Echocardiography in Liver Transplant Candidates

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Echocardiography in Liver Transplant Candidates

Anubhav Garg, MD, William F. Armstrong, MD

Ann Arbor, Michigan

Involvement of the cardiovascular system in patients with end-stage liver disease (ESLD) is well recognized

and may be seen in several scenarios in adult liver transplantation (LT) candidates. The hemodynamic

effects of ESLD may result in apparent heart disease, or in some instances may mask cardiac disease.

Alternatively, cardiac disease can occasionally be the underlying etiology of ESLD. LT imposes significant

hemodynamic stresses, with cardiovascular complications accounting for considerable perioperative

mortality and morbidity. Pre-operative assessment of the cardiac status of LT candidates is thus critically

important for risk stratification and management. Cardiac imaging plays an integral role in the assessment

of LT candidates. In this review, we discuss the role of cardiac imaging, including transthoracic echocardi-

ography with Doppler and contrast enhancement, noninvasive functional assessment for routine pre-

operative assessment of coronary artery disease, and transesophageal echocardiography in select cases to

aid in intra-operative fluid management and monitoring in LT candidates. (J Am Coll Cardiol Img 2013;6:

105–19) © 2013 by the American College of Cardiology Foundation

ularo re

nvolvement of the cardiovascular system inend-stage liver disease (ESLD) is well recog-nized and results in several distinct clinicalscenarios. The hemodynamic effects of ESLD

may result in apparent heart disease or in someinstances may mask cardiac disease. ESLDresults in a constellation of secondary cardio-vascular effects referred to as “cirrhotic car-diomyopathy”—a form of cardiac dysfunctioncharacterized by cardiac structural changes, di-astolic dysfunction, and baseline supernormalcardiac output with impaired contractile re-serve in response to stress (1). Liver trans-plantation (LT) imposes significant hemody-namic stresses with cardiovascular eventsreported in up to 70% of LT recipients (2).Less common cardiovascular abnormalities inLT candidates include pulmonary heart dis-ease, pericardial effusions, and intracardiac

From the Department of Internal Medicine, Division of CardiovascAnn Arbor, Michigan. The authors have reported that they have nto disclose.

Manuscript received August 17, 2012; revised manuscript received No

shunts (1). Occasionally, pre-operative eval-uation of the LT candidate reveals evidenceof cardiac disease as the underlying etiologyof ESLD.

Cardiac imaging plays an integral role in theassessment of LT candidates. While computedtomography (CT), cardiac magnetic resonance(CMR), and angiography have all been usedfor the characterization of cardiac disease inESLD, echocardiography remains the mostcommonly utilized technique. In this review,we discuss the role of cardiac imaging includingtransthoracic echocardiography (TTE) withDoppler and contrast enhancement, noninva-sive functional assessment for pre-operativeassessment of coronary artery disease (CAD),and transesophageal echocardiography (TEE)in select cases to aid in intraoperative fluidmanagement.

Disease, University of Michigan Medical Center,lationships relevant to the contents of this paper

vember 2, 2012, accepted November 9, 2012.

http://dx.doi.org/10.1016/j.jcmg.2012.11.002

echocardiography

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Cardiovascular Hemodynamics and Disease in ESLD

Hemodynamics of ESLD cirrhotic cardiomyopathy. Pa-tients with ESLD have decreased sinusoidal, butincreased peripheral, nitric oxide production, lead-ing to portal hypertension and splanchnic andperipheral vasodilatation (3,4). ESLD is also char-acterized by an expansion and redistribution ofcirculating blood volume, resulting in relativesplanchnic hypervolemia and effective central hypo-volemia (3,5). The combination of decreased sys-temic vascular resistance with central hypovolemialeads to a hyperdynamic circulatory state that isunique to patients with ESLD (4–9). This hemo-

dynamic state results in increased pulmo-nary and systemic flows at baseline withhigh normal or elevated right ventricular(RV), pulmonary artery, and left-atrial(LA) or pulmonary capillary wedge pres-sures (Table 1) (4,5). This hemodynamicprofile is noted in patients with ESLD notcomplicated by pulmonary vascular diseaseor primary cardiac disease (Figs. 1, 2, and 3;Online Videos 1 and 2).

In the LT candidate, pre-operative car-diac compromise and overt heart failure israrely present as left-ventricular (LV) dys-function is masked by the peripheral vaso-dilatation associated with ESLD (7).However, an impaired cardiac ventricularresponse to physiological or pharmacolog-ical stress may be present despite theincrease in baseline cardiac output (8,9).This impaired hemodynamic response tostress in the absence of primary cardiacdisease is the hallmark of cirrhotic cardio-myopathy (8,9). This latent LV systolicdysfunction results from a combinationof the following: 1) decreased beta-

adrenergic receptor density and function; and 2)negative inotropic effect of endocannabinoids andnitric oxide, both of which are upregulated in thesetting of cirrhosis (1,3). The prevalence of cirrhoticcardiomyopathy is unknown as it is often difficult toestablish the diagnosis due to the normal or hyper-dynamic cardiac function at rest and the presence ofconcurrent primary cardiac disease (3,10).

In addition to masked systolic dysfunction, cir-rhotic cardiomyopathy may be accompanied bydiastolic dysfunction and structural and electricalcardiac abnormalities (8,9,11). The increased myo-cardial stiffness found in patients with cirrhosis is

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thought to reflect a combination of LV hypertrophy

(LVH), myocardial fibrosis, and subendothelialedema secondary to ESLD (4,5,9). Several studieshave documented impaired ventricular relaxation incirrhotic patients noted as a nonsignificant increasein the E-wave velocity, significantly increasedA-wave velocity, increased deceleration time, anddecreased E/A ratio when compared to controls(6,11,12) (Fig. 4). Patients with ascites have morepronounced diastolic dysfunction than patientswithout ascites (6,13).

A recent autopsy study of 133 patients withcirrhosis and no known history of heart diseaserevealed significant cardiac abnormalities in 43%,with cardiomegaly and LVH the most common

Table 1. Baseline Hemodynamic Changes in PatientsWith ESLD

Hemodynamic Parameter Changes

Systemic circulation Plasma volume 1, total bloodvolume 1, noncentral bloodvolume 1, central bloodvolume 2 ↔, arterial bloodpressure ↔ 2, systemicvascular resistance 2, heartrate 1, cardiac output 1

Cardiac hemodynamics LA volume 1, LV volume 1 ↔,right atrial volume ↔ 1 2,RV volume ↔ 1 2, RApressure ↔ 1, RV end-diastolic pressure ↔,pulmonary capillary wedgepressure ↔, LV end-diastolicpressure 1 ↔

Pulmonary circulation Pulmonary blood flow 1,pulmonary artery pressure ↔1, pulmonary vascularresistance ↔ 1 2

↔ � No change; 1 � increase; 2 � decrease; ESLD � end-stage liverdisease; LA � left-atrial; LV � left-ventricular; RA � right-atrial; RV � rightventricular.

Figure 1. Apical 4-Chamber View Recorded in a PatientWith ESLD

Note the left atrial (LA) dilation (LA area, 25.5 cm2) and hyperdy-namic left ventricular (LV) function (LV ejection fraction, 72%).(See Online Video 1). ESLD � end-stage liver disease.

A B B R E V I A T I O N S

A N D A C R O N YM S

AASLD � American Associat

for the Study of Liver Diseas

ACCF � American College o

Cardiology Foundation

AHA � American Heart

Association

CAD � coronary artery disea

DSE � dobutamine stress

echocardiography

ESLD � end-stage liver dise

HPS � hepatopulmonary

syndrome

LT � liver transplantation

LV � left ventricle/ventricul

LVH � left-ventricular

hypertrophy

LVOTO � left-ventricular

outflow tract obstruction

PPH � portopulmonary

hypertension

TTE � transthoracic

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findings (14). Numerous studies have evaluatedcardiac chamber sizes in patients with ESLD al-though with conflicting results. Using echocardiog-raphy, Pozzi et al. (6) and Abd-El-Aziz et al. (11)found that LA size was significantly larger but LVsize was similar in cirrhotic patients as compared tocontrols. In contrast, Finucci et al. (12) foundsignificantly increased left atrial volumes, LV enddiastolic volumes, and stroke volumes in cirrhoticpatients compared to controls. In contrast, right-sided cardiac chamber sizes can be reduced, normalin size, or enlarged, likely depending on the pres-ence of accompanying pulmonary vascular disease(5). Mild LVH is a common finding in cirrhoticcardiomyopathy (6,11,12). Although the mecha-nism of LVH is not completely understood, it ispresumed to result from a combination of me-chanical overload in the setting of chronicallyincreased cardiac output and activation of theneuroendocrine system, especially in the settingof ascites (6,13).

Coronary Artery Disease

The prevalence of CAD in ESLD previously wasthought to be lower than in the general populationrelated to abnormal synthetic liver function result-ing in lower cholesterol, lower blood pressure, andhigher levels of circulating estrogens (15,16). Morerecent studies have demonstrated that LT candi-dates have a significantly greater prevalence ofCAD than previously thought (15). In studiesutilizing cardiac catheterization for all enrolledpatients, the prevalence of CAD has ranged from18% to 27% (Table 2) (17–19). Risk factors for the

resence of CAD included older age, male gen-er, hypertension or diabetes, and non–alcohol-elated etiology of cirrhosis (17–19). Studies havelso revealed a significant burden of unrecog-ized, asymptomatic CAD (1,15). Carey et al.17) reported that 13.3% of LT candidates withoderate or severe coronary stenosis were asymp-

omatic, presumably due to the masking effect ofoor functional status.ESLD patients with CAD have worse outcomes

han patients without CAD (20). In patients withnown CAD who underwent LT, Plotkin et al.20) reported a 30-day 25% mortality rate, anverall mortality rate of 50%, and morbidity rate of1%. Cardiovascular disease continues to contributeo late mortality after transplantation due to theecondary development of hypertension, hyperlip-
demia, diabetes, and obesity from chronic immu- w
nosuppression (15,16). Cardiovascular disease is thesecond most common cause of death (21%) 1 yearafter transplantation (21) and the third most com-mon cause (21%) 3 years after transplantation (22).With greater emphasis on improved assessment andrevascularization of CAD pre-operatively, Diedrichet al. (23) recently showed an improvement in theoverall mortality rate to 26% and morbidity rateto 38%.Noninvasive assessment of the liver transplant candi-date. Currently, the American Association for the

tudy of Liver Diseases (AASLD) recommendsoutine TTE for all LT candidates for the assess-ent of chamber sizes, hypertrophy, systolic and

iastolic function, valvular function, and LV out-ow tract obstruction (LVOTO) (24). In patients

Figure 2. TVIs Recorded in a Patient With ESLD

Note the upper normal to elevated time-velocity integrals (TVIs) ofoutflow track of 27 cm (top panel) and LV outflow track of 39 cmative of the high-flow state. Abbreviations as in Figure 1.

the right ventricular(bottom panel) indic-

ith ESLD, TTE should reveal normal or super-


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normal LV systolic function at rest; the finding of“normal” or reduced ejection fraction should raisesuspicion of an underlying cardiomyopathy or CADand merits further evaluation. Other imaging mo-dalities have been utilized, including single photonemission computed tomography (SPECT), com-puted tomography angiography (CTA), and CMR,although the bulk of the available data are withechocardiography.

ESLD, especially if complicated by hepatomeg-aly and ascites, may pose distinct problems withimaging. These issues may include technical diffi-culty with acquisition of high-quality images andissues relating to accurate diagnoses, which arespecific to the pathophysiology of ESLD. In gen-eral, with CTA or CMR, the only technical issuesinclude control of respiratory rate and/or breathholding in patients with ascites who may have

Elevation of Right Ventricular Systolic Pressure in a Patient Withse

flow track view revealing high-velocity inflow from the inferiorith a high flow state. (B) Tricuspid regurgitation jet revealing am/s corresponding to a right ventricular to right-atrial pressureconsistent with mild elevation of pulmonary artery pressures.

respiratory compromise while supine. Other than

this, the relative and absolute contraindications arethe same in the ESLD patient as in the generalpopulation. When utilizing SPECT for assessmentof CAD, diaphragmatic attenuation may be notedrelated to elevation of the diaphragm and/or hepa-tomegaly shadowing the inferior port of the heartand thus mimicking an inferior perfusion defect.

Echocardiographic imaging of the patient withESLD may be complicated by ascites, which limitsthe ability to image from the subcostal position andmay alter the orientation of the heart within thethorax such that off-axis views and unconventionalimaging windows are necessary. In general, acqui-sition of clinical quality images is feasible in themajority of patients. The echocardiographer mustrecognize the anticipated physiological changes inESLD, including high volume flow and mild de-grees of chamber enlargement. On occasion, ascitesmay distort the contour of the LV and result inartifactual pseudodyskinesis of the posterior wall(Fig. 5; Online Video 3).

Assessment for underlying CAD is often accom-plished with dobutamine stress echocardiography(DSE), which is presumed to mimic the hemody-namic stress of LT (15). Initial studies evaluatingDSE in the LT candidate were promising (Table 3).Donovan et al. (25) compared DSE to coronaryangiography in a limited subset of 18 patients andfound a sensitivity of 75% and specificity of 57%.Subsequently, Plotkin et al. (26) evaluated a higherrisk group of patients with ESLD and found asensitivity of 100% and specificity of 100% forsignificant CAD (coronary stenosis �70%). Morerecent studies have cast a doubt on the utility ofDSE as a screening tool for CAD in this patientpopulation (Table 3). In evaluating 64 patients forobstructive CAD (stenosis �50%) with DSE,Harinstein et al. (27) found a sensitivity of 17% andspecificity of 88%. Similarly, Patel et al. (19) eval-uated 205 patients for severe CAD (stenosis �70%)with DSE and found a sensitivity of 60% andspecificity of 69% (Fig. 6; Online Video 4).

The prognostic value of DSE in predicting in-traoperative cardiac events has also been examined.Umphrey et al. (28) found that maximum heart rateachieved during DSE may be a predictor of adversecardiovascular events in the perioperative setting.However, both Williams et al. (29) and Findlay etal. (30) demonstrated poor correlation between apositive DSE and significant intraoperative cardiacevents (Table 4). It has been suggested that theconflicting diagnostic performance of DSE may be

Figure 3. Flow RelatedEnd Stage Liver Disea

(A) Right ventricular invena cava consistent wpeak gradient of 3.09gradient of 38 mm Hg(See Online Video 2.)

due to the differing study definitions of CAD,




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retrospective analysis, lack of identification of mul-tivessel disease and a high rate of nondiagnosticstudies related to inadequate heart rate response(15). Finally the low accuracy for predicting eventsmay be related to an etiology for events not depen-dent on obstructive CAD.

SPECT has been evaluated as a screening toolfor CAD in LT candidates, likewise with variableresults (Table 3). Davidson et al. (31) evaluatedstress myocardial perfusion imaging in LT candi-dates without known CAD and found a sensitivityof 37% and specificity of 63% when compared tocoronary angiography. Defining only reversible per-fusion abnormalities as indicative of a positiveSPECT study, Aydinalp et al. (32) revealed asensitivity of 100% and specificity of 61% whencompared to coronary angiography. In this study,however, fixed perfusion defects were classified asnormal or minimal CAD (32). Zoghbi et al. (33)examined the usefulness of SPECT to predictcardiovascular complications and found that a nor-mal SPECT study had a 99% negative predictivevalue for perioperative cardiac events, although thiswas in a low-risk cohort of patients. A more recentstudy found a low proportion of positive stressmyocardial perfusion imaging results (7%) in apopulation of 772 consecutive adult LT candi-dates—a finding that is incongruous with the re-ported prevalence of CAD in this patient popula-tion (34). This study also reported a substantiallylower rate of cardiovascular complications whichwere not well predicted by pre-transplant imaging.

Several newer modalities are being evaluated forthe noninvasive assessment of CAD in LT candi-dates. Coronary artery calcification scoring has beenwell validated as an independent risk factor forCAD in the general population (35), but currently,there are only limited data utilizing this modality inLT candidates (36,37). Cardiac CTA is emergingas a potential noninvasive alternative for pre-operative evaluation. Keeling et al. (38) reported aprevalence of CAD of 90.8% in LT candidatesusing CTA, although without confirmation withcoronary angiography. Cassagneau et al. (39) re-cently compared the prognostic value of CTA withDSE and found a comparably high negative pre-dictive value for major cardiac adverse events withCTA and DSE. Although CTA appears promising,several limitations exist for this patient populationincluding the need for tight heart-rate control,breath-holding during the test, and the potential forcontrast-induced renal impairment (15). Keeling et
al. (38) revealed that over a quarter of patients had
poor image quality due to these limitations. CMR isa developing technology that would allow for acomplete noninvasive assessment of the LT candi-date but has not been studied in this patientpopulation and shares many of the limitations asCTA (15).

Coronary angiography remains the gold standardfor the diagnosis of CAD. It has been suggestedthat coronary angiography should be used in all LTcandidates with known CAD due to the high ratesof morbidity and mortality in this subset of LTcandidates (1,16). However, coronary angiographyshould not be used as the initial screening test as itis invasive, carries increased risk in ESLD patientswho may be coagulopathic, and can lead to

Figure 4. Doppler Evidence of Diastolic Dysfunction

Transmitral Doppler inflow and annular velocity in a patient with ESabnormal mitral inflow and annular tissue velocities consistent withtion. This patient also appears in Figure 1. Abbreviation as in Figure

LD documentingdiastolic dysfunc-

contrast-induced renal failure (38).

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Based on existing evidence, the AASLD, theAmerican Heart Association (AHA), and theAmerican College of Cardiology Foundation(ACCF) have established guidelines for pre-operative CAD assessment in LT candidates(24,40). These guidelines agree that LT candidatesshould undergo an evaluation for CAD based onthe presence of risk factors. Depending on thecommittee, these risk factors include a history ofsmoking, diabetes mellitus, hypertension, hyperlip-idemia, clinical or family history of heart disease,LVH, or age �50 years versus �60 years (24,40).

he AASLD also states that DSE appears to be anffective screening test in this setting with coro-ary angiography recommended for all positiveesults. It should be emphasized that the recom-endation for use of DSE is a consensus opinion

nd not one based on robust comparative trials.n clinical practice, multiple modalities haveound reasonable success, and in the absence ofore robust data, the choice of provocative test-

ng in LT candidates is probably best determinedy local expertise.

Other Cardiovascular Considerations

LVOTO and hypertrophic cardiomyopathy. The base-line hyperdynamic systolic function and low periph-eral vascular resistance in the setting of LVHpredisposes LT candidates to hypotension or todevelopment of LVOTO during DSE or in thesetting of decreased intraoperative preload. Maraj etal. (41) found that 43% of patients had inducibleLVOTO on pre-operative DSE, defined as anoutflow tract gradient of �36 mm Hg (Fig. 7;Online Video 5). These patients had a significantlyincreased risk of intraoperative hypotension but nosignificant increase in post-operative mortality (41).In rare cases, the LT candidate may have LVOTOsecondary to concomitant hypertrophic cardiomy-opathy (42,43). The finding of LVOTO necessi-

Table 2. Prevalence of CAD in LT Candidates

Author (Year) (Ref. #)No. ofPatients

Patient Age,yrs

Prevalence ofCAD, %

Carey et al. (1995) (17) 37 50–71 27*

Tiukinhoy-Laing et al.(2006) (18)

161 57 � 7 26†

Patel et al. (2011) (19) 420 56 � 8 18*

*Defined as coronary stenosis �30% on coronary angiography. †Defined ascoronary stenosis �50% on coronary angiography.

CAD � coronary artery disease; LT � liver transplant.

tates careful intraoperative monitoring with

avoidance of hypovolemia, tachycardia, and ino-tropic agents. Furthermore, in the setting ofLVOTO and diastolic dysfunction, invasive mea-surement of cardiac filling pressures may provideerroneous information for assessment of ventric-ular volume, especially in the post-reperfusionperiod (42). Intraoperative TEE can play a crit-ical role for continuous monitoring of ventricularvolumes and dynamic LVOTO, guiding the useof volume resuscitation and vasopressor therapy(42,43).Valvular heart disease. Limited data exist on theincidence and relevance of valve dysfunction in LTcandidates. In a retrospective study, Alper et al. (44)reported that 27.5% of LT candidates had evidenceof either mitral regurgitation, tricuspid regurgita-tion, or both. Furthermore, systemic vascular resis-tance was significantly decreased in patients withmitral regurgitation, and cardiac output was signif-icantly increased in patients with isolated mitralregurgitation or mitral and tricuspid regurgitationas compared to controls (44). Although these he-modynamic changes did not affect overall mortality,more patients with either isolated mitral regurgita-tion or mitral and tricuspid regurgitation experi-enced intraoperative hypotension requiring vaso-pressor therapy (44).

Aortic stenosis results in LV pressure overloadwith compensatory ventricular hypertrophy and de-creased LV compliance. These hemodynamics areexaggerated during LT due to profound fluid shiftsresulting in a sudden decrease in preload during

Figure 5. Parasternal Short-Axis View Recording in aPatient With ESLD

Note the posterior compression of the LV by the ascites (longarrow) resulting in a D-shaped LV with flattening of the posteriorwall in diastole (arrowheads). In the real-time clip, note the restitu-tion of circular LV geometry in systole resulting in posterior wall pseu-dodyskinesis. Abbreviations as in Figure 1. (See Online Video 3.)




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liver resection and impaired myocardial contractilityduring the post-reperfusion syndrome. The pres-ence of severe aortic stenosis in the LT candidaterequires a collaborative approach, and only casereports have documented successful LT in thesepatients (45,46). Although TTE is an importantnoninvasive method for evaluating the severity ofaortic stenosis, it requires careful interpretation in

Figure 6. DSE Performed 6 Months Following Liver Transplanta

Pre-operative dobutamine stress echocardiography (DSE) had reveacoronary artery disease (CAD). The patient subsequently developedfindings consistent with left anterior descending coronary artery isc

Table 3. Accuracy of DSE and SPECT Imaging in the Detection o

Type of Stress Testing/Author (Year) (Ref. #) No. of Patien

DSE

Donovan et al. (1996)* (25) 18

Plotkin et al. (1998)† (26) 40

Harinstein et al. (2008)* (27) 64

Harinstein et al. (2008)† (27) 64

Patel et al. (2011)‡ (19) 205

SPECT imaging

Davidson et al. (2002)† (31) 83

Aydinalp et al. (2009)‡§ (32) 93

*CAD defined as coronary stenosis �50% in 1 or more arteries. †CAD defined a�70% in 1 or more arteries. §SPECT imaging considered non-ischemic if norm

DSE � dobutamine stress echocardiography; NPV � negative predictive vtomography; other abbreviations as in Table 2.

ESLD. As a result of high transvalvular flows,reliance on aortic valve gradients alone may resultin overestimation of the degree of obstructionand calculation of aortic valve area is thus essen-tial (45). Although additional echocardiographicfindings such as LVH can support the diagnosisof advanced aortic stenosis, it can be present incirrhotic cardiomyopathy alone (45). When echo-

a normal hyperdynamic response and suggested the absence ofst discomfort following transplant and a repeat study revealedia with dyskinesis of the distal septum (arrow) at peak dobut-

AD in LT Candidates

Sensitivity, % Specificity, % PPV, % NPV %

75.0 57.1 33.3 88.9

100.0 100.0 100.0 100.0

16.7 87.5 44.4 63.6

12.5 85.4 22.2 74.5

60 68.9 21.1 92.5

36.8 62.5 22.6 76.9

100.0 60.9 15.0 100.0

onary stenosis �70% in 1 or more arteries. ‡CAD defined as coronary stenosisrfusion or fixed defects.PPV � positive predictive value; SPECT � single photon emission computed

tion

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amine. (Upper left: rest, upper right: low dose, lower left: peak dose, lower right: recovery.) (See Online Video 4.)

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cardiographic data are in question, cardiac cath-eterization should be performed to assess thehemodynamic severity.Hepatopulmonary syndrome. Hepatopulmonarysyndrome (HPS) is characterized by the presence ofabnormal intrapulmonary vascular dilatations re-

ng a Normal Hyperdynamic Response and Evidence of Dynamiction

ote the systolic anterior motion of the mitral valve (arrow) andic LV outflow track gradient of 86.6 mm Hg. Abbreviations as innline Video 5.)

Table 4. Prognostic Value of DSE for Significant Intraoperative

Author, Year, (Ref. #) Number of Patients

Williams et al. (2000)* (29) 71

Findlay et al. (2005)† (30) 73

*Significant intraoperative cardiac event defined as arrhythmia, cardiac arrest, or dT measured after transplantation.Abbreviations as in Table 3.

sulting in a compromise of pulmonary gas exchangein patients with advanced liver disease (47,48). Theprevalence of HPS is approximately 20% in LTcandidates but clinically significant HPS with arte-rial hypoxemia is identified in �5% (47). Thepathogenesis of HPS is linked to an imbalancebetween vasoconstrictors and vasodilators leading topulmonary vascular dilatation at the pre-capillaryand capillary level (47,49). This results in intrapul-monary shunting, ventilation–perfusion mismatch,and hypoxemia with clinical presentation of pro-gressive hypoxia, dyspnea, and cyanosis (48,50). LTmay be curative in some patients with mild tomoderate HPS (48). The diagnosis of HPS isestablished based on 3 criteria: evidence of chronicliver disease, hypoxemia at rest, and evidence ofintrapulmonary vascular shunting (49,50). The goldstandard for demonstration of intrapulmonaryshunting is saline contrast echocardiography(49,50) (Fig. 8; Online Video 6). Appearance ofagitated saline on the left side of the heart in HPSis dependent on the time it takes for transpulmo-nary blood flow and can occur within 4 to 5 beats inpatients with increased cardiac output or be delayedby 8 to 10 beats if the cardiac output is depressed.With intrapulmonary shunting, contrast will bevisualized in the pulmonary veins and may continueto appear in the left side of the heart even after therehas been clearance of saline from the right side ofthe heart. This is in contrast to intracardiac shuntswhere appearance of contrast in the left heart isdependent on the pressure gradient between the RAand LA and is thus respiratory dependent andphasic in appearance (Table 5) (49,50). Detectionof intrapulmonary shunts may also be improved byperforming contrast-enhanced echocardiography inthe standing position (51). Alternatively, techne-tium-99m–labeled macroaggregated albumin per-fusion scanning can be utilized to diagnose HPS.Under normal conditions, the majority of labeledalbumin is trapped within the pulmonary circula-tion. In the presence of intrapulmonary shunting,the albumin is not completely trapped in the lungs

iac Events

ensitivity Specificity PPV NPV

0.0% 96.2% 0.0% 86.4%

20.0% 90.5% 25.0% 87.7%

. †significant intraoperative cardiac event defined as elevation of cardiac troponin

Figure 7. DSE RevealiOutflow Tract Obstruc

At peak dobutamine, nthe late peaking dynamFigures 1 and 6. (See O

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quantified by its appearance in other organs, includ-ing the brain, liver, and spleen (49,50). Obviously,atrial septal defect needs to be excluded as it willalso result in isotope appearance in the liver. Pul-monary angiography is not commonly used for thediagnosis of HPS but allows for the direct visual-ization of intrapulmonary vascular malformations(49,50).

Figure 8. Saline Contrast Echocardiography Performed in a PatiPulmonary AVM

The upper left panel is immediately after appearance of contrast inand reveals nearly continuous flow into the LA and LV. The lower lequal contrast in both the right and left ventricles and the lower ricontinued appearance of contrast into the LV when contrast is dimother abbreviations as in Figure 1. (See Online Video 6.)

Table 5. Characteristics of Intrapulmonary Shunts andIntra-Cardiac Shunts on Saline Contrast Echocardiography

Shunt Type Contrast Appearance on Left Side of Heart

Intrapulmonary Dependent on time necessary fortranspulmonary blood flow;contrast visualized in pulmonary veins;continuous appearance;can appear after clearance of contrastfrom right side of heart

Intracardiac Dependent on interatrial pressure gradient;occurs when RAP exceeds LAP;respiratory dependent;phasic appearance

LA � left atrium; LAP � left atrial pressure; RA � right atrium; RAP � right

yatrial pressure.

Portopulmonary hypertension. Portopulmonary hy-pertension (PPH) is a form of pulmonary arterialhypertension associated with portal hypertensionwith or without accompanying cirrhosis (52,53).PPH is hypothesized to occur: 1) as a result ofincreased vascular wall shear stress resulting inendothelial dysfunction; and 2) due to the porto-systemic shunting of vasoactive substances from thesplanchnic circulation to the pulmonary circulation,leading to progressive pulmonary vascular vasocon-striction and remodeling (52,53). Hemodynami-cally, the diagnostic criteria for PPH includes a meanpulmonary artery pressure (mPAP) �25 mm Hg at rest,mean pulmonary capillary wedge pressure �15 mm Hg,and pulmonary vascular resistance �240 dynes/s/cm–5 (50,53). Risk factors for the development of

PH include female sex and autoimmune hepatitis,hile ESLD secondary to hepatitis C is associatedith a decreased risk of PPH (54). Clinically,atients with PPH are asymptomatic for months to

With ESLD Revealing Marked Right-to-Left Shunt Through

ht heart. The upper right panel is 5 beats following appearanceanel is approximately 10 s after injection of contrast and revealspanel is recorded 15 s following injection of contrast and revealsing in the right ventricle. AVM � arteriovenous malformation;

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syncope, and chest pain later in the disease course(49,53). Small studies have demonstrated thatpre-operative mPAP �35 mm Hg is associatedwith no significant increased mortality, pre-operative mPAP between 35 and 50 mm Hg isassociated with a 50% mortality, and pre-operative mPAP �50 mm Hg is associated with

ortality approaching 100% after LT (55). Manyransplant centers consider PPH with a pre-perative mPAP �50 mm Hg a contraindicationo LT due to the increased risk, uncontrollablentraoperative bleeding, and reduced transplantrgan perfusion post-transplantation (56).The AASLD and the AHA/ACCF recommend

creening for elevated pulmonary pressures in allT candidates with Doppler echocardiography

24,40) (Fig. 9; Online Video 7). Utilizing the peakricuspid regurgitant velocity (TRV), the estimatedA pressure (RAP), and the modified Bernoulli

ld Man With PPH Related to ESLD

er view reveals a markedly dilated right ventricle and righttricuspid regurgitation. B: Continuous wave Doppler documents aetween the right ventricle and the right atrium consistent withertension. PPH � portopulmonary hypertension; other abbrevia-e Online Video 7.)

quation, the RV systolic pressure (RVSP) can bealculated as: 4(TRV)2 � RAP (49,52). In the

absence of pulmonic stenosis, the pulmonary sys-tolic pressure is equivalent to the RVSP. In LTcandidates undergoing screening for PPH, TTEhas a sensitivity of 97% and a specificity of 77% fordiagnosing elevated pulmonary pressures (57).These pressures must be interpreted carefully as upto 20% of LT candidates show moderately in-creased pulmonary pressures attributable to thehyperdynamic state of cirrhotic cardiomyopathy,volume overload, or LV dysfunction (53,58), whileonly 5% to 10% of LT candidates have elevatedpulmonary pressures due to PPH (59). This distinc-tion is critical as patients with elevated pulmonarypressures for etiologies other than PPH do not havean increased rate of adverse events with LT (58).The AASLD and AHA/ACCF recommend rightheart catheterization with calculation of pulmonaryvascular resistance for confirming the diagnosis ofPPH when an RVSP of 45 to 60 mm Hg is found(24,40). Recent case series and retrospective analy-ses have shown that successful LT can be facilitatedin patients after reduction in pulmonary pressureswith pharmacotherapy (55,60).Pericardial effusions. LT candidates characteristi-ally have fluid retention, manifest as a combinationf peripheral edema, ascites, pleural effusions, andericardial effusion (55,60). Pericardial effusions areeported in up to 63% of patients with ESLD, butre typically small in size and hemodynamically wellolerated (61). While the evaluation of a pericardialffusion should include determination of the size,ircumferential extent, and presence or absence ofemodynamic compromise, the development ofardiac tamponade in the LT candidate is rare andas been reported only in isolated case reports61,62).Patent foramen ovale. Patent foramen ovale (PFO)is present in a quarter of the general population, andtypically portends a benign course (63). Contrast-enhanced echocardiography or color Doppler im-aging is recommended for the diagnosis of PFO. Inthe setting of LT, spontaneous echogenic contrastmaterial representing air and/or microthrombi isseen in the right heart of all patients at the time ofdonor liver reperfusion (64). Hypothetically,changes in intracardiac pressure during the periop-erative period can result in paradoxical emboli.Some studies have reported an increased risk ofembolic events in patients with a PFO during LT

Figure 9. A 57-Year-O

(A) The apical 4-chambatrium and moderate106-mm Hg gradient bsevere pulmonary hyption as in Figure 1. (Se

(64), while a more recent retrospective study found



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no significant difference in outcomes for patientswith a PFO (65).

Assessing Risk of Specific Procedures

Risk of transjugular intrahepatic portosystemic shuntprocedure. Insertion of a transjugular intrahepatic

ortosystemic shunt (TIPS) is standard treatmentor refractory ascites and uncontrolled varicealleeding (7,9,66,67). Placement of a TIPS results inn abrupt increase in cardiac preload due to a shiftf portal venous blood into the systemic circulation,eading to an additional increase in cardiac output,ncreased LV and RV end-diastolic volumes, andurther decrease in systemic vascular resistance (4).hese acute hemodynamic effects in the setting of

irrhotic cardiomyopathy can result in high-outputongestive heart failure, cardiac arrhythmias, andyocardial ischemia (4). In a study comparing

utcomes of TIPS to repeated large-volume para-entesis, Ginès et al. (68) found that 12% of theIPS group developed heart failure as compared

o none in the paracentesis group. Similarly,chwartz et al. (69) found that 13% of patientseveloped heart failure after TIPS placement.ore recently, Cazzaniga et al. (67) reported that

he presence of diastolic dysfunction (defined as/A ratio �1) 4 weeks post-TIPS was the only

independent predictor of overall survival follow-ing the procedure. Rabie et al. (66) revealed thatthe presence of diastolic dysfunction in the pre-TIPS period predisposed patients to both cardiacand noncardiac death post-procedure. Giventhese findings, it has been suggested that afterTIPS insertion, patients with evidence of dia-stolic dysfunction should be preferentially con-

Figure 10. Serial Echocardiograms in a Patient With Acute Decom

End systolic apical 4-chamber view recorded 24 h after an otherwissevere systolic dysfunction and clinical congestive heart failure (lefttion and there was full recovery of function 3 months later (right p

sidered for LT as compared to patients withnormal diastolic function (67).Acute effects of liver transplantation. LT imposesmmediate stress on the heart. Intraoperatively,here is impaired myocardial contractility with anbrupt increase in peripheral vascular resistance andsudden decrease in preload which can be further

xacerbated by hemorrhage, third space fluid losses,nd inadequate volume resuscitation, resulting ineduced cardiac output (4,8,9). Conversely aggres-ive fluid repletion or blood transfusion can result inolume overload and the development of pulmonarydema due to occult cardiac disease. Pulmonarydema occurs in 12% to 56% of LT candidates inhe perioperative period (9,25). Metabolic derange-ents related to post-reperfusion syndrome can

urther impair cardiac contractility. The stress ofT can thus unmask the latent systolic dysfunc-

ion of cirrhotic cardiomyopathy, leading to overteart failure (Fig. 10; Online Video 8) with heartailure and other cardiac complications account-ng for 7% to 21% of mortality following LT8,9). Unfortunately, there are no reliable diag-ostic criteria to identify LT candidates withirrhotic cardiomyopathy at risk of developingardiac complications in the perioperative period.im et al. (10) evaluated the use of DSE for

dentifying patients with cirrhotic cardiomyopa-hy and found a blunted DSE response (defineds �10% reduction in LV end-diastolic volume,20% decrease in end-systolic volume, and10% increase in LV ejection fraction) in 25% ofT candidates. However, the prognostic value ofblunted DSE in predicting perioperative com-

lications is unknown (4).

sation Following Liver Transplantation

ccessful liver transplant (LT) in a patient who developed acuteel). Pre-operative testing had revealed normal LV systolic func-l). Abbreviation as in Figure 1. (See Online Video 8.)

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Heart Diseases Causing Liver Disease

Occasionally, pre-operative evaluation of the LTcandidate reveals cardiac disease as the etiology ofESLD. This syndrome termed cardiac cirrhosis ischaracterized by chronic right heart failure leadingto elevated systemic venous pressures, passive he-patic venous congestion and subsequent sinusoidalcollagen deposition and eventual cirrhosis (4,49).Cardiovascular diseases that may result in cardiaccirrhosis include dilated cardiomyopathy with sec-ondary pulmonary hypertension, restrictive cardio-myopathy, constrictive pericarditis (Fig. 11; OnlineVideo 9), primary pulmonary hypertension, or mi-tral stenosis with secondary pulmonary hyperten-sion (4,49). The clinician should suspect cardiaccirrhosis when the triad of right heart failure,hepatomegaly, and ascites with a high proteincontent and high serum ascites albumin gradientis present (4,49). Ultimately, the combined use ofliver vein catheterization with liver tissue sam-pling and right heart catheterization can help todiscriminate between portal hypertension andright-sided heart failure (4). As the treatment ofcardiac cirrhosis is based on treatment of theunderlying cardiac disorder, there is no role forLT in this syndrome (49).

Recommendations

Cardiovascular complications account for consider-able mortality and morbidity associated with LT.The AASLD and the AHA recommend TTE forall LT candidates to evaluate cardiac chamber sizes,systolic and diastolic function, valvular function,and pulmonary artery pressure and to exclude thepresence of intracardiac shunts, significant LVOTO, orpericardial effusion (24,40). Additional noninvasiveunctional assessment for CAD is recommended forT candidates based on the presence of risk factors

24,40). The cardiac imaging modality of choice foroninvasive screening of CAD remains unclear. AsSE appears to be an effective screening test and

an provide a comprehensive cardiac assessment, its currently recommended by the AASLD (24).able 6 provides a summary of these recommenda-

ions based on the body of evidence reviewed. The rolef cardiac imaging in the evaluation of the LTandidate continues to be in evolution. Further studiesre necessary to develop an evidence-based approacho the diagnosis of underlying cardiac pathology (es-ecially CAD) and identify the subset of patients at
ncreased risk of cardiovascular complications.
Reprint requests and correspondence: Dr. William F.rmstrong, University of Michigan Medical Center,epartment of Internal Medicine, Division of Cardiol-

gy, Cardiovascular Center Floor 2 Room 2161, 1500ast Medical Center Drive SPC 5853, Ann Arbor,ichigan 48109-5853. E-mail: [email protected].

Figure 11. Two-Dimensional Echocardiogram Recorded in a56-Year-Old Man With ESLD Related to “CryptogenicCirrhosis”

Echocardiography at the time of transplant evaluation revealedclassic findings of pericardial constriction. In the apical 4-cham-ber view (A), note the rightward shift of the ventricular septum(arrows) in this inspiratory still frame. In the real-time image,the respiratory variation of septal position is better appreciated.Transmitral (B) and transtricuspid (C) Doppler confirm exagger-ated respiratory variation consistent with constriction. Abbrevia-tion as in Figure 1. (See Online Video 9.)

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Table 6. Pre-Operative Cardiovascular Assessment

Cardiovascular Finding Screening Recommendations Limitations/Considerations

Coronary artery disease DSE evaluation for all patients �50 yrs old, chronicsmokers, diabetes, family or clinical history of heartdisease

Low sensitivity and low NPV in some studies;frequent inability to reach target heart rate (studynondiagnostic);numerous proposed diagnostic algorithms;coronary angiography recommended forconfirmation of positive studies

Cirrhotic cardiomyopathy Echocardiography to assess systolic/diastolic function, LVH,cardiac chamber sizes

No diagnostic criteria available

LVOTO/HCM Echocardiography Diagnosis of HCM can be difficult in setting ofunderlying cirrhotic cardiomyopathy, LVOTO;intraoperative TEE monitoring to assess ventricularvolumes and dynamic LVOTO

Valvular heart disease Echocardiography Hyperdynamic circulatory state with high transvalvularflow can overestimate degree of valve stenosis

Portopulmonary hypertension Doppler echocardiography Inability to distinguish between pulmonary arterialhypertension and pulmonary venous hypertension;right heart catheterization recommended fordiagnosis confirmation

Hepatopulmonary syndrome Contrast echocardiography Must be differentiated from atrial septal defect andpatent foramen ovale

Pericardial effusion Echocardiography Assessment for cardiac tamponade; frequentreaccumulation due to underlying ESLD

Patent foramen ovale Contrast echocardiography Significance of diagnosis unclear; intraoperative TEEmonitoring for prevention of venous air emboli

HCM � hypertrophic cardiomyopathy; LVH � left-ventricular hypertrophy; LVOTO � left-ventricular outflow tract obstruction; TEE � transesophageal echocardiography.

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R E F E R E N C E S

1. Raval Z, Harinstein ME, Skaro AI, etal. Cardiovascular risk assessment ofthe liver transplant candidate. J AmColl Cardiol 2011;58:223–31.

2. Dec G, Kondo N, Farrell M, DienstagJ, Cosimi A, Semigran M. Cardiovas-cular complications following livertransplantation. Clin Transplant 1995;9:463–71.

3. Zardi EM, Abbate A, Zardi DM, etal. Cirrhotic cardiomyopathy. J AmColl Cardiol 2010;56:539–49.

4. Moller S, Dumcke CW, Krag A. Theheart and the liver. Expert Rev Gas-troenterol Hepatol 2009;3:51–64.

5. Møller S, Henriksen J. Cirrhotic car-diomyopathy: a pathophysiological re-view of circulatory dysfunction in liverdisease. Heart 2002;87:9–15.

6. Pozzi M, Carugo S, Boari G, et al.Evidence of functional and structuralcardiac abnormalities in cirrhotic pa-tients with and without ascites. Hepa-tology 1997;26:1131–7.

7. Baik SK, Fouad TR, Lee SS. Cir-rhotic cardiomyopathy. Orphanet JRare Dis 2007;2:15.

8. Lee RF, Glenn TK, Lee SS. Cardiacdysfunction in cirrhosis. Best PractRes Clin Gastroenterol 2007;21:125– 40.

9. Gaskari SA, Honar H, Lee SS. Ther-
apy insight: cirrhotic cardiomyopathy.
Nat Clin Pract Gastroenterol Hepatol2006;3:329–37.

0. Kim MY, Baik SK, Won CS, et al.Dobutamine stress echocardiographyfor evaluating cirrhotic cardiomyopa-thy in liver cirrhosis. Korean J Hepatol2010;16:376–82.

1. Abd-El-Aziz TA, Abdou M, FathyA, Wafaie M. Evaluation of CardiacFunction in Patients with Liver Cir-rhosis. Intern Med 2010;49:2547–52.

2. Finucci G, Desideri A, Sacerdoti D, etal. Left ventricular diastolic functionin liver cirrhosis. Scand J Gastroen-terol 1996;31:279–84.

3. Torregrosa M, Aguadé S, Dos L, et al.Cardiac alterations in cirrhosis: revers-ibility after liver transplantation.J Hepatol 2005;42:68–74.

4. Ortiz-Olvera NX, Castellanos-Pallares G, Gomez-Jimenez LM, etal. Anatomical cardiac alterations inliver cirrhosis: an autopsy study. AnnHepatol 2011;10:321–6.

5. Ehtisham J, Altieri M, Salamé E,Saloux E, Ollivier I, Hamon M. Cor-onary artery disease in orthotopic livertransplantation: pretransplant assess-ment and management. Liver Transpl2010;16:550–7.

6. Keeffe BG, Valantine H, Keeffe EB.Detection and treatment of coronaryartery disease in liver transplant candi-
dates. Liver Transpl 2001;7:755–61.
17. Carey WD, Dumot JA, Pimentel RR,et al. The prevalence of coronary ar-tery disease in liver transplant candi-dates over age 50. Transplantation1995;59:859–64.

18. Tiukinhoy-Laing SD, Rossi JS, Bay-ram M, et al. Cardiac hemodynamicand coronary angiographic character-istics of patients being evaluated forliver transplantation. Am J Cardiol2006;98:178–81.

19. Patel S, Kiefer TL, Ahmed A, et al.Comparison of the frequency of coro-nary artery disease in alcohol-relatedversus non-alcohol-related endstageliver disease. Am J Cardiol 2011;108:1552–5.

20. Plotkin JS, Scott VL, Pinna A,Dobsch BP, De Wolf AM, Kang Y.Morbidity and mortality in patientswith coronary artery disease under-going orthotopic liver transplanta-tion. Liver Transpl Surg 1996;2:426 –30.

21. Vogt DP, Henderson JM, CareyWD, Barnes D. The long-term sur-vival and causes of death in patientswho survive at least 1 year after livertransplantation. Surgery 2002;132:775– 81.

22. Pruthi J, Medkiff KA, Esrason KT, etal. Analysis of causes of death in livertransplant recipients who survivedmore than 3 years. Liver Transpl
2001;7:811–5.

2

2

2

2

2

2

3

3

3

3

3

3

3

3

3

3

4

4

4

4

4

4


J A N U A R Y 2 0 1 3 : 1 0 5 – 1 9

Garg and Armstrong


118

23. Diedrich D, Findlay J, Harrison B,Rosen C. Influence of coronary arterydisease on outcomes after liver trans-plantation. Transplant Proc 2008;40:3554–7.

4. Murray KF, Carithers Jr RL. AASLDpractice guidelines: evaluation of thepatient for liver transplantation.Hepatology 2005;41:1407–32.

5. Donovan CL, Marcovitz PA, PunchJD, et al. Two-dimensional and dobut-amine stress echocardiography in thepreoperative assessment of patients withend-stage liver disease prior to ortho-topic liver transplantation. Transplanta-tion 1996;61:1180–8.

6. Plotkin JS, Benitez RM, Kuo PC, etal. Dobutamine stress echocardiogra-phy for preoperative cardiac risk strat-ification in patients undergoing ortho-topic liver transplantation. LiverTranspl Surg 1998;4:253–7.

7. Harinstein M, Flaherty J, Ansari A, etal. Predictive value of dobutaminestress echocardiography for coronaryartery disease detection in liver trans-plant candidates. Am J Transplant2008;8:1523–8.

8. Umphrey LG, Hurst RT, Eleid MF,et al. Preoperative dobutamine stressechocardiographic findings and subse-quent short-term adverse cardiac eventsafter orthotopic liver transplantation.Liver Transpl 2008;14:886–92.

9. Williams K, Lewis JF, Davis G,Geiser EA. Dobutamine stress echo-cardiography in patients undergoingliver transplantation evaluation. Trans-plantation 2000;69:2354–6.

0. Findlay J, Keegan M, Pellikka P,Rosen C, Plevak D. Preoperative do-butamine stress echocardiography, in-traoperative events, and intraoperativemyocardial injury in liver transplantation.Transplant Proc 2005;37:2209–13.

1. Davidson CJ, Gheorghiade M, Fla-herty JD, et al. Predictive value ofstress myocardial perfusion imaging inliver transplant candidates. Am J Car-diol 2002;89:359–60.

2. Aydinalp A, Bal U, Atar I, et al. Valueof stress myocardial perfusion scan-ning in diagnosis of severe coronaryartery disease in liver transplantationcandidates. Transplant Proc 2009;41:3757–60.

3. Zoghbi GJ, Patel AD, Ershadi RE,Heo J, Bynon JS, Iskandrian AE.Usefulness of preoperative stress per-fusion imaging in predicting prognosisafter liver transplantation. Am J Car-diol 2003;92:1066–71.

4. Bradley SM, Soine LA, Caldwell JH,Goldberg SL. Screening stress myo-cardial perfusion imaging and eligibil-ity for liver transplantation. Am J
Cardiol 2010;105:1010–3.
5. Pletcher MJ, Tice JA, Pignone M,Browner WS. Using the coronary ar-tery calcium score to predict coronaryheart disease events: a systematic re-view and meta-analysis. Arch InternMed 2004;164:1285–92.

6. McAvoy NC, Kochar N, McKillop G,Newby DE, Hayes PC. Prevalence ofcoronary artery calcification in pa-tients undergoing assessment for or-thotopic liver transplantation. LiverTranspl 2008;14:1725–31.

7. Appleton CP, Hurst RT. Reducingcoronary artery disease events in livertransplant patients: moving towardidentifying the vulnerable patient.Liver Transpl 2008;14:1691–3.

8. Keeling AN, Flaherty JD, Davarpa-nah AH, et al. Coronary multidetectorcomputed tomographic angiographyto evaluate coronary artery disease inliver transplant candidates: methods,feasibility and initial experience.J Cardiovasc Med 2011;12:460–8.

9. Cassagneau P, Jacquier A, Giorgi R,et al. Prognostic value of preopera-tive coronary computed tomographyangiography in patients treated byorthotopic liver transplantation. EurJ Gastroenterol Hepatol 2012;24:558 – 62.

0. Lentine KL, Costa SP, Weir MR, etal. Cardiac disease evaluation andmanagement among kidney and livertransplantation candidates a scientificstatement from the American HeartAssociation and the American Collegeof Cardiology Foundation. Circula-tion 2012;126:617–63.

1. Maraj S, Jacobs LE, Maraj R, et al.Inducible left ventricular outflow tractgradient during dobutamine stressechocardiography: an association withintraoperative hypotension but not acontraindication to liver transplanta-tion. Echocardiography 2004;21:681–5.

2. Harley I, Jones E, Liu G, McCall P,McNicol P. Orthotopic liver trans-plantation in two patients with hyper-trophic obstructive cardiomyopathy.Br J Anaesth 1996;77:675–7.

3. Lim YC, Doblar DD, Frenette L, FanPH, Poplawski S, Nanda NC. Intra-operative transesophageal echocardi-ography in orthotopic liver transplan-tation in a patient with hypertrophiccardiomyopathy. J Clin Anesth 1995;7:245–9.

4. Alper I, Ulukaya S, Demir F, Kilic M.Effects of cardiac valve dysfunction onperioperative management of livertransplantation. Transplant Proc2009;41:1722–6.

5. Pollard RJ, Sidi A, Gibby GL, LobatoEB, Gabrielli A. Aortic stenosis with
end-stage liver disease: prioritizing
surgical and anesthetic therapies.J Clin Anesth 1998;10:253–61.

46. Adachi T, Murakawa M, Uetsuki N,Segawa H. Living related donor livertransplantation in a patient with se-vere aortic stenosis. Br J Anaesth1999;83:488–90.

47. Martı́nez G, Barbera J, Visa J, et al.Hepatopulmonary syndrome in candi-dates for liver transplantation. J Hepa-tol 2001;34:651–7.

48. Taur P, Balust J, Zavala E, Garcia-Valdecasas J. Liver transplantation inhigh-risk patients: hepatopulmonarysyndrome and portopulmonary hyper-tension. Transplant Proc 2005;37:3861–4.

49. Naschitz JE, Slobodin G, Lewis RJ,Zuckerman E, Yeshurun D. Heartdiseases affecting the liver and liverdiseases affecting the heart. AmHeart J 2000;140:111–20.

50. Hoeper MM, Krowka MJ, StrassburgCP. Portopulmonary hypertensionand hepatopulmonary syndrome.Lancet 2004;363:1461–8.

51. Lenci I, Alvior A, Manzia TM, TotiL, Neuberger J, Steeds R. Saline con-trast echocardiography in patientswith hepatopulmonary syndromeawaiting liver transplantation. J AmSoc Echocardiogr 2009;22:89–94.

52. Ramsay M. Portopulmonary hyper-tension and right heart failure in pa-tients with cirrhosis. Curr Opin An-aesthesiol 2010;23:145–50.

53. Porres-Aguilar M, Zuckerman MJ,Figueroa-Casas JB, Krowka MJ. Por-topulmonary hypertension: state ofthe art. Ann Hepatol 2008;7:321–30.

54. Kawut SM, Krowka MJ, Trotter JF, etal. Clinical risk factors for portopul-monary hypertension. Hepatology2008;48:196–203.

55. Swanson K, Wiesner R, Nyberg S,Rosen C, Krowka M. Survival in por-topulmonary hypertension: MayoClinic experience categorized by treat-ment subgroups. Am J Transplant2008;8:2445–53.

56. Krowka MJ, Mandell MS, RamsayMAE, et al. Hepatopulmonary syn-drome and portopulmonary hyperten-sion: a report of the multicenter livertransplant database. Liver Transpl2004;10:174–82.

57. Kim W, Krowka MJ, Plevak DJ, et al.Accuracy of Doppler echocardiogra-phy in the assessment of pulmonaryhypertension in liver transplant candi-dates. Liver Transpl 2000;6:453–8.

58. Castro M, Krowka MJ, SchroederDR, et al. Frequency and clinicalimplications of increased pulmonaryartery pressures in liver transplantpatients. Mayo Clin Proc 1996;71:
543–51.

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6

6

6

6

6

6

6

6

6

etr


J A N U A R Y 2 0 1 3 : 1 0 5 – 1 9

Garg and Armstrong


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59. Kuo PC, Plotkin JS, Gaine S, et al.Portopulmonary hypertension and theliver transplant candidate. Transplan-tation 1999;67:1087–93.

0. Sussman N, Kaza V, Barshes N, et al.Successful liver transplantation fol-lowing medical management of por-topulmonary hypertension: a single-center series. Am J Transplant 2006;6:2177–82.

1. Cheung TK, Tam W, BartholomeuszD, Harley H, Johnson R. Hepatichydropericardium. J GastroenterolHepatol 2004;19:109–12.

2. Akinci SB, Gaine SP, Post W, MerritWT, Tan HP, Winters B. Cardiactamponade in an orthotopic liver re-cipient with pulmonary hypertension.Crit Care Med 2002;30:699–701.

3. Meissner I, Whisnant JP, KhandheriaBK, et al. Prevalence of potential riskfactors for stroke assessed by trans-esophageal echocardiography and ca-
rotid ultrasonography: the SPARC
study. Stroke prevention: assessmentof risk in a community. Mayo ClinProc 1999;74:862–9.

4. Ellis JE, Lichtor JL, Feinstein SB, etal. Right heart dysfunction, pulmo-nary embolism, and paradoxical em-bolization during liver transplantation.Anesth Analg 1989;68:777–82.

5. Alba AC, Verocai Flaman F, GrantonJ, Delgado D. Patent foramen ovaledoes not have a negative impact onearly outcomes in patients undergoingliver transplantation. Clin Transplant2011;25:151–5.

6. Rabie RN, Cazzaniga M, Salerno F,Wong F. The use of E/A ratio as apredictor of outcome in cirrhotic pa-tients treated with transjugular intra-hepatic portosystemic shunt. Am JGastroenterol 2009;104:2458–66.

7. Cazzaniga M, Salerno F, Pagnozzi G,et al. Diastolic dysfunction is associ-ated with poor survival in patients
with cirrhosis with transjugular intra-
hepatic portosystemic shunt. Gut2007;56:869–75.

8. Ginès P, Uriz J, Calahorra B, et al.Transjugular intrahepatic portosys-temic shunting versus paracentesisplus albumin for refractory ascites incirrhosis. Gastroenterology 2002;123:1839–47.

9. Schwartz JM, Beymer C, Althaus SJ,et al. Cardiopulmonary consequencesof transjugular intrahepatic portosys-temic shunts: role of increased pulmo-nary artery pressure. J Clin Gastroen-terol 2004;38:590–4.

Key Words: cirrhosis ychocardiography y liverransplantation y pre-operativeisk assessment.

A P P E N D I X

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Echocardiography in Liver Transplant Candidates