- Email: [email protected]
Comparison of Doppler Echocardiography With Thermodilution for Assessing Cardiac Output in Advanced Congestive Heart Failure
T development of QT interval dispersion in chronic heart disease may have a different mechanism. Prolongation of action potential duration has been reported in ventricular hypertrophy and chronic congestive heart failure.19’20Prolongation of action potential duration could be due to altered function of some of the same depolarizing currents activated in acute ischemia.19,20Thus, in acute ischemia, QT interval dispersion is probably secondary to regional shortening of action potential durations, whereas in chronic heart disease, QT interval dispersion may be secondary to regional prolongation of the action potential durations. In the setting of acute myocardiai infarction, the interplay between ischemic living tissue and relatively depolarized dying tissue would create a complex transition period affecting QTc interval dispersion. One could hypothesize that very early in myocardial infarction, increases in QTc intervai dispersion would be primarily due to local shortening of the action potential. However, within a few hours, prolongation of the QT intervai could become the dominant feature governing QTc intervai dispersion, more like chronic heart disease. Anaiysis of the QT intervai data with regard to the minimum and maximum QT intervais obtained from our patient groups supports this hypothesis. The minimum QT intervai for patients who had ventricular fibrillation in the ‘“ setting of acute myocardiai infarction was significantly less than in those who did not experience ventricular fibrillation. This study suggests that QT intervai dispersion may predict the risk for ventricular fibrillation early in the course of acute myocardial infarction.
acute transmurrdmyocardialinfarction in human beings. Am J Cardiol h 1981;48:1023–1028. 2. MirvisDM.Spatialvariationof QT intervalsin normrdpersonsandpatients withacutemyucardialinfarction.JAm Coil Cardiol 1985;5:625–631. 3. Day CP, McCombJM, CampbellRWF. QT dispersion:an indicationof arrhythmiarisk in patientswith long QT intervaJs.Br Hear’fJ 1990;63:342– 344. 4. HiiJTY,WyseDG,GillisAM,DuffHJ, SolyloMA,MitchellLB.Prccordial QT”interval dispersion aa a marker of torsade de pointes. Circulation 1992;86:1376-1382. 5. LepeschkinE, SurawiczB. The measurementof the Q-T intervalof the electrccardiograrn. Circulation1958;17:378–388. 6. MurmyA,McLaughlinNB,BourkeJP,DoigJC,FomissSS,CampbellRWF. Errorsin manualmeasurementof QT interwds.Br Heart J 1994;71:386–390. Heart 7. BazettHC. An analysisof the time-relationsof electrucardiograma. 1920;7:353–370. 8. Pye M, Quirm AC,CobbeSM.QTintervafdispersion:a non-invasivemarker
of susceptibilitytu arrhythmiain patientswith sustainedverrtrictdararrhytfrmias?Br Heart J 1994;71:511-514. 9. Barr CS, NassA, FreemanM, Lang CC, StrutherzAD. QT dispersionand suddenunexpecteddeathin chronicbeartfailure.Z.ancet1994;343:327-329. 10. Day CP, JamesOFW, ButJerTJ, CampbellRWP. QT prolongationand suddendeathin patientswith afcoholicliver disease.Lmcet 1993;341:1423– 1428. 11. Buja G, MiorelliM, TrmiN P, MelaciniP, Nava A. Comparisonof QT dispersionin hypertmphiccardiomyopathybetweenpatientswith and without verrtricuJararrhythmiasand suddendeath.AmJ Cardiol 1993;72:973–976. 12. KautznerJ, Yi G, CaromJ, MalikM. Shortand long termreproducibility of QT, QTc, and QT dispersionmeasurementin healthy subjects. PACE 1994;17:928-937. 13. CowanJC, YusoffK, MooreM, AmosPA, GoldAE, BorrrkeJP, TansuphaswadikulS, CampbellRWF. Importanceof lead selectionin QT intervaf measurement.AmJ CardioZ 1988;61:83–87. 14. StattersD], MalikM, WardDE, CamrnAJ. QT Dispersion:Problemsof methodology aad clinical significance. J Cardiovascular Electrophysiol 1994;5:672–685. S, BourkeJP, MurrayA, Camp15. Cowrm JC, HiJtonCJ, Tansuphaawadikul
bell RWF. Sequenceof epicmdialrepularizatiouand configurationof OreT wave.Br Heart J 1988;60:424-433. 16. Yan GX, YamadaKA, KfeberAG, McHowatJ, Corr PB. Dissociation hehveencellularK’ loss,reductioninrepalarizationti me, andtissueATPlevels duringmyocardialhypoxiaand ischernia.Circ Res 1993;72;3:560-570. 17.PdoriSG,NapolitanoC,DiehlL, SchwartzP. DispersionoftheQTinterval. A markerof therapeuticefficacyin the idiupatic long QT syndrome.Circulation 1994;89:1681-1689. 18. KleimarrRB, HeuserSR. Outwardcurrentsin nnrmaland hypertruphied felineventricularmyocyt&.AmJPhysiol 1989;256:H1450–H1461. 19.FurukawaT, MyerburgRJ, FurukawaN, KirmrraS, BaasettAL.Metabulic inhibitionof ~~ and 1~differ%in feline left ventricularhypertrophy.Am J Physiol 1994;266:H1121-H1131. DJ, NabarrerM, GordmarurE. Alterationsof K+currentsin 20. Beuckelmsnm
1. CincaJ, FiguerasJ, TenorioL, Vane V, TrwrchsJ, SeguraR, F&s J. Time isolatedhumanventricularmyocytesfrompatientswithterminalheartfailure. cand rate dependenceof Q-T intervalchangesduringnoncomplicated Circ Res 1993;73:379–385.
EchocardiogruphyWith Thermodiktien for AssessingCardiacOutput in Advanced Congestive Heart Failure Comparison
of Ooppk
Andrea Gola, MD, Massimo Pozzoli, MD, Soccorso Capomolla, MD, Egidio Traversi, MD, Maurizio Sanarico, MS, Franco Cobelli, MD, and Iwigi Tavazzi, MD
n patients with chronic congestive “heart failure the quantification of cardiac ou~ut (CO) Iis (CHF) ‘m essentiai’part of the hemodynamic t%duation From the Salvatore Mau eri Foundation—institute of Research and Care, Rehabilitation Me 3 Ical Center, Mantescano, Pavia, Italy. Andrea Gala is recipient of a grant from the School of Cardiology, Departmentof InternalMedicine, Clinica Medica 1, University of Pavia, Pavia, Italy. Dr. Pozzoli’s address is: Salvatare Maugeri Foundation, Rehabilitation Medical Center, Depatiment of Cardiology, 27040 Montescano, Pavia, Italy. Manuscript received November 29, 1995; revised manuscriptreceivedand acceptedApril 4, 1996.
~
01996 by ExcerptaMedic., All rights reserved.
Inc.
that carries important therapeutic and prognostic implications. From among a variety of methods developed over the years to measure CO, the Fick oxygen method is probably the most accurate and is considered the standard reference technique.l This technique, however, requires right-sided heart catheterization and expired gas measurements, and cannot give instantaneous results. The thermodiluticm method, ~ application of the indicator dilution principle (in which the indicator is cold saiine), is the most widely used invasive method because it is easy 0002-9149/96/$15.00 Pll SOO02-9149(96]O040&7
to perform and allows instantaneous determination of CO-2,3It has been observed, however, that ther52 * 8 Age (yrs] modilution maybe inaccurate when low output states 24/49 Etiology (ixhemic/nonischemic) or tricuspid regurgitation, frequent occurrences in 33 [45%) New York Heart Association functional class chronic CHF, are present.4.5More recent studies have III-IV (patients) challenged these results, showing that thermodilu106 * 18 Systolic blaad pressure (mm Hg) 79 ~ 16 tion may be more accurate than previously Heart rate [beats/rein) 15 (20%) Atrial fibrillation (patients] claimed.b-8 To assess CO noninvasively, various 26 ~ 10 Left ventricular election fraction (%) Doppler echocardiographic methods have been pro34 (46%) Tricuspid regurgitation grade III-IV [patients) posed.9- 15From ~ong these, the left ventricular 36 (49%) Mitral regurgitation grade 111.IV[patients) outflow tract method has proved to be the most ac19 i 11 Pulmonary artsrry wedge pressure (mm Hg) 7*7 Right arial pressure (mm Hg) curate and reproducible, provided that no aortic re3.4 * 1.5 Cardiac output—Fick (L/rein] gurgitation is present. Despite this, its application for evaluating patients with CHF is fiir from being widespread, and a review of studies referenced in MedLine between 1994 and 1995, using the search terms Doppler echocardiography and cardiac outpw, revealed that a Doppler method for measuring CO was 8r used in only 38 clinical studies, . .’ of which only 6 concerned pa,’ 7 tients with CHF. ,“ o #.’ Accordingly,we directly coma o , ●’ 6 pared thermodilutionand Doppler ./ ,0 echocardiographic methods with ✌ ● ~, , ● the Fick oxygen method in patients with advanced CHF to ‘4 verify the agreement of thermo0 dilution with Fick’s method in 9 CO measurement particularly when low CO and/or tricuspid 6 ~, regurgitation is present, and esr 8 0.S1 tablish whether the Doppler ~wo.w method may represent ,avalid alCOFICK= 0.61+0.S7”COTH .. ternative to invasive techniques ~ L“” for measuring CO in these pa01234667 tients. 00 Fkk (I/miss) *. We studied 73 consecutive 4 patients (63 men and 10 women; t b mean age 52 f 8 years) with chronic advanced CHF owing to either ischemic (24 patients) or nonischemic (49 patients) dilated cardiomyopathy who were admitted to our heart failure unit and evaluated with a view to heart transplantation. Dilated cardiomyopathy was defined by i! the 2-dimensional echocardiou-z o ● Tstaus@d 0 graphic demonstration of a di4 lated left ventricle (left ventricI o NoTrksssspid ular end diastolic volume >78 ml/m2 of body surface area) with (COFkk + COTtsermastilutkn)F2 (lhnin) a left ventricular ejection fraction <3590. Patiedts with intracardiac . Mwe6n simuhseoustkssadiiutianandFickmeaswements FIGURE 1.a, Camdahan shunts, aortic valvular disease, d cardiac output(CO)Q~: :$s @osssd ciKM d {~ c+ ~wid and technically inadequate echorawn as a did Iisseand thelineof Asstiiyis WW9*. * &shed.6, Blanda3 Ahnsanplot camping Fickandthermadibtbrs mssasuremds of cardiograms were excluded. The rements, reparkdantheyssxk,arefsbtted dikmncesbetweenpairedmeasu CO.Thsr general characteristics of. the betwaenM6asssrsnsents i3 values (x axis).h meandi%renca against tlmir bycon- study group are summarized in nearlyzero~==blfine). b and2 = ofdikremss areirsdicakd Table I. All patients, who were TAME
I Principal
Characteristics
of the 73
Patients
Studied
I
1~
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BRIEF REPORTS
709
from the pulmonary artery and an arterial sample from the radial ar. tery. Their oxygen contents were 7 .“ measured using an ABL 500 ,# a .’ blood gas analyzer (Emdrupue, s ,0” /i Copenhagen, Denmark). CO was then calculated accordingly to the Fick formula. CO was considered to be low when <3.5 L/ min. The short-term variabilities, assessed in 20 CHF patients, of Q oxygen consumption at rest, arteriovenous oxygen difference, and Fick CO were 5Y0,7.8?40,and -0.s1 1 5.7%, respectively. co FCK=O.16+I,oi ‘co w The thermodilution method 1 o 1’was simultaneously applied to 01 284 S678 measure CO. Ten millilitres of iced saline solution (0°) were injected into the right atrium through the catheter’s proximal 4 lumen and the temperature curve b 3 in the pulmonary artery was ant alyzed by a Marquette electronics 7010 monitor (Milwaukee, Wisconsin). CO was calculated as the mean of 3 sequential measurements which varied by < lo%. A complete Doppler, Mmode, and 2-dimensional examination was performed in all pa● Tricusaid tients using a Hewlett Packard 4 t o NeTricuspid Sonos 1000 ultrasound system I 41 regwgitdan (Andover, Massachusetts), con6 7 3 45 1 2 nected with a 2.5-MHz probe. (COFisk+ COEcho~ (Umin) CO was evaluated by the left ventricular outflow method acFIGURE 2. a, Correlation between simultaneous Fickand -echocardiagra hic T (closedcirck) of cardiac output(CO)inpatients wi an1 without cording to the technique pro(ECHO]meowrernents (~ cides)tricuspid [email protected] regression lineisdrawnasa solidlineandthe posed by Dubin et al.13The left lineof identity isdoshed.b, BlandandAkrnanplotcomparing FickandDopplermeosurernenk d CO.Themeand“krencebetween measurements was–0.22 L/rein(dashed/ror- ventricular outflow diameter was izon#al Iii indicating an underestimationof Dopplermeasurements.OneSDdifference measured in systole from the was0.5 L/rein. parastemal long axis view just below the insertion of the aortic fasting, underwent simultaneous right heart catheter- CUSPS,and the area was then calculated according to ization and Doppler echocardiographic examination. the-formula 7rr2. Three measurements were a+erCO was simultaneously measured using Fick’s, ther- aged. The velocity of aortic flow was measured by modiltition, and Doppler echocardiographic meth- pulsed-wave Doppler from the apical 5-chamber view. The sample volume was positioned in the midods. Right-sided heart catheterization was performed dle of the outflow tract immediately below the aortic using a 7F Swan Ganz balloon-tipped catheter in- cusps and the time velocity integrals, recorded over serted into the right internal jugular vein and ad- 5 consecutive cycles (if patients were in sinus vanced through the right heart cavities into the rhythm) and 10 cycles (if in atrid”fibrillation), were pulmonary artery. Standard hemodynamic measure- digitized using the leading edge convention. Cardiac ments were obtained with the patient in a supine po- output was then calculated according to the formula: sition, using a Hewlett Packard transducer connected time velocity integral X left ventricular outjlow tract with a 7005 Marquette polygraph. Expired gases cross-sectional area X heart rate. Detailed data on were analyzed by a MGC CAD/NET system 2001 reproducibility of CO in patients with CHF have analyzer, and oxygen consumption was calculated been previously published by our group.lbTricuspid horn the difference between the values of environ- and mitral regurgitations were diagnosed by color mental and expired air. During the collection of ex- flow Doppler and graded on a 4-point scale.17J8They pired air a mixed venous blood sample was drawn were considered as significant only when >11 grade. 8
,’ .,
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THE AMERICAN JOURNAL OF CARDIO1OGY”
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15, 1996
ments was 0.5 L/rein (Figure 2b). Doppler echoc,ardiography a underestimated Fick CC) by an ● average of 0.22 L/rein, while no ● systematic error occurred using therrnodilution (Figure lb). In the subgroup of 34 patients ✘ with significant tricuspid regurgitation, the correlation between ✟✎ ✎ ✎❞✽ Fick and thermodilution mea❉ -1 surements of CO was poor (r = ● ● 0.68, SEE = 0.74), while in pa● ● tients without tricuspid regurgi● tation the correlation coefficient was 0.86 (SEE = 0.5 L/rein). In I 401 m+ m IRTR+ contrast, the correlation between [email protected] coca.swtwnwga.oumh Fick and Doppler echocardiog60 raphy measurements of CO was satisfactory in both subgroups (r b so , = 0.83, SEE = 0.45 L/rein and r = 0.91, SEE = 0.4 L/rein, re40 spectively) and, in’those with wicuspid regurgitation, it was significantly better (Z = 2.8, p = 0.0023) than that obtained by : ~ ~[ thermodilution. As shown in Figure 3a, the percent difference between Fick and thermodilution ● -20, a measurements was larger in the $ -4a, subgroups of patients with tricus● pid regurgitation but differences did not reach statistical significance (p = 0.07). The percent differences between Fick and Doppler echocardiographic meatsd carFIGURE 3. a, Percent differences between Fickandthermadibian measuremem surements were similar in each accarding tathepresence af tricuspid diacautput(CO)in4 groupsaf patienksdected &rencesbesubgroup (Figure 3b). WW~ ~+) and/af k cardiac autput(<3.5 I./minj.b, Percentd“ tweenFickand~ echacardiagmphic measurements mthe4 graups. .* We have previously shown CO measurements obtained both by Doppler that, in patients with advanced CHF, pulsed-wave echocardiographic and thermodilution methods were Doppler using the left ventricular outflow tract apcompared with those obtained by the Fick oxygen proach provides reproducible measurements of CO, method, considered the gold standard, by linear cor- the short-term variability being approximately 670.16 relation analysis and by the method proposed by The present study demonstrates that the noninvasive Bland and Altman. 19 me Conflation coefficients estimation of CO, provided by this method, besides were compared by Fisher’s Z test. Bland and Alt- being reproducible, is also accurate regardless of the man’s method consists in calculating the relative presence of low cardiac output and/or tricuspid remean differences (which reflect any systematic gurgitation. A number of Doppler methods have change between methods) and their SDS (which re- been proposed for measuring CO from the product flect the degree ‘of random variability) between of the mean blood flow velocity and the cross-secpaired measurements. Differences between measure- tional area at different points of the heart or aorta. ments in different groups were compared by analysis The left ventricular outflow tract method has several of the variance. Continuous variables were expressed advantages ( parallel insolation angle; relatively flat velocity profile; good velocity signal; circular crossby mean * 1 SD. Overall, the correlation between measurements of sectional area which hardly changes during the carCO obtained by the Fick and thermodilution meth- diac cycle) and in adult patients yielded the best resuits.10J3J4This is the first study which specifically ods was fairly good (r = 0.81,SEE = 0.68 L/tin) (Figure la). The SD difference was 0.7 L/rnin (Fig- investigates patients with advanced heart failure. The ure lb). The correlation between Fick ~d Doppler strong correlation between Doppler and Fick CO echoc&diographic values was stronger (r = 0190, measurements and the relatively narrow dispersion SEE = 0.5 L/rein) (Z = 4. D = 0.00002)( Figure of data we found in these selected patients is similar 2a), and the SD difference be[ween paired rnea&re- to that previously reported, using the same tech00
I
1
,..![ ~.~...~:’:
●
BRIEF REPORTS
711
nique, in more general populations.14A systematic underestimation of Doppler CO measurements was observed despite the use of the “leading edge convention’ for digitizing flow velocity curves. It was, however, smaller than that previously obtained by using the “modal convention.” 10”13 Although it is generally assumed that, from the apical approach, a parallel insolation of the left ventricular outflow tract can be easily acheived, small inaccuracies of the angle, particularly with respect to the azimuthal plane, are possible when enlarged ventricles are imaged; this may account for this underestimation of CO. The measurement of the left ventricular outflow tract diameter may be a source of error in Doppler CO.quantification. Small errors in this measurement (which is squared to calculate areas) may account for some discrepancy in results between Doppler and Fick CO observed in individual patients. To avoid this source of error Evangelista et a115have recently proposed simply using the left ventricular outflow tract mean blood velocity. They have shown that, in intensive care unit patients, this measurement was more accurate than its product by the cross-sectional area divided by the body surface area (i.e., estimated cardiac index) for assessing cardiac index. This implies that the cross-sectional area of the left ventricular outflow tract must be closely correlated with the body surface area while its direct measurement by 2-dimensional echocardiography is somewhat inaccurate. In our patients the correlation between mean left ventricular outflow tract velocity and cardiac index was weaker (r = 0.81) than in Evangelista’s study. Therefore, we chose the estimated CO. since it turned out to be more strongly correlated than the mean blood flow velocity. The discrepancy between ours and Evangelista’s results may be explained by the fact that in advanced chronic CHF the correlation between the cross-sectional area of left ventricular outflow tract and the body surface area is not as strong as in acute patients. Our findings demonstrate that in patients with advanced CHF the thermodilution method is fairly well correlated with the Fick method. In some patients, however, particularly when tricuspid regurgitation is present, thermodilution may lead to gross discrepancy in results. This suggests that, when a precise determination of CO is necessary since important clinical decisions will be made based on it (e.g., when we need to calculate arterial pulmonary resistances in a candidate for heart transplantation with a moderate to high transpulmonary pressure gradient), the Fick method should be preferred. In this population the agreement of Doppler echocardiographicwith Fick measurements of CO
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THE AMERICAN JOURNAL OF Cardiology@
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was closer than that obtained by thermodilution and independentfrom the presence of low CO and/ or tricuspid regurgitation.These data indicate that the Doppler echocardiographic method for measuring CO may represent a valid alternative to invasive methods. We believe that the reluctance to apply this simple and noninvasivemethod for clinical and researchpurposes in the setting of patients with CHF is no longer justified. AcknowledgementWe thank Rachel Stenner, MD, for her help in the preparation of this manuscript.
1.FagardR andConwayJ. Measurementofcsrdiacoutput:Fickprincipleusing catheterization.Eur Heart J 1990;11 (supplement):1–5. 2. BmnthwriifeMA, BradleyRD. Measurementof cardiscoutputby thermal dilutionin man. JApp[ Phy.riol1968;24:434-438. 3. GanzW, DonosgR, MarcusHS, FormsterJS, SwanHJ. A new technique for measurementof cardiacoutputby rhermodihrtion in man. Am J Cardiol 1971;27:392-396. 4. vsn GrondclleA, DitcheyRV, GrovesBM, WagnerWW, Jr., ReevesIT. Thermodihdimrmethodoverestimateslow cardiacoutput in humans. Am. J Physiol 1983; 245:H 690-692.
5. CigarroaRt3, LangeRA, WilliamsRH, BedottoJB, Hillis LD, Underestimationof cardiacoutputby thermodilutirrnin patientswitfrtricuspidregurgitation.Am J Med 1989;86:417-420. 6. KashtrmHI, MaitkmdA, SafernoTA, LichtcnsteinSV, ByrickRJ. Effects of tricuspidregurgitationon drermodilueion cardiacoutput:studiesin an animaf model.Can JAnaesth 1987;34:246–251. 7. KonishiT, NakanmraY, MoriiI, HimuraY, KumadaT, KawaiC. Compwisonof rfternmdiIudon and Fickmethodsfor measurementof crudiacoutputin tricuspidregurgitation.Am J Cmdiol 1992;70:538-539. 8. HamiltonAM, StevensonLW, Woo M, Child JS, Tillisch JH. Effect of tc’icuspidregurgitationon the reliabilityof the thermodilutioncardiacoutput techniquein congestiveheartfailure.AmJ Cardiol 1989;64:945-948. 9. MagninPA, StewartJA, Myers S, Von Ramm O, Kisslo JA. Combined DoppIerrmdphased-arrayechocardiographic estimationof cardiacoutput.Circulation 1981;13:388-392.
10.LewisFJ, KnoLC,NelsonJG,LimacherMC,QuinonesMA.PulsedDoppler echncardiograpbic determinationof strokevolumeandcardiacoutput:clinical vahdationof two new metheds using the apical window. Circulation 1984;70:425–431.
11. LabovifzAJ, Buckinghrmr TA,HabermehlK, NeIsonJ, KennedyHL, WilliamsGA. The effectsof sampfingsite on the,twn-dimensionalecho-Doppler determinationof cardiacoutput.AmHearr J 1985;109:327-332. 12. MehfaN, IyaweVI, CrmmrinAR, Bayley S, SaudersKB, BennettED. Validationof a Dopplertechniqueforbeat-to-beatmeaarrrement of cardiacoutput. ClinSci 1985;69:377-382. 13. DubinJ, WallersonDC,CodyRJ, DevereuxRB. Comparativeaccuracyof Dopplerechocardiographic methndsfor clinicalstrokevolumedetermination. AmHeart J 1990;120:116-123. 14.CoataAJ.Dopplerultrasonicmeaaurcmentofcardiacoutput:reproducibility snd validation.Eur Heart J 1990; 11(supplementI) 49–61. 15. EvangelistsA, Gsrcia-DorrrdoD, Garciadel CaatilloH, Gonzriles-Alujaa T, Soler-SolerJ. Cardiacindexquantificationby Dnpplerultmaoundin patients without left ventricular outflow tract abnormalities. J Am Co/l Cardiol 1995;25:710-716, 16.PozzofiM, Ca~molla S, CobelliF, TavazziL. Reproducibilityof Doppler indicesof left ventricularsystolicand diastolicfunctionin patientswithsevere chronicheartfailure.Eur Heart J 1995;16:194–200. 17. MiyatakeK, OkamotoM, KinoshitaN, OhtaM, KozucaT, SakakibaraH, NimuraY. Evahrationof tricuspidregurgitationby pulsedDopplerand twodimenaionrdechoardiography.Circulation 1982;66:777-784. 18. MiyatakeK, IzunriS, OkamotoM, KinoshitaN, AsonumaH, Nakagawa H,YamamotoK,TakamiyaM,SakakibaraH,NimuraY.Senriquantitative grading of severityof miti regurgitationby real time two dimensionalDoppler flowimagingtechnique.JArn Call Cardiol 1986;7:82-8. 19. BlandJM,Altman00. Statisticrdmethodsforassessingagmementbetween twometfmdsof clinicnlmeasurement.Cuncef1986;1:307-310.
SEPTEMBER
5, 1996
acute transmurrdmyocardialinfarction in human beings. Am J Cardiol h 1981;48:1023–1028. 2. MirvisDM.Spatialvariationof QT intervalsin normrdpersonsandpatients withacutemyucardialinfarction.JAm Coil Cardiol 1985;5:625–631. 3. Day CP, McCombJM, CampbellRWF. QT dispersion:an indicationof arrhythmiarisk in patientswith long QT intervaJs.Br Hear’fJ 1990;63:342– 344. 4. HiiJTY,WyseDG,GillisAM,DuffHJ, SolyloMA,MitchellLB.Prccordial QT”interval dispersion aa a marker of torsade de pointes. Circulation 1992;86:1376-1382. 5. LepeschkinE, SurawiczB. The measurementof the Q-T intervalof the electrccardiograrn. Circulation1958;17:378–388. 6. MurmyA,McLaughlinNB,BourkeJP,DoigJC,FomissSS,CampbellRWF. Errorsin manualmeasurementof QT interwds.Br Heart J 1994;71:386–390. Heart 7. BazettHC. An analysisof the time-relationsof electrucardiograma. 1920;7:353–370. 8. Pye M, Quirm AC,CobbeSM.QTintervafdispersion:a non-invasivemarker
of susceptibilitytu arrhythmiain patientswith sustainedverrtrictdararrhytfrmias?Br Heart J 1994;71:511-514. 9. Barr CS, NassA, FreemanM, Lang CC, StrutherzAD. QT dispersionand suddenunexpecteddeathin chronicbeartfailure.Z.ancet1994;343:327-329. 10. Day CP, JamesOFW, ButJerTJ, CampbellRWP. QT prolongationand suddendeathin patientswith afcoholicliver disease.Lmcet 1993;341:1423– 1428. 11. Buja G, MiorelliM, TrmiN P, MelaciniP, Nava A. Comparisonof QT dispersionin hypertmphiccardiomyopathybetweenpatientswith and without verrtricuJararrhythmiasand suddendeath.AmJ Cardiol 1993;72:973–976. 12. KautznerJ, Yi G, CaromJ, MalikM. Shortand long termreproducibility of QT, QTc, and QT dispersionmeasurementin healthy subjects. PACE 1994;17:928-937. 13. CowanJC, YusoffK, MooreM, AmosPA, GoldAE, BorrrkeJP, TansuphaswadikulS, CampbellRWF. Importanceof lead selectionin QT intervaf measurement.AmJ CardioZ 1988;61:83–87. 14. StattersD], MalikM, WardDE, CamrnAJ. QT Dispersion:Problemsof methodology aad clinical significance. J Cardiovascular Electrophysiol 1994;5:672–685. S, BourkeJP, MurrayA, Camp15. Cowrm JC, HiJtonCJ, Tansuphaawadikul
bell RWF. Sequenceof epicmdialrepularizatiouand configurationof OreT wave.Br Heart J 1988;60:424-433. 16. Yan GX, YamadaKA, KfeberAG, McHowatJ, Corr PB. Dissociation hehveencellularK’ loss,reductioninrepalarizationti me, andtissueATPlevels duringmyocardialhypoxiaand ischernia.Circ Res 1993;72;3:560-570. 17.PdoriSG,NapolitanoC,DiehlL, SchwartzP. DispersionoftheQTinterval. A markerof therapeuticefficacyin the idiupatic long QT syndrome.Circulation 1994;89:1681-1689. 18. KleimarrRB, HeuserSR. Outwardcurrentsin nnrmaland hypertruphied felineventricularmyocyt&.AmJPhysiol 1989;256:H1450–H1461. 19.FurukawaT, MyerburgRJ, FurukawaN, KirmrraS, BaasettAL.Metabulic inhibitionof ~~ and 1~differ%in feline left ventricularhypertrophy.Am J Physiol 1994;266:H1121-H1131. DJ, NabarrerM, GordmarurE. Alterationsof K+currentsin 20. Beuckelmsnm
1. CincaJ, FiguerasJ, TenorioL, Vane V, TrwrchsJ, SeguraR, F&s J. Time isolatedhumanventricularmyocytesfrompatientswithterminalheartfailure. cand rate dependenceof Q-T intervalchangesduringnoncomplicated Circ Res 1993;73:379–385.
EchocardiogruphyWith Thermodiktien for AssessingCardiacOutput in Advanced Congestive Heart Failure Comparison
of Ooppk
Andrea Gola, MD, Massimo Pozzoli, MD, Soccorso Capomolla, MD, Egidio Traversi, MD, Maurizio Sanarico, MS, Franco Cobelli, MD, and Iwigi Tavazzi, MD
n patients with chronic congestive “heart failure the quantification of cardiac ou~ut (CO) Iis (CHF) ‘m essentiai’part of the hemodynamic t%duation From the Salvatore Mau eri Foundation—institute of Research and Care, Rehabilitation Me 3 Ical Center, Mantescano, Pavia, Italy. Andrea Gala is recipient of a grant from the School of Cardiology, Departmentof InternalMedicine, Clinica Medica 1, University of Pavia, Pavia, Italy. Dr. Pozzoli’s address is: Salvatare Maugeri Foundation, Rehabilitation Medical Center, Depatiment of Cardiology, 27040 Montescano, Pavia, Italy. Manuscript received November 29, 1995; revised manuscriptreceivedand acceptedApril 4, 1996.
~
01996 by ExcerptaMedic., All rights reserved.
Inc.
that carries important therapeutic and prognostic implications. From among a variety of methods developed over the years to measure CO, the Fick oxygen method is probably the most accurate and is considered the standard reference technique.l This technique, however, requires right-sided heart catheterization and expired gas measurements, and cannot give instantaneous results. The thermodiluticm method, ~ application of the indicator dilution principle (in which the indicator is cold saiine), is the most widely used invasive method because it is easy 0002-9149/96/$15.00 Pll SOO02-9149(96]O040&7
to perform and allows instantaneous determination of CO-2,3It has been observed, however, that ther52 * 8 Age (yrs] modilution maybe inaccurate when low output states 24/49 Etiology (ixhemic/nonischemic) or tricuspid regurgitation, frequent occurrences in 33 [45%) New York Heart Association functional class chronic CHF, are present.4.5More recent studies have III-IV (patients) challenged these results, showing that thermodilu106 * 18 Systolic blaad pressure (mm Hg) 79 ~ 16 tion may be more accurate than previously Heart rate [beats/rein) 15 (20%) Atrial fibrillation (patients] claimed.b-8 To assess CO noninvasively, various 26 ~ 10 Left ventricular election fraction (%) Doppler echocardiographic methods have been pro34 (46%) Tricuspid regurgitation grade III-IV [patients) posed.9- 15From ~ong these, the left ventricular 36 (49%) Mitral regurgitation grade 111.IV[patients) outflow tract method has proved to be the most ac19 i 11 Pulmonary artsrry wedge pressure (mm Hg) 7*7 Right arial pressure (mm Hg) curate and reproducible, provided that no aortic re3.4 * 1.5 Cardiac output—Fick (L/rein] gurgitation is present. Despite this, its application for evaluating patients with CHF is fiir from being widespread, and a review of studies referenced in MedLine between 1994 and 1995, using the search terms Doppler echocardiography and cardiac outpw, revealed that a Doppler method for measuring CO was 8r used in only 38 clinical studies, . .’ of which only 6 concerned pa,’ 7 tients with CHF. ,“ o #.’ Accordingly,we directly coma o , ●’ 6 pared thermodilutionand Doppler ./ ,0 echocardiographic methods with ✌ ● ~, , ● the Fick oxygen method in patients with advanced CHF to ‘4 verify the agreement of thermo0 dilution with Fick’s method in 9 CO measurement particularly when low CO and/or tricuspid 6 ~, regurgitation is present, and esr 8 0.S1 tablish whether the Doppler ~wo.w method may represent ,avalid alCOFICK= 0.61+0.S7”COTH .. ternative to invasive techniques ~ L“” for measuring CO in these pa01234667 tients. 00 Fkk (I/miss) *. We studied 73 consecutive 4 patients (63 men and 10 women; t b mean age 52 f 8 years) with chronic advanced CHF owing to either ischemic (24 patients) or nonischemic (49 patients) dilated cardiomyopathy who were admitted to our heart failure unit and evaluated with a view to heart transplantation. Dilated cardiomyopathy was defined by i! the 2-dimensional echocardiou-z o ● Tstaus@d 0 graphic demonstration of a di4 lated left ventricle (left ventricI o NoTrksssspid ular end diastolic volume >78 ml/m2 of body surface area) with (COFkk + COTtsermastilutkn)F2 (lhnin) a left ventricular ejection fraction <3590. Patiedts with intracardiac . Mwe6n simuhseoustkssadiiutianandFickmeaswements FIGURE 1.a, Camdahan shunts, aortic valvular disease, d cardiac output(CO)Q~: :$s @osssd ciKM d {~ c+ ~wid and technically inadequate echorawn as a did Iisseand thelineof Asstiiyis WW9*. * &shed.6, Blanda3 Ahnsanplot camping Fickandthermadibtbrs mssasuremds of cardiograms were excluded. The rements, reparkdantheyssxk,arefsbtted dikmncesbetweenpairedmeasu CO.Thsr general characteristics of. the betwaenM6asssrsnsents i3 values (x axis).h meandi%renca against tlmir bycon- study group are summarized in nearlyzero~==blfine). b and2 = ofdikremss areirsdicakd Table I. All patients, who were TAME
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from the pulmonary artery and an arterial sample from the radial ar. tery. Their oxygen contents were 7 .“ measured using an ABL 500 ,# a .’ blood gas analyzer (Emdrupue, s ,0” /i Copenhagen, Denmark). CO was then calculated accordingly to the Fick formula. CO was considered to be low when <3.5 L/ min. The short-term variabilities, assessed in 20 CHF patients, of Q oxygen consumption at rest, arteriovenous oxygen difference, and Fick CO were 5Y0,7.8?40,and -0.s1 1 5.7%, respectively. co FCK=O.16+I,oi ‘co w The thermodilution method 1 o 1’was simultaneously applied to 01 284 S678 measure CO. Ten millilitres of iced saline solution (0°) were injected into the right atrium through the catheter’s proximal 4 lumen and the temperature curve b 3 in the pulmonary artery was ant alyzed by a Marquette electronics 7010 monitor (Milwaukee, Wisconsin). CO was calculated as the mean of 3 sequential measurements which varied by < lo%. A complete Doppler, Mmode, and 2-dimensional examination was performed in all pa● Tricusaid tients using a Hewlett Packard 4 t o NeTricuspid Sonos 1000 ultrasound system I 41 regwgitdan (Andover, Massachusetts), con6 7 3 45 1 2 nected with a 2.5-MHz probe. (COFisk+ COEcho~ (Umin) CO was evaluated by the left ventricular outflow method acFIGURE 2. a, Correlation between simultaneous Fickand -echocardiagra hic T (closedcirck) of cardiac output(CO)inpatients wi an1 without cording to the technique pro(ECHO]meowrernents (~ cides)tricuspid [email protected] regression lineisdrawnasa solidlineandthe posed by Dubin et al.13The left lineof identity isdoshed.b, BlandandAkrnanplotcomparing FickandDopplermeosurernenk d CO.Themeand“krencebetween measurements was–0.22 L/rein(dashed/ror- ventricular outflow diameter was izon#al Iii indicating an underestimationof Dopplermeasurements.OneSDdifference measured in systole from the was0.5 L/rein. parastemal long axis view just below the insertion of the aortic fasting, underwent simultaneous right heart catheter- CUSPS,and the area was then calculated according to ization and Doppler echocardiographic examination. the-formula 7rr2. Three measurements were a+erCO was simultaneously measured using Fick’s, ther- aged. The velocity of aortic flow was measured by modiltition, and Doppler echocardiographic meth- pulsed-wave Doppler from the apical 5-chamber view. The sample volume was positioned in the midods. Right-sided heart catheterization was performed dle of the outflow tract immediately below the aortic using a 7F Swan Ganz balloon-tipped catheter in- cusps and the time velocity integrals, recorded over serted into the right internal jugular vein and ad- 5 consecutive cycles (if patients were in sinus vanced through the right heart cavities into the rhythm) and 10 cycles (if in atrid”fibrillation), were pulmonary artery. Standard hemodynamic measure- digitized using the leading edge convention. Cardiac ments were obtained with the patient in a supine po- output was then calculated according to the formula: sition, using a Hewlett Packard transducer connected time velocity integral X left ventricular outjlow tract with a 7005 Marquette polygraph. Expired gases cross-sectional area X heart rate. Detailed data on were analyzed by a MGC CAD/NET system 2001 reproducibility of CO in patients with CHF have analyzer, and oxygen consumption was calculated been previously published by our group.lbTricuspid horn the difference between the values of environ- and mitral regurgitations were diagnosed by color mental and expired air. During the collection of ex- flow Doppler and graded on a 4-point scale.17J8They pired air a mixed venous blood sample was drawn were considered as significant only when >11 grade. 8
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ments was 0.5 L/rein (Figure 2b). Doppler echoc,ardiography a underestimated Fick CC) by an ● average of 0.22 L/rein, while no ● systematic error occurred using therrnodilution (Figure lb). In the subgroup of 34 patients ✘ with significant tricuspid regurgitation, the correlation between ✟✎ ✎ ✎❞✽ Fick and thermodilution mea❉ -1 surements of CO was poor (r = ● ● 0.68, SEE = 0.74), while in pa● ● tients without tricuspid regurgi● tation the correlation coefficient was 0.86 (SEE = 0.5 L/rein). In I 401 m+ m IRTR+ contrast, the correlation between [email protected] coca.swtwnwga.oumh Fick and Doppler echocardiog60 raphy measurements of CO was satisfactory in both subgroups (r b so , = 0.83, SEE = 0.45 L/rein and r = 0.91, SEE = 0.4 L/rein, re40 spectively) and, in’those with wicuspid regurgitation, it was significantly better (Z = 2.8, p = 0.0023) than that obtained by : ~ ~[ thermodilution. As shown in Figure 3a, the percent difference between Fick and thermodilution ● -20, a measurements was larger in the $ -4a, subgroups of patients with tricus● pid regurgitation but differences did not reach statistical significance (p = 0.07). The percent differences between Fick and Doppler echocardiographic meatsd carFIGURE 3. a, Percent differences between Fickandthermadibian measuremem surements were similar in each accarding tathepresence af tricuspid diacautput(CO)in4 groupsaf patienksdected &rencesbesubgroup (Figure 3b). WW~ ~+) and/af k cardiac autput(<3.5 I./minj.b, Percentd“ tweenFickand~ echacardiagmphic measurements mthe4 graups. .* We have previously shown CO measurements obtained both by Doppler that, in patients with advanced CHF, pulsed-wave echocardiographic and thermodilution methods were Doppler using the left ventricular outflow tract apcompared with those obtained by the Fick oxygen proach provides reproducible measurements of CO, method, considered the gold standard, by linear cor- the short-term variability being approximately 670.16 relation analysis and by the method proposed by The present study demonstrates that the noninvasive Bland and Altman. 19 me Conflation coefficients estimation of CO, provided by this method, besides were compared by Fisher’s Z test. Bland and Alt- being reproducible, is also accurate regardless of the man’s method consists in calculating the relative presence of low cardiac output and/or tricuspid remean differences (which reflect any systematic gurgitation. A number of Doppler methods have change between methods) and their SDS (which re- been proposed for measuring CO from the product flect the degree ‘of random variability) between of the mean blood flow velocity and the cross-secpaired measurements. Differences between measure- tional area at different points of the heart or aorta. ments in different groups were compared by analysis The left ventricular outflow tract method has several of the variance. Continuous variables were expressed advantages ( parallel insolation angle; relatively flat velocity profile; good velocity signal; circular crossby mean * 1 SD. Overall, the correlation between measurements of sectional area which hardly changes during the carCO obtained by the Fick and thermodilution meth- diac cycle) and in adult patients yielded the best resuits.10J3J4This is the first study which specifically ods was fairly good (r = 0.81,SEE = 0.68 L/tin) (Figure la). The SD difference was 0.7 L/rnin (Fig- investigates patients with advanced heart failure. The ure lb). The correlation between Fick ~d Doppler strong correlation between Doppler and Fick CO echoc&diographic values was stronger (r = 0190, measurements and the relatively narrow dispersion SEE = 0.5 L/rein) (Z = 4. D = 0.00002)( Figure of data we found in these selected patients is similar 2a), and the SD difference be[ween paired rnea&re- to that previously reported, using the same tech00
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nique, in more general populations.14A systematic underestimation of Doppler CO measurements was observed despite the use of the “leading edge convention’ for digitizing flow velocity curves. It was, however, smaller than that previously obtained by using the “modal convention.” 10”13 Although it is generally assumed that, from the apical approach, a parallel insolation of the left ventricular outflow tract can be easily acheived, small inaccuracies of the angle, particularly with respect to the azimuthal plane, are possible when enlarged ventricles are imaged; this may account for this underestimation of CO. The measurement of the left ventricular outflow tract diameter may be a source of error in Doppler CO.quantification. Small errors in this measurement (which is squared to calculate areas) may account for some discrepancy in results between Doppler and Fick CO observed in individual patients. To avoid this source of error Evangelista et a115have recently proposed simply using the left ventricular outflow tract mean blood velocity. They have shown that, in intensive care unit patients, this measurement was more accurate than its product by the cross-sectional area divided by the body surface area (i.e., estimated cardiac index) for assessing cardiac index. This implies that the cross-sectional area of the left ventricular outflow tract must be closely correlated with the body surface area while its direct measurement by 2-dimensional echocardiography is somewhat inaccurate. In our patients the correlation between mean left ventricular outflow tract velocity and cardiac index was weaker (r = 0.81) than in Evangelista’s study. Therefore, we chose the estimated CO. since it turned out to be more strongly correlated than the mean blood flow velocity. The discrepancy between ours and Evangelista’s results may be explained by the fact that in advanced chronic CHF the correlation between the cross-sectional area of left ventricular outflow tract and the body surface area is not as strong as in acute patients. Our findings demonstrate that in patients with advanced CHF the thermodilution method is fairly well correlated with the Fick method. In some patients, however, particularly when tricuspid regurgitation is present, thermodilution may lead to gross discrepancy in results. This suggests that, when a precise determination of CO is necessary since important clinical decisions will be made based on it (e.g., when we need to calculate arterial pulmonary resistances in a candidate for heart transplantation with a moderate to high transpulmonary pressure gradient), the Fick method should be preferred. In this population the agreement of Doppler echocardiographicwith Fick measurements of CO
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was closer than that obtained by thermodilution and independentfrom the presence of low CO and/ or tricuspid regurgitation.These data indicate that the Doppler echocardiographic method for measuring CO may represent a valid alternative to invasive methods. We believe that the reluctance to apply this simple and noninvasivemethod for clinical and researchpurposes in the setting of patients with CHF is no longer justified. AcknowledgementWe thank Rachel Stenner, MD, for her help in the preparation of this manuscript.
1.FagardR andConwayJ. Measurementofcsrdiacoutput:Fickprincipleusing catheterization.Eur Heart J 1990;11 (supplement):1–5. 2. BmnthwriifeMA, BradleyRD. Measurementof cardiscoutputby thermal dilutionin man. JApp[ Phy.riol1968;24:434-438. 3. GanzW, DonosgR, MarcusHS, FormsterJS, SwanHJ. A new technique for measurementof cardiacoutputby rhermodihrtion in man. Am J Cardiol 1971;27:392-396. 4. vsn GrondclleA, DitcheyRV, GrovesBM, WagnerWW, Jr., ReevesIT. Thermodihdimrmethodoverestimateslow cardiacoutput in humans. Am. J Physiol 1983; 245:H 690-692.
5. CigarroaRt3, LangeRA, WilliamsRH, BedottoJB, Hillis LD, Underestimationof cardiacoutputby thermodilutirrnin patientswitfrtricuspidregurgitation.Am J Med 1989;86:417-420. 6. KashtrmHI, MaitkmdA, SafernoTA, LichtcnsteinSV, ByrickRJ. Effects of tricuspidregurgitationon drermodilueion cardiacoutput:studiesin an animaf model.Can JAnaesth 1987;34:246–251. 7. KonishiT, NakanmraY, MoriiI, HimuraY, KumadaT, KawaiC. Compwisonof rfternmdiIudon and Fickmethodsfor measurementof crudiacoutputin tricuspidregurgitation.Am J Cmdiol 1992;70:538-539. 8. HamiltonAM, StevensonLW, Woo M, Child JS, Tillisch JH. Effect of tc’icuspidregurgitationon the reliabilityof the thermodilutioncardiacoutput techniquein congestiveheartfailure.AmJ Cardiol 1989;64:945-948. 9. MagninPA, StewartJA, Myers S, Von Ramm O, Kisslo JA. Combined DoppIerrmdphased-arrayechocardiographic estimationof cardiacoutput.Circulation 1981;13:388-392.
10.LewisFJ, KnoLC,NelsonJG,LimacherMC,QuinonesMA.PulsedDoppler echncardiograpbic determinationof strokevolumeandcardiacoutput:clinical vahdationof two new metheds using the apical window. Circulation 1984;70:425–431.
11. LabovifzAJ, Buckinghrmr TA,HabermehlK, NeIsonJ, KennedyHL, WilliamsGA. The effectsof sampfingsite on the,twn-dimensionalecho-Doppler determinationof cardiacoutput.AmHearr J 1985;109:327-332. 12. MehfaN, IyaweVI, CrmmrinAR, Bayley S, SaudersKB, BennettED. Validationof a Dopplertechniqueforbeat-to-beatmeaarrrement of cardiacoutput. ClinSci 1985;69:377-382. 13. DubinJ, WallersonDC,CodyRJ, DevereuxRB. Comparativeaccuracyof Dopplerechocardiographic methndsfor clinicalstrokevolumedetermination. AmHeart J 1990;120:116-123. 14.CoataAJ.Dopplerultrasonicmeaaurcmentofcardiacoutput:reproducibility snd validation.Eur Heart J 1990; 11(supplementI) 49–61. 15. EvangelistsA, Gsrcia-DorrrdoD, Garciadel CaatilloH, Gonzriles-Alujaa T, Soler-SolerJ. Cardiacindexquantificationby Dnpplerultmaoundin patients without left ventricular outflow tract abnormalities. J Am Co/l Cardiol 1995;25:710-716, 16.PozzofiM, Ca~molla S, CobelliF, TavazziL. Reproducibilityof Doppler indicesof left ventricularsystolicand diastolicfunctionin patientswithsevere chronicheartfailure.Eur Heart J 1995;16:194–200. 17. MiyatakeK, OkamotoM, KinoshitaN, OhtaM, KozucaT, SakakibaraH, NimuraY. Evahrationof tricuspidregurgitationby pulsedDopplerand twodimenaionrdechoardiography.Circulation 1982;66:777-784. 18. MiyatakeK, IzunriS, OkamotoM, KinoshitaN, AsonumaH, Nakagawa H,YamamotoK,TakamiyaM,SakakibaraH,NimuraY.Senriquantitative grading of severityof miti regurgitationby real time two dimensionalDoppler flowimagingtechnique.JArn Call Cardiol 1986;7:82-8. 19. BlandJM,Altman00. Statisticrdmethodsforassessingagmementbetween twometfmdsof clinicnlmeasurement.Cuncef1986;1:307-310.
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