 21 (33) normotensive: 19 (41)
128
The shortterm pulmonary embolismrelated mortality varied from 2 to 10%, with absolutedifferencesbetweenpatientswithandwithoutRVDof4%to14%48,10.
Long term total mortality, defined as a minimum followup time of three months, rangedfrom9to17%.InthetwostudiesthatspecifiedthisforRVDpatients,thelong term total mortality was 18% and 21%, respectively8,10. The longterm pulmonary
embolismrelated mortality for the RVD patients was 13% in both studies, and this was0%and1%forthepatientswithoutRVD.
In the studies including both normotensive and hypotensive patients, the positive predictive values of RVD for the shortterm total mortality varied between 13% and 33%68,10.Forpulmonaryembolismrelatedshorttermmortality,thesevaluesdiffered
between 12% and 18%68,10,12. For patients whose condition was hemodynamically
stable,thepositivepredictivevaluesof RVDfor pulmonaryembolismrelatedshort term mortality could be calculated in two studies including 263 normotensive patients4,6. These were 4%and 5%, respectively. These percentages are in contrast to
thepositivepredictivevalueof41%fortotalshorttermmortalityinanotherstudyof 172normotensivepatients12.
R
IGHTVENTRICULARDYSFUNCTIONONSPIRALCT
Sixstudieswereidentifiedthatevaluatedtherelationbetweenpulmonaryembolism relatedRVDonspiralCTandoutcome(Table2).In contrast to the studies using echocardiography, most of which had a prospective design,allspiralCTstudieswereretrospective.Thefollowuptimeswerereportedin fourstudiesandvariedfromtheinhospitalperiodto3months3,9,11,14.
With respect to hemodynamic status and comorbidity there was heterogeneity betweenthedifferentstudypopulations.Fourstudiesincludedamixtureofpatients withnormalanddecreasedbloodpressure,whereasthehemodynamicstatewasnot mentioned in the two remaining studies3,15. Comorbid conditions such as cardiac
diseaseandCOPDwerereportedinthreestudies,andprevalencesvariedbetween6% and11%3,9,11.Theprevalenceofmalignancyinthesestudieswashigh:32to54%.
129 C HAPTER 9 criterionforRVD,therightventricular/leftventriculardiameterratio,wasusedinall studies;however,thecutoffvalueforthisdiameterratiodifferedfromaratiogreater than0.9toaratiogreaterthan1.516.Inonestudy,nocutoffvalueforthisratiowas
used, but the mean ratio was given for patients with severe pulmonary embolism, those with non severe pulmonary embolism, and those without pulmonary embolism14.
With singleslice spiral CT, this ratio can be measured in the usual axial transverse view3,1416. Multislice spiral CT can make a reconstruction of the fourchamber view
perpendicularonthelongaxisofthehearttomeasurethisratio,whichgivesamore accuratemeasurement3,9,11.
Several other measurements have been used to describe RVD, including interventricularseptalbowing,themaximumdiameteroftherightandleftventricle, thediameterofthecentralpulmonaryarteryandsuperiorvenacava,rightventricular wallthickness,andrefluxintotheinferiorvenacava14.
As expected, the prevalence of RVD on spiral CT varied with these different definitions. In studies that used a higher cutoff value for right ventricular/left ventricularratio(i.e.between1.0and1.5),theprevalenceofRVDwaslower(2225%) thaninstudiesthatusedaratioof0.9toconfirmthepresenceofRVD(6471%)(Table 2)3,15,16.InthestudyofCollombetal.,noprevalenceforthisratiowasgiven,butthe
medianrightventricular/leftventricularratiowassignificantlyhigherinthepatients with severe pulmonary embolism and non severe pulmonary embolism than in the patientswithoutpulmonaryembolism(1.63and1.09comparedwith0.99,P<0.01)14.
Inthisstudy,theprevalenceofinterventricularseptumdisplacementasamarkerof RVD was prevalent in 15% of the patients with severe pulmonary embolism but in none of the patients with non severe pulmonary embolism or those without pulmonaryembolism.
ThreestudiesevaluatedtherelationbetweenRVDandoutcomeandshoweddifferent results3,9,11.ThestudybySchoepfetal.included431patientsandreportedatotal30
day mortality rate of 13% and a mortality rate of 16% in patients with RVD11. The
positivepredictivevalueofrightventricularenlargementonspiralCTfortheoverall mortalitywithin30daysinthisstudywastherefore16%.
130
Table 2. Details of the six studies in patients with pulmonary embolism and right ventricular
dysfunction on spiral computed tomography.
Source Study-type Follow-up
No. of patients with confirmed PE and available spiral CT (total no. of patients) Reid and Murchison,
1998
retrospective
no follow-up 28 (79)
Contractor et al, 2002 retrospective no follow-up 41 (41)
Collomb et al, 2003 retrospective 3 months 50 (81)
Araoz et al, 2003 retrospective in-hospital 173 (173)
Quiroz et al, 2004 retrospective 30 days 63 (63)
Schoepf et al, 2004 retrospective 30 days 431 (431)
•
SBP, systolic bloodpressure
* RVD defined as interventricular septum convex to left ventricle
RVD prevalence if measured in axial view RVD prevalence if measured in 4 chamber view
O NDA, no data available
In the study by Quiroz et al., which included only 63 patients, the outcome measurement included not only death within 30 days but also the escalation of treatment, which was defined as cardiopulmonary resuscitation, mechanical ventilation, administration of catecholamines, rescue thrombolysis, or surgical embolectomy9. In that study population, the total mortality was 22%, without a
breakdownforthosewithorwithoutRVD.ThepositivepredictivevaluesofRVDfor alladverseoutcomeswere38%and49%fortheaxialCTviewandthefourchamber CTview,respectively9.
ThethirdstudytoreportonoutcomeinrelationtoRVDwasthestudyofAraozetal., in which the total mortality in 173 patients was 5%3. No relation could be found
131 C HAPTER 9 Hemodynamic status RVD n (%) Total mortality n (%) Total mortality in RVD n (%) 77 normotensive 2 SBP• <100 mmHg 7 (25) 0 (0) NDA NDAO 9 (22) NDA 0 (0) 61 normotensive 20 mean SBP of 82 mmHg 3 (15)* 4 (8) NDA NDA 39 (23) 8 (5) NDA 50 normotensive 13 SBP < 90 mmHg 45 (71) 39 (62) 14 (22) not specified
38 systemic arterial hypotension 276 (64) 55 (13) 43 (16)
R
IGHTVENTRICULARDYSFUNCTIONONECHOCARDIOGRAPHY
ANDSPIRALCT
Three studies used echocardiography as well as spiral CT to measure RVD in the same population. Two of these studies allowed a direct comparison of the two imaging techniques9,15. Contractor et al. studied approximately 20 patients and
reported a prevalence of RVD of 22% on spiral CT, compared with 30% on echocardiography15. Quiroz et al. reported in a series of 63 patients a prevalence of
RVDonspiralCTintheaxialviewof71%,inthereconstructedfourchamberviewof 81%,whereasechocardiographyshowedaprevalenceof71%9.
P
REDICTIVEVALUEOFRIGHTVENTRICULARDYSFUNCTIONIN
PATIENTSWITHACUTEPULMONARYEMBOLISM
ThestudiesinthisoverviewprovideevidencethatRVDinpatientswithpulmonary embolism, detected by either echocardiography or spiral CT, has a significant prevalence and is associated with early death or adverse outcome in these patients, particularlyinthefirstweeks.Thestudypopulationswerenotcomparable,avariety ofcriteriawereusedtodefineRVD,andoutcomemeasuresweredifferent.Therefore the data of the studies cannot be pooled, and no overall estimate of prevalence and
132
positivepredictivevaluecanbegiven.
The main distinction is between those studies that included both hemodynamically stable and unstable patients and those that included only hemodynamically stable patients. This latter population is the actual group of interest in predicting adverse events during followup, because the discussion about the use of more aggressive therapyfocusesonthesepatients.
The methodological quality of the studies using echocardiography was in general betterthanthatofthestudiesusingspiralCT.Nearlyallwereprospectiveandhadan adequatefollowup.Theyincludedatotalof3468patients.TheprevalenceofRVDin thesepatientswasapproximately30to40%4,5,12. ThedesignsofthestudiesusingspiralCTwereallretrospective,andatotalofonly 868patientswereincluded.ThesestudiesdidnotallowforacalculationoftheRVD prevalenceinnormotensivepatients.
The positive predictive values of RVD for shortterm mortality varied widely in all studies. For hemodynamically stable patients, data from two echocardiography studies of 263 patients were available. The positive predictive value was approximately 5%4,6. The studies using spiral CT lacked data for this patient group,
and the positive predictive value of RVD defined by this technique for mortality in normotensivepatientsthereforeremainsunknown.
Echocardiographyisnotroutinelyperformedinpatientswithpulmonaryembolism; it is an operator dependent modality and is time consuming. Patient characteristics suchasobesityandrespiratorydistressmaynotpermitanoptimalstudy.Moreover, spiral CT is becoming the main diagnostic imaging technique, and its use for diagnosis as well as prognosis would result in a fast and easy diagnostic and prognostic conclusion, allowing for an immediate and patientadjusted treatment decision. Thus far, two small studies have compared both techniques and showed similarprevalencesofRVDonechocardiographyorspiralCT.
133 C HAPTER 9
C
ONCLUSION
Insummary,itistooearlytodrawconclusionsontheusefulnessofRVDdetectedby spiral CT for the prognosis in hemodynamically stable patients with pulmonary embolism. Studies with echocardiography do show the presence of RVD in these patientsanditsassociationwithoutcome;however,moreresearchisneededtoguide managementdecisionsinthefuture.
Irrespective of the use of echocardiography or spiral CT, the main point for future research is the determination of a uniform set of criteria to define RVD. Moreover, experts should establish criteria for the outcome measures that are consistent and plausiblyattributabletopulmonaryembolism.
134
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