rePrevention and treatme

AssB.C, An

Torona M5GTorona M5GToronG 2C

* Corresponding author. Tel.: 1 416 340 4800x6443; Fax: 1 416 340 3698.E-mail addresses: massimiliano.meineri@uhn.ca (M. Meineri), adriaan.vanrensburg@uhn.ca (A.E. Van Rensburg), annette.

vegas@uhn.ca (A. Vegas).d Tel.: 416 340 4800x5877; Fax: 416 340 3698.e Tel.: 416 340 4800x8727; Fax: 416 340 3698.

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Best Practice & Research ClinicalAnaesthesiology

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Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229Keywords:heart Failure/physiopathology/*therapyheart-assist devices/*adverse effectshaemodynamicsrisk assessmentrisk factorstreatment outcomeventricular dysfunctionright/*aetiology/physiopathology/therapy*ventricular function, left*ventricular function, right

Right ventricular failure (RVF) complicates 2050% of leftventricular assist device (LVAD) implantation cases and contrib-utes to increased postoperative morbidity and mortality. NormalLVAD function alters the highly compliant right ventricular (RV)physiology, which may unmask RVF. Risk scores for predicting RVFpost-LVAD incorporate multiple risk factors but have not beenprospectively validated. Prevention of RVF consists of optimisingRV function by modifying RV preload and afterload, providingadequate intra-operative RV protection and minimising bloodtransfusions. Treatment of RVF relies on inotropic support,decreasing pulmonary vascular resistance and adjusting LVADows to minimise distortion of RV geometry. RVAD insertion isa last recourse when RVF is refractory to medical treatment.

2012 Elsevier Ltd. All rights reserved.Elizabeth Street, EN 3, Toronto, ON, Canada M5Massimiliano Meineri, MD,Adriaan E. Van Rensburg, MProfessor of Anaesthesia b,e

of Anaesthesia c,*aUniversity of Toronto, Staff Anaesthesiologist,Elizabeth Street, EN 3-442, Toronto, ON, CanadbUniversity of Toronto, Staff Anaesthesiologist,Elizabeth Street, EN 3-443, Toronto, ON, CanadcUniversity of Toronto, Staff Anaesthesiologist,1521-6896/$ see front matter 2012 Elsevier Ltdoi:10.1016/j.bpa.2012.03.006nt

istant Professor of Anaesthesia a,d,hB, MMED, FCA[SA], FRCPC, Assistantnette Vegas, MD, FRCPC, Associate Professor

to General Hospital, Department of Anaesthesia and Pain Management, 2002C4

to General Hospital, Department of Anaesthesia and Pain Management, 2002C4

to General Hospital, Department of Anesthesia and Pain Management, 2004Right ventricular failu after LVAD implantation:9d. All rights reserved.

Introduction

The treatment of refractory heart failure with ventricular assist devices (VADs) has become anestablished practice with acceptable results as either a destination therapy (DT) or a bridge-to-transplant (BTT) therapy. Technological developments have led to the use of non-pulsatile contin-uous-ow devices with superior overall results compared with the original pulsatile devices.13

Some degree of right ventricular dysfunction (RVD) is common in patients presenting for leftventricular assist device (LVAD) surgery. The incidence of overt right ventricular failure (RVF) post-LVAD implantation has been reported between 20% and 50%18 and remains unchanged despite animproved immediate postoperative mortality9 with newer generations of LVADs.6,10,11 Early RVF post-

M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229218LVAD is associated with increased operative mortality, postoperative morbidity, mortality, intensivecare unit (ICU) and hospital length of stay.4,7,12 The development of RVF shortens survival even aftersuccessful heart transplantation in BTT LVAD patients.13

The diagnosis of RVF post-LVAD implantation is complex. Most studies46,14,15 have used a combi-nation of management criteria to dene RVF, confounding comparisons between trials. This articlereviews basic right ventricular physiology and pathophysiology before and after LVAD implantation, aswell as management strategies for RVF in this complex clinical situation.

Physiology and pathophysiology of RV function

Normal

The right ventricle (RV) is structurally and mechanically distinct from the left ventricle (LV) andresponds differently to diseased states (Table 1). Anatomically the RV is a complex three-dimensionalstructure that forms the most anterior part of the heart lying directly beneath the sternum.16 In sagittalsection it appears triangular and is crescent shaped in cross section with the interventricular septum(IVS) concave towards the LV (Fig. 1). RV shape and function are signicantly inuenced by the positionof the IVS, which becomes a prominent factor when either ventricle is affected by abnormal loadingconditions. The RV and LV are connected in series: the output of one ventricle is the input for the other.

Contraction of the highly compliant thin-walled RV is a sequential process starting at the inlet, thenfree wall and ending at the infundibulum (or RV outow tract). Under normal conditions, the RV iscoupled to the highly compliant pulmonary vascular system, which renders it a volume pump (lowpressure) rather than a pressure pump. During the cardiac cycle, the RV pumps an equal stroke volume(SV) as the LV, but at 25% of the strokework.17 The RV has a greater end-diastolic volume than the LV, sothe RV ejection fraction is less (RVEF 4045%) than the LV (LVEF 5055%).18 There is an inverse rela-tionship between RVEF and pulmonary artery pressure (PAP). The RV is more sensitive to an afterloadchange compared to the LV. A similar increase in afterload to the RV (PAP) and LV (aortic pressure) leadsto a signicantly greater decrease in SV for the RV compared to the LV.19 In contrast, the RV toleratesand adapts more easily to volume (diastolic) overload.

Normal RV perfusion occurs during both systole and diastole. Lower stroke work and wall stressensure that the RV has lower resting coronary blood ow (0.40.7 ml min1 g1 of myocardium) andoxygen extraction (50% vs. 75%) compared with the LV.19 This ow and extraction reserve make the RVmore resilient to ischaemia.

Table 1Normal RV and LV parameters.

Right ventricle Left ventricle

EDV, ml/m2 75 13 [49100] 65 12 [4490]Mass, g/m2 26 5 [1734] 87 12 [64110]Wall thickness, mm 25 711Ventricular pressure, mmHg 25/4 [[1530]/[17]] 130/8 [[90140]/[512]]Ventricular elastance, mmHg/ml 1.30 0.84 5.48 1.23PVR versus SVR, dyn s cm5 70 [20130] 1100 [7001600]Ejection fraction, % 4045 5055EDV, end-diastolic volume; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance.

Fig. 1. RV size and Function. Two perpendicular sections of a 3D TEE reconstruction of the right ventricle from tricuspid valve [TV] topulmonary [PV] valve are shown. The cross section [A] demonstrates the crescent shape and the sagittal section [B] the triangularshape of the RV. Ventricular interdependence between the left ventricle [LV] and RV during systole relies on interventricular septum

M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229 219Ventricular interdependence implies that the shape, size and compliance of one ventricle affect thesize, shape and pressurevolume relationship of the other through direct mechanical interactions.16,19

Systolic interdependence is mediated primarily through the IVS, while diastolic interdependenceoccurs mainly via the pericardium. Ventricular interdependence becomes an important factor whenone of the ventricles is exposed to altered loading conditions (Fig. 1).

Heart failure

Left heart failure canaffect theRV throughmultiplemechanisms.Pulmonaryhypertension is a commoncomplication of both systolic and diastolic left heart failure, which incites the initial adaptive response ofRV hypertrophy.15 Over a short time, progressive contractile dysfunction is followed by RV dilatation toincrease preload and maintain cardiac output (CO). Clinically this manifests as rising lling pressures,decrease in CO andworsening tricuspid regurgitation (TR) frompoor leaet coaptation. RVF causes hepaticvenous hypertension, which contributes to hepatic hypoxia and persisting liver dysfunction.

In heart failure patients, an elevated PAP >39 mmHg and the presence of RV dysfunction arepowerful independent predictors of mortality. As the RV fails, the typical inverse relationship of RVEFand PAP is lost. Low PAPs in the setting of RVF are in fact associated with reduced patient survival.

The same cardiomyopathic process that affects the LV can also involve the RV. Interventricular septaldysfunction and coronary ischaemia fromeither coronaryartery diseaseor decreased perfusion bya failingLVmaynegativelyaffect theRV.Diastolic RV function canbe impairedbyadilated LV in a limitedpericardialspace.17 Preoperative LV dysfunction may mask underlying RV dysfunction as RV preload is limited.

Post-LVAD implantation

LVAD function has an unpredictable effect on RV function (Fig. 2). Successful lling of the LVADrequires the native RV to increase its output to match LVAD ow. Augmentation of CO and systemic

position as shown in cross section for different clinical scenarios.

blood ow by the LVAD increase venous return to the RV. To cope with the increased preload, RVdiastolic compliance improves through decreased RV afterload and leftward IVS shift as the LVADreduces LV pressure. RV efciency is maintained as the unloaded RV does not need to contract asvigorously to eject the increased RV preload.6,15,20,21 Clinically, this shows as a decrease in pulmonarycapillary wedge pressure (PCWP), PAP and peak RV systolic pressure (RVSP), which are conrmed byLVAD experimental models (Fig. 2).

Despite the favourable effects of reduced RV afterload, the RV may become mechanically disad-vantaged. RV pressure is related to free wall contraction and the position of the IVS. Global RV

Fig. 2. Heart failure and LVAD Physiology. Ao, aorta; CO cardiac output; CVP, central venous pressure; LAP, left atrial pressure; LVAD,left ventricular assist device; LVEDP, left ventricular end diastolic pressure; LVEDV, left ventricular end diastolic volume; MR, mitralregurgitation; TR, tricuspid regurgitation; PA, pulmonary artery; PCWP, pulmonary capillary wedge pressure; RAP, right atrialpressure; RVEDP, right ventricular end diastolic pressure; RVEDV, right ventricular end diastolic volume.

M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229220contractility may be impaired during LVAD support from changes in the IVS position and motion(Fig. 1). When the LV is severely unloaded, the IVS will bulge signicantly into the LV, jeopardisingefcient RV contraction. The RV free wall must work harder and cannot compensate for the loss ofseptal function causing fatigue, which further exhausts the RV. Maintaining normal septal position andfunction can compensate for the loss of RV free wall function.

A concern with continuous LV unloading by newer non-pulsatile devices is their potential negativeeffect on RV function by consistently altering IVS position. However, Patel et al.6 found no difference inRVD between pulsatile and continuous-ow LVADs.

LVAD implantation produces an inconsistent change in perioperative TR. Worsening of TR mayresult from a leftward shift in the IVS, increased pulmonary vascular resistance (PVR) from cardio-pulmonary bypass (CPB), systemic inammatory response syndrome (SIRS), transfusion and increasedpreload. High LVAD ows may distort the tricuspid valve (TV) annulus.

Interestingly, explanted pulsatile LVAD-supported hearts have shown less RV structural remodel-ling than the LV unless the RV was also supported by an RVAD.22

Assessment of RV function

Structure and function

Right heart assessment denes RV structure, determines function and identies potential reversiblecauses of dysfunction. Evaluation of the RV is challenging due to its anterior retrosternal position,complex geometry, poor endocardial border denition and the marked load dependence of haemo-dynamic indices.

Echocardiography is the most commonly used modality for RV evaluation, although cardiacmagnetic resonance imaging (MRI) has become the gold standard. There is good correlation betweencardiac MRI and computed tomography (CT) providing alternative modalities for RV evaluation23

during workup for LVAD insertion.Assessment of RV structure includes an evaluation of RV shape, size, volume and wall thickness.24

Three-dimensional echocardiography (Fig. 1) is a promising modality that could lead to a moreaccurate evaluation; however, MRI is still considered the most reliable method for measuring RVvolume.25,26 RVEF (normal 4076%)16 and RV fractional area change (RVFAC) (normal >40%) can becalculated from size and volume measurements obtained by any of these modalities.

Tricuspid valve annular plane systolic excursion (TAPSE) is an echocardiographic MModemeasurement of the lateral TV annulus longitudinal displacement during systole. A value of >15 mmdisplacement is a normal quantitative measure of RV systolic function. It is, however, less reliable inpatients with regional RV dysfunction since it only measures the lateral free wall longitudinal move-ment. Assessment of the TV annulus size, the presence and severity of TR, inferior vena cava size andhepatic venous blood ow pattern should also be part of routine RV evaluation. Despite relatively goodcorrelation among TAPSE, RVFAC and RVEF,16 most echocardiographers use a subjective eyeballassessment classifying global RV function as good, mild, moderate or severely reduced.

Post-LVAD implantation

Echocardiography remains the primary imaging modality for monitoring cardiac function in LVADpatients,26 asMRI is no longer an option but cardiac CT is a reliable alternative toMRI.27 Relative changein RV size and the degree of TR from an established baseline is serially followed with worsening RVfunction suggested by increased RV size and TR.

A decrease in TAPSE has been described15 post-LVAD placement from reduced RV afterload and theRV contractile requirement to sustain CO. However, a low TAPSE in conjunctionwith increasing RV sizeand TR supports worsening RV function.28

A key structural feature to evaluate is the IVS position, as abnormal motion towards one side or theother determines LV and RV shape. Septal changes might be suggestive of RV dysfunction, abnormalloading conditions, incorrect LVAD settings/placement or LVAD device failure. The pericardial spaceshould be examined for possible right heart compression by uid collections or thrombus.

During continuous-ow LVAD support, pre-existing RVD does not worsen in the intermediatemedian follow-up of 4.5 months. Moreover, the dimensions of the right-sided cardiac chambers werereduced in parallel with changes in the left-sided chambers. The RV response, however, appeared to bevariable.

Denition and predictors of RV failure

Denition RVF

Patients presenting for LVAD surgerymay demonstrate a broad clinical spectrum of preoperative RVdysfunction from being relatively asymptomatic to fulminant RVF. In this patient population, RVF isdened as a clinical syndrome that impairs the ability of the right heart to ll and eject appropriately orthe inability of the RV to provide adequate blood ow through the pulmonary circulation at a normalcentral venous pressure (CVP).29

Due to the retrospective nature of most studies, there is a lack of a universal denition for RVF post-LVAD among authors. RVF occurs when transpulmonary ow is unable to ll the LVAD despitemaximalmedical therapy. RVAD implant is unequivocally accepted as an extreme sign of RVF. Nevertheless, RVFnot requiring RVAD is variously dened, directly as haemodynamic derangement, indirectly as a needfor pharmacological support (inotropes or pulmonary vasodilators for>14 days) or as a combination ofthe two (Table 2).47,12,14,30

Potapov et al.11 usedmore specic haemodynamic and inotropic support criteria to institute inhalednitric oxide (iNO) to manage RVF (Table 3). This proposed haemodynamic denition of RVF has only

10,11

M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229 221been used by a few authors.

M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229222Risk factors

Table 2General criteria for RVF post-LVAD.

RVAD implantation or RV mechanical support [ECMO] Inotropic support for > 14 days, and/or started 14 days after LVAD implantation Pulmonary vasodilators [iNO] administered for > 214 days post-LVAD implantation Hospital discharge on inotropes

ECMO, extra-corporeal membrane oxygenator; iNO, inhaled nitric oxide; LVAD, left ventricular assist device; RVAD, rightventricular assist device; RV, right ventricle.

Table 3Criteria for iNO to manage RVF.

Inability to wean from cardiopulmonary bypass (CPB) Any 2 of the following sustained for > 15 min after separation from CPB:

B Mean arterial pressure 55 mmHgB Central venous pressure 16 mmHgB Mixed venous saturation 55%

Administration of more than 20 inotropic equivalents (IE)

B 10 mg/kg/min dopamine, dobutamine, enoximone or amrinone 10 IEB 0.1 mg/kg/min epinephrine or norepinephrine 15 IEB 1.0 mg/kg/min milrinone 15 IEB 0.1U/min vasopressin 10 IE

LVAD pump ow rate index 2.0 l/min2 calculated as LVAD ow divided by body surface area.Many authors have attempted to identify preoperative risk factors and develop risk scores to betteridentify LVAD candidates at risk for postoperative RVF and plan treatment. These at-risk patients maybenet from preoperative optimisation of right heart function or planned biventricular assist device(BiVAD) support. However, because of its multifactorial nature postoperative RV dysfunction remainsdifcult to predict in individual potential LVAD candidates.

Studies have identied both patient characteristics and haemodynamic parameters as altering risk.However, most studies are limited by small sample size, single institution, retrospective nature and theuse of different VADs within the same study.

Preoperative risk factors for post-LVAD RVF include patients characteristics (female gender andnon-ischaemic cardiomyopathy33), preoperative need for support (mechanical ventilation,4,5,13,30

mechanical circulatory support5,30 or intra-aortic balloon pump (IABP)6) haemodynamic parameters,biochemical markers and echocardiographic measurements (Table 4).

Haemodynamic parameters that may identify a vulnerable RV include increased preoperative4 orintra-operative12 CVP and a decreased RV stroke work index4,5,31 (RVSWI

Table 4Risk factors for RVF post-LVAD studies.

Author, year N LVAD RVF denition Risk factors

Ochiai,30 2002 245 HM I RVAD Mechanical Support, Female GenderNovacor

Dang, 2005 108 HM I Inotropes >14 days, RVAD Intraop [ CVP, Y PAP, Y MAP, ReoperationSantambrogio,13

200654 Novacor MAP 14 days,

RVADIABP

HM IIFitzpatrick,8

2008266 Multiple

devicesRVAD CI < 2.2 l/min/m2, RVSWI < 250, [ Cr, Previous

heart surgeryMatthews,5 2008 197 Multiple

devicesInotropes/vasodilators >14 days,RVAD

Mech Ventilation, Mechanical Support, PreopInotropes, Y CI, Y RVSWI, [ Cr, [ AST

Puwanant,28

200835 HM XVE Inotropes/vasodilators >14 days,

RVADTricuspid annular motion < 7.5 mm

HM IIThoratec

Baumwol,7 2010 40 Multipledevices

Inotropes >14 days, iNO > 48 h,Sildenal post iNO, RVAD

Severe TR

Kormos,4 2010 484 HM II Inotropes/vasodilators >14 days,RVAD

CVP/PCWP > 0.64, BUN > 39 ng/dL, MechVentilation

Patient characteristics Laboratory Haemodynamics

M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229 223Preoperative presence of severe TR and RV short/long axis ratio >0.6 have a high specicity (87%and 97%, respectively) and good sensitivity (66% and 37%) in identifying patients at risk of post-LVADRVF. Increasing severity of TR also directly correlates with the odds of occurrence of post-LVAD RVF.7 Ina small study by Puwanant et al.11 preoperative TAPSE 14 days, iNO for >48 h or RVAD implant. The sum of all points assigned toeach variable generated a prediction model, which stratied patients into four different risk groups.The incidence of RVF was 11% in the lowest risk group versus 83% for the highest group. Destinationtherapy was identied as a strong independent predictor in addition to increased PVR and the use ofa preoperative IABP.

Matthews et al.5 retrospectively looked at 197 LVAD recipients, 35% were complicated by RVF.Independent preoperative risk factors for RVF were identied (vasopressor use, AST, bilirubin and Cr)and a risk score developed (Table 5).

Female gender [ AST, ALT, bilirubin [2.0 mg/dL] CI < 2.2 l/min/m2Small BSA Y albumin RVSWI < 250Non-ischemic [ Cr [1.9 mg/dL], BUN CVP/PCWP > 0.64Previous heart surgery [ C-reactive protein, NT-proBNP Intraop [ CVPPreoperative inotropes Severe TR Intraop Y PAP/MAPMechanical ventilation Tricuspid annular motion < 7.5 mmMechanical circulatory assist RV SAX/LAX > 0.6

RV dysfunction: [ RVEDV, RVESV

BSA, Body surface area; BUN, blood urea nitrogen; CI, cardiac index; Cr, creatinine; CVP, central venous pressure; HM, HeartMate; IABP, intra-aortic balloon pump; iNO, inhaled nitric oxide; MAP, mean arterial pressure; PAP, pulmonary arterial pressure;PCWP, pulmonary capillary wedge pressure; RVAD, right ventricular assist device; RVEDV, right ventricular end diastolicvolume; RVESV, right ventricular end systolic volume; RV SAX/LAX, right ventricle short to long axis ratio; RVSWI, rightventricular stroke work index; TR, tricuspid regurgitation.

AST 80 IU/L 2 Cr 1.9 mg/dl 1.7 1Previous cardiac surgery 1.82.7 2A similar risk score was developed by Fitzpatrick31 in a slightly larger population of 266 patientsalso receiving different types of LVADs. In this retrospective study, RVF was dened as the need forRVAD, which was used in 34% of cases. An RVAD risk score was developed using the preoperative risk

SBP 96 mmHg 2.84.2 3>4.3 4Inotrope dependency 2.5Obesity 2ACE or ARB 2.5B-Blocker 2

Risk score Risk score Risk score

Total points Odds ratio Each variable valued: Total points Risk RVF [%]

3.0 0.49 1 [abnormal] or 0 [normal] use 12.5 83

Score < 50 predicts need for BiVAD

ACE, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; B-Blocker, beta blocker; Cr, Creatinine; CI,Cardiac Index; IABP, Intra-aortic balloon pump; RVSWI, right ventricular stroke work index; SBP, systolic blood pressure.Table 5Risk scores for RVF post-LVAD.

Matthews5 [2008] Fitzpatrick31 [2009] Drakos14 [2010]

Preoperative variables Points Preoperative variables Preoperative variables Points

Vasopressor use 4 Cardiac index 2.2 L/min/m2 Destination therapy 3.5Cr 2.3 mg/dl 3 RVSWI 0.25 mmHg L/m2 IABP 4Bilirubin 2 mg/dl 2.5 Severe RV dysfunction PVR

M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229224factors correlated to postoperative need for RVAD after LVAD implantation following multivariatelogistic regression analysis (Table 5). Using a formula, a score >50 was predictive of need for BiVADwith good sensitivity (83%) and specicity (80%).

The National Institutes of Health-sponsored Interagency Registry for Mechanical Assisted Circula-tory Support (INTERMACS) provided systematic data collection in the largest LVAD database in the US.A recent study comparing INTERMACS level I and II (sicker decompensating) to level III and IV patientsdid predict a higher risk of postoperative complications and mortality but did not sensitively predictpostoperative RVF or need for RVAD.32

Prevention and treatment of RV dysfunction

Meticulous attention to optimising preload, afterload and contractility in the perioperative period iscrucial to prevent RVF in patients with pre-existing RVD (Fig. 3). This includes simple measures such asmaintenance of normal sinus rhythm or AV synchronicity, adequate ventilation, temperature, acidbase balance and prevention of coagulopathy. There have been no studies to date that assess the impactof preoperative management on RVF post-LVAD.

Preoperative prevention

VanMeter et al.33 proposed a management algorithm that includes preoperative RV optimisation tomaintain a CVP

HR

80-100bpm

DDD Pacing Epinephrine Isoproterenol

Cardioversion MgSODigoxin

Rhythm

Normal Sinus

Mg SOLidocaine Amiodarone

Preload

CVP 10-15 mmHg

Contractility

CI > 2.0-4.0

Volume bolus

PDI Epinephrine Dobutamine

iNO

Diuresis Dialysis Decrease

LVAD flow

slow fast

abnormal

low

low

high

Interventricular

septum position

Decrease LVAD flow

Leftward bulge

TEE/TTE

M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229 225ineffective, continuous veno-venous haemodialysis (CVVHD) are effectivemeasures CVP and relieve RVdistension.15

Preoperative treatment of an elevated PVR is suggested33 but unsupported by any studies to date.The use of pulmonary artery catheters may be useful, as it allows continuous assessment of PAP andcareful titration of pulmonary vasodilators.

Preoperative coagulopathy predisposes to increased intra-operative bleeding. Intra-operative bloodtransfusions in this setting are particularly detrimental since these risk RV volumeoverload, increase PVRand worsen SIRS. Preoperative administration of vitamin K15,34 and intra-operative use of aprotinin35,36

are common practices to reduce bleeding that are validated by studies on rst-generation LVADs.Pharmacological support of LV function is key to maintaining adequate end-organ perfusion,

minimising hypotension and avoiding the vicious cycle of ischaemia further exacerbating heart failure.This may require the use of an IABP or temporary mechanical support devices37 when pharmacologicaltherapy is unsuccessful. Preoperative use of IABP is a risk factor for postoperative RVF6; nevertheless,some authors have a low trigger to use an IABP38 to ultimately preserve RV function.

Pharmacological management

LV dysfunction therapy such as beta blockade or angiotensin-converting enzyme inhibitors is notnecessarily ideal for RV dysfunction. Instead, consider supporting the RV with inotropes that allowsome pulmonary vasodilatation (dobutamine or milrinone) while maintaining adequate systolic bloodpressure (epinephrine) for coronary perfusion. Alpha-adrenergic stimulation of the RV may have an

CI, cardiac index; CVP, central venous pressure; HR, heart rate; iNO, nitric oxide; LVAD, left ventricular assist device; MAP, mean arterial pressure; Mg SO , magnesium sulphate; PDI, phosphodiesterase inhibitor; RVAD, right ventricular assist device; TEE, transesoephageal echocardiography

RV Afterload

PVR 40-100

dynes.s.cm

Phenylephrine Norepinephrine Vasopressin Methylene Blue

FlolanLungprotectiveventilation

high

MAP < 50mmHg Low LVAD flow Peripheral hypoperfusion

LV Afterload

SVR 800-1200

dynes.s.cm

low

Consider RVAD

Fig. 3. Management algorithm for RVF.

Intra-operative RVF may preclude weaning from CPB and necessitate alternative forms ofmechanical support. Given the lack of long-term RVADs, they are used as a rescue treatment whenconventional RVF therapy fails. No publication denes the criteria for RVAD implantation. In the largestseries reported to date, RVAD use occurred in 8% of patients post-LVAD implantation and correlatedwith poor outcome.9

In a small retrospective analysis by Fitzpatrick et al. elective BiVAD implantation correlated witha better 1 year, long-term and transplantation survival compared to emergent RVAD implant for acuteRVF post-VAD.8 Patients with severe RVF requiring BiVAD support were more severely ill, withsignicantly higher preoperative Cr and total bilirubin levels, IABP support, lower RVSWI, higher CVPTR is considered a run off mechanism for the failing RV and thus has not been aggressively treatedeven in patients at risk of RVF. Functional TR may worsen post-LVAD from a leftward septal shift witha consequent tethering of the TV septal leaet. Thus, the amount of residual TR should be carefullyassessed post-CPB by varying the LVAD pump ow. Correction of TR may indirectly contribute toimproved RV function by decreasing venous congestion and improving renal perfusion.

Different criteria have been proposed to proceed with TV repair during LVAD implant: TV annulus>40 mm,41 moderate42,43 or severe TR.44 In these small single-centre studies TV repair or replacementhas had a neutral impact reducing neither RVF nor morbidity and mortality post-LVAD.

Surgical consideration should be given to myocardial revascularisation45 to salvage hibernating RVmyocardium.

Modications to CPB technique consisting of an RA to LA bypass46 and PA to aorta bypass47 may benecessary to minimise RV overload and LVAD inow. Off-pump LVAD implant is becoming progres-sively popular as it has the obvious advantage of reducing blood loss and CPB-induced SIRS.48 Alter-native minimally invasive surgical approaches49 have been proposed to further minimise surgicalstress and postoperative morbidity.

Weaning from CPB may unmask acute RVF. Shortening CPB time, continuing ventilation during CPBand minimising transfusion-related lung injury are strategies that may avoid undesirable increases inPVR. Careful deairing of the heart under trans-oesophageal echocardiogram (TEE) guidance, before CPBweaning, is crucial to avoid systemic and right coronary air embolism. Alternatively, in-eld CO2insufation has been used to reduce air emboli.50 Successful CPB weaning involves gradually reducingCPB ows with an increase of LVAD ows as TEE monitors RV function, LV volume and IVS septal shift(Fig. 1). Maintaining the IVSmidline requires an adequate LV volume. If the LV is underlled it would behazardous to increase the pump speed to improve CO as this shifts the IVS leftward further impairingRV function (suction cascade).

After separation from CPB, low PVR should be maintained by choosing a protective mechanicalventilation strategy with low PEEP, avoiding hypoxia, hypercarbia and acidosis. Protamine adminis-tration, as a trigger for an acute PVR increase, should be deferred until stable haemodynamic has beenestablished.

Mechanical supportoverall negative inotropic effect. Differential contraction of the RV outow tract (RVOT)may predisposeto low RV CO from RVOT obstruction, particularly if the RV is underlled.

Specic pulmonary vasodilators (iNO and Flolan) may be required to reduce PVR and manage RVF.In a methodologically awed prospective study by Potapov et al., perioperative administration of iNOdid not signicantly reduce RV dysfunction.39 The authors admitted that it might be difcult to performa prospective study using this drug.

Mortality directly correlates with the duration of inotrope support and remains high even after theinotropes are stopped. Patients who tolerated earlyweaning of drugs (postoperative day 1) had a better6-month survival than those who did not.40

Surgical management

M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229226and CVP/PCWP ratio.

teristics, biomarkers, haemodynamic and echocardiographic parameters of RV dysfunction. Severalrisk scores to predict the risk of RVF have been developed but none has been prospectively validated.

Prevention of RVF relies on treatment of modiable preoperative risk factors and optimisation of RVfunction. This consists of decreasing RV preload and afterload while maintaining adequate end-organperfusion. Intra-operative management minimises blood transfusion and CPB time to avoid worseningPVR. Surgical correction of TR may also improve postoperative morbidity.

There are no specic guidelines for treating RVF post-LVAD implant. RVAD insertion is a lastrecourse when RVF is refractory tomedical treatment. There is some evidence that earlier institution ofRVAD or elective BiVAD is benecial.

Practice points

The RV is anatomically and functionally distinct from the LV and more sensitive to changes inafterload (PVR).Management of RVF in the LVAD patient relies on maintaining sinus rhythm and contractility,optimising preload and reducing PVR.Correction of preoperative coagulopathy, use of off-pump technique and attention to surgicalhaemostasis may minimise the need for transfusions and benet postoperative RV function.Adequate RV protection, careful deairing and slow progressive increase of LVAD ow are key forsuccessful weaning from CPB.For newer-generation continuous-ow LVADs maintaining the interventricular septum ina neutral position is crucial to optimising RV function.

Research agenda

M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229 227Conict of interest

None declared.

References

1. Miller LW, Pagani FD, Russell SD et al. Use of a continuous-ow device in patients awaiting heart transplantation. N Engl JMed 2007 Aug 30; 357(9): 885896.

*2. Slaughter MS, Rogers JG, Milano CA et al. Advanced heart failure treated with continuous-ow left ventricular assist

Further research is needed to prospectively study the impact of risk scores in identifying heartfailure patients at risk for RVF.Development and validation of standardised algorithms to manage RVF may improve outcomein these patients.Dening guidelines for BiVAD implantationwould benet patients likely to experience RVF post-LVAD implantation and provide the institution of more timely mechanical support.Early RVAD implantation at the time of LVAD surgery improved survival to transplant (70% vs. 52%)compared to RVAD insertion>24 h post-LVAD surgery.51 The use of an RVAD however reduced survivalafter transplantation at 1, 5 and 10 years compared to those not requiring RVADs. RVAD implantation isan independent predictor of mortality in LVAD patients as a BTT.4

To summarise, RVF post-LVAD implant is a frequent serious problem, which worsens morbidity,mortality and hospital length of stay. LVAD support with the new continuous-ow devices modies RVgeometry by septal displacement and increasing RV preload. These changes may lead to RVF ina patient with pre-existing RVD. RVF post-LVAD is multifactorial; risk factors include patient charac-device. N Engl J Med 2009 Dec 3; 361(23): 22412251.

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*4. Kormos RL, Teuteberg JJ, Pagani FD et al. Right ventricular failure in patients with the HeartMate II continuous-ow leftventricular assist device: incidence, risk factors, and effect on outcomes. J Thorac Cardiovasc Surg 2010 May; 139(5): 13161324.

*5. Matthews JC, Koelling TM, Pagani FD et al. The right ventricular failure risk score a pre-operative tool for assessing the riskof right ventricular failure in left ventricular assist device candidates. J Am Coll Cardiol 2008 Jun 3; 51(22): 21632172.

*6. Patel ND, Weiss ES, Schaffer J et al. Right heart dysfunction after left ventricular assist device implantation: a comparison ofthe pulsatile HeartMate I and axial-ow HeartMate II devices. Ann Thorac Surg 2008 Sep; 86(3): 832840. discussion -40.

7. Baumwol J, Macdonald PS, Keogh AM et al. Right heart failure and "failure to thrive" after left ventricular assist device:clinical predictors and outcomes. J Heart Lung Transplant 2011 Aug; 30(8): 888895.

*8. Fitzpatrick 3rd JR, Frederick JR, Hiesinger W et al. Early planned institution of biventricular mechanical circulatory supportresults in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assistdevice. J Thorac Cardiovasc Surg 2009 Apr; 137(4): 971977.

9. Kirklin JK, Naftel DC, Kormos RL et al. Third INTERMACS annual report: the evolution of destination therapy in the UnitedStates. J Heart Lung Transplant 2011 Feb; 30(2): 115123.

*10. Hennig F, Stepanenko AV, Lehmkuhl HB et al. Neurohumoral and inammatory markers for prediction of right ventricularfailure after implantation of a left ventricular assist device. Gen Thorac Cardiovasc Surg 2009 Jan; 59(1): 1924.

11. Potapov EV, Stepanenko A, Dandel M et al. Tricuspid incompetence and geometry of the right ventricle as predictors ofright ventricular function after implantation of a left ventricular assist device. J Heart Lung Transplant 2008 Dec; 27(12):12751281.

12. Dang NC, Topkara VK, Mercando M et al. Right heart failure after left ventricular assist device implantation in patients withchronic congestive heart failure. J Heart Lung Transplant 2006 Jan; 25(1): 16.

13. Santambrogio L, Bianchi T, Fuardo M et al. Right ventricular failure after left ventricular assist device insertion: preop-erative risk factors. Interact Cardiovasc Thorac Surg 2006 Aug; 5(4): 379382.

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15. John R, Lee S, Eckman P et al. Right ventricular failurea continuing problem in patients with left ventricular assist devicesupport. J Cardiovasc Transl Res 2010 Dec; 3(6): 604611.

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49. Ghodsizad A, Kar BJ, Layolka P et al. Less invasive off-pump implantation of axial ow pumps in chronic ischemic heartfailure: survival effects. J Heart Lung Transplant 2011 Jul; 30(7): 834837.

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M. Meineri et al. / Best Practice & Research Clinical Anaesthesiology 26 (2012) 217229 229

Right ventricular failure after LVAD implantation: Prevention and treatmentIntroductionPhysiology and pathophysiology of RV functionNormalHeart failurePost-LVAD implantation

Assessment of RV functionStructure and functionPost-LVAD implantation

Definition and predictors of RV failureDefinition RVFRisk factorsRisk scores

Prevention and treatment of RV dysfunctionPreoperative preventionPharmacological managementSurgical managementMechanical support

Conflict of interestReferences