weaning from mechanical circulatory support after long controversy about the clinical relevance of unloading - promoted recovery from chronic heart failure ( hf ) and about the feasibility of elective weaning of patients from their ventricular assist device ( vad ) , taking into account the risk of early post - weaning hf recurrence , this topic has gained increasing interest over the past 10 years , especially after the publication of the first long - term weaning results in patients with chronic hf reversal after lvad implantation .
assessment of cardiac recovery temporary interruptions of mechanical unloading (  off - pump trials  ) are mandatory for assessment of recovery , regardless of whether the assessment is performed at rest or during exercise .
short off - pump trials allow evaluation of the heart without mechanical support under the same circumstances that will exist after vad removal .
however , whereas pulsatile vads allow optimal assessment of heart function during complete pump stops , complete stops of axial - flow pumps lead to retrograde flow into the lv followed by reduction of the diastolic arterial pressure that , by reducing the left ventricular ( lv ) afterload , can generate overestimations of lv systolic function . according to our observations , the misleading retrograde bloodflow into the lv during off - pump trials is a major negative factor that can interfere with successful vad explantation .
therefore , for such pumps , rotor - speed reduction to values resulting in close to zero flow in one cardiac cycle ( 3000 - 6000 rpm ) is better than complete pump - stop .
before off - pump trials , heparin must be given ( 60 - 100 iu / kg according to the prothrombin time reported as inr ) to prevent thrombus formation inside the pump .
patients with heparin - induced thrombocytopenia should receive argatroban ( synthetic thrombin inhibitor ) infusions ( 2g / kg / min)which should be started 1h before the off - pump trials .
additionally , completely stopped pulsatile devices should be allowed to pump at least once a minute , or 3 bursts of pneumatic hand - pumping should be intercalated every 15 to 60 seconds to prevent blood stagnation [ 2 , 4 , 5 , 7 , 8 ] . in patients with a biventricular assist device ( bivad ) it appeared appropriate to stop the right ventricular ( rv ) pump 30 seconds earlier than the lv pump ; after both pumps are deactivated , evaluation of recovery can be performed .
duration of individual off - pump periodscan vary between 3 and 15 minutes . in patients with insufficient recovery for possible vad removal ,
as already shown during the first 3 minutes , there is no reason to further extend the off - pump trial . with appropriate caution
, the risk of interruption of unloading is low  [ 4 , 6 , 9 , 10 ] . in weaning candidates
it appears useful to conduct such trials weekly or every 2 weeks and to make the final decision for elective vad explantation only after cardiac improvement has reached its maximum ( no further improvement in at least 2 consecutive off - pump trials ) . during recovery
it appears useful to change the working mode of the pumps , in order to intensify the unloading if the ventricle size needs further reduction , or to exert moderate load on the ventricular myocardium after maximum improvement [ 1 , 5 , 7 ] .
in addition to the retrograde blood flow into the lv during off - pump trials , which makes the evaluation of lv function very difficult , another factor that may impair successful vad explantation in the subgroup of patients receiving continuous vad is the usually great difficulty in maintaining the recovered heart in a state as unmolested as possible throughout explantation surgery . during vad removal , which was performed on the beating heart in all our weaned patients ,
we aimed to leave the intrathoracic part of both cannulas in place after they were reliably occluded [ 6 , 9 ] .
this was possible in 91% of patients with pulsatile pumps , but only in 57% of patients with continuous - flow pumps .
also , the heart - lung machine , which was used only in less than 10% of patients with pulsatile vads , was required for all continuous - flow - pump explantations .
nevertheless , in our patients with non - ischemic chronic cardiomyopathy , there were no significant differences in the 3-year post - explant freedom from hf recurrence between patients weaned from pulsatile and those weaned from continuous flow pumps .  
cardiopulmonary exercise testing is also increasingly used by some centers [ 4 , 8 ] .
echocardiography is the cornerstone for assessment of cardiac recovery allowing both selection of potential weaning candidates and decision - making in favor of or against vad removal .
after vad implantation , repeated transthoracic echocardiography ( tte ) screenings with normal vad function are necessary for selection of potential weaning candidates , i.e. patients with signs of relevant reverse remodeling who also seem to have their contractile function improved to levels deserving further evaluation .
such potential weaning candidates are those with lv end - diastolic diameter ( lvedd ) < 55 mm ( or 55 - 60 mm at bsa 1.8m)and fractional shortening ( fs)>15% , no or  grade i mitral and/or aortic regurgitation , no rv dilation and tricuspid regurgitation  grade ii . before the first off - pump trial
, it is useful to perform stepwise pump - rate reductions under tte monitoring , to verify whether complete interruption of unloading is possible . thus , if incomplete unloading interruption alreadyprovokes symptoms ( dizziness , sweating , etc . ) , complete interruption of unloading is senseless and risky . if the patient remains asymptomatic but the lvedd increases beyond 60 mm , a complete interruption is also senseless , because such a patient is not yet a weaning candidate .
echocardiographic assessment of recovery in weaning candidates is usually based on the results of repeated off - pump trials at rest [ 2 , 4 , 7 , 9 ] .
after months of intensive vad support , even short periods of physiological loading by interruption of unloading may represent a serious challenge for a possibly incompletely - recovered ventricle .
it therefore appears reasonable to avoid ( at least initially ) any risk of myocardial exhaustion , which might interfere with possibly still ongoing recovery . for this reason ,
all 119 patients who were weaned since 1995 in our center from long - term vads primarily designed as a bridge - to - htx or as permanent therapy underwent assessment of heart function exclusively at rest [ 6 , 9 , 10 ] .
although at rest the conclusive value of assessments is limited by the lack of information about inotropic reserves and cardiac adaptation to stress , our weaning results appeared not to be relevantly affected by that , insofar as the results reported by groups who also used stress echocardiography and/or exercise testing were not better [ 4 , 9 , 11 ] .
however , stress echocardiography can provide valuable information on inotropic reserves and adaptation to stress , which might be useful for weaning decisions . according to certain authors ,
an absolute ef increase by 5% during dopamine infusion indicates preservation of contractile reserve . a possible limitation of dobutamine stress echocardiographycan be , at least theoretically , the risk of myocardial exhaustion with negative impact on an ongoingmyocardialrecovery process .
further studies are therefore necessary to establish the real value of dobutamine stress echocardiographyfor weaning decisions . in principle
, off - pump tte should be as comprehensive as possible , including tissue doppler and strain imaging .
* rwted = [ interventricular septum thickness + posterior wall thickness ] / lvedd . * * product of time velocity integral measured with pulsed - wave doppler at the lv outflow tract ( lvot ) and cross - sectional area of the lvot .
however , not all these parameters can be reliably measured in all patients because of poor image quality in some patients with vad support .
image quality was a serious limitation , especially for off - pump doppler measurements that had to be performed during rotor - speed reduction instead of complete pump stop .
off - pump right heart catheterization off - pump right heart catheterization ( rhc ) is also a cornerstone for recovery assessment [ 4 , 9 ] and is necessary for final decisions in favor of or against vad explantation . a final off - pump trial of 15minutes in the operation room , with repeated measurements of hemodynamic parameters under continuous echocardiographic monitoring , is indispensablebefore the start of explantation surgery .
rhc appeared also necessary before any preliminary decision - making in potential weaning candidates with borderline tte data and/or relevant cardiac improvement only after > 6 months of unloading and/or long history duration ( > 3 years ) of hf . in patients with axial - flow pumps , such preliminary rhc appears more reliable if off - pump measurements are preceded by occlusion of the outlet cannula with a balloon .
normal and stable hemodynamics during off - pump rhc trials is a necessary condition for a decision in favor of vad removal , but not sufficiently predictive for long - term post - explant cardiac stability [ 6 , 9 ] .
it was observed that , unlike non - recovered patients , those with unloading - promoted recovery show a significant lvef increase in the 6-minute walking test ( 6mw ) .
non - recovered patients showed a significant correlation between heart rate ( hr ) and mean arterial pressure ( map ) after 6mw , suggesting that hr increase was compensatoryfor map reduction , whereas recovered patients showed after the 6mw no correlation between hr and map , suggesting that hr increase was independent of map change and therefore a true inotropic reserve response .
harefield hospital ( uk ) developed an algorithm for testing recovery that includes a 6mw test with repeated measurements afterwards to determine the inotropic reserve [ 4 , 8 ] . the same group also uses cardiopulmonary exercise testing with oxygen uptake ( vo2 ) as a parameter for weaning decisions .
decision - making in favor of vad explantation our weaning criteria that have evolved during nearly 20 years of weaning experience are summarized in table 2 . main left ventricular assist device ( lvad ) explantation criteria * *  thesecriteria used at present at the deutsches herzzentrum berlin have evolved from a weaning experience of 18 years after explantation of 100 long - term vads , primarily designed as bridge - to - htx or permanent therapy .  * * measurements at rest , without inotropic support .   since 2005 also
speckle - tracking derived 2d - strain imaging parameters ( global longitudinal strain and strain rate , intra - ventricular synchrony and synergy , including pre - explant stability of all these parameters after maximum improvement and during the final off - pump trial ) were taken into consideration for weaning decisions .  
essential criteria are , in addition to a stable off - pump lvef 45% , normal and stable lv size and shape , as well as high stability of hemodynamic parameters measured during the off - pump right heart catheterization ( rhc ) trials [ 6 , 9 ] . even in patients with good recovery
, it appears useful to explant vads only after the recovery has reached its maximum ( no further improvement during the next 2 - 4 weeks ) .
if a relevant lvef reduction and/or lv enlargement occurs during the next 2 - 4 weeks after maximum cardiac recovery , it can be risky to explant the vad , even if the lvefdid not fall below 45% and thelvedddid not increase beyond55 mm .
the weaning criteria used by the harefield group include fewer tte parameters ; instead they usethe 6mw - test and the peak oxygen consumption ( vo2)(optimal : >
however , it is important to emphasize that they also do not explantlvadsin patients with lvef < 45% [ 4 , 6 , 9 ] . for more reliable evaluation of cardiac recovery , since 2005 we have also used tissue doppler and  speckle - tracking - derived 2d - strain imaging [ 12 , 13 ] .
the potential usefulness of tissue doppler wall motion velocity measurements is shown in figure 1 .
usefulness of left ventricular ( lv ) peak systolic wall motion velocity ( sm ) measurements at the basal posterior wall by pulsed - wave tissue doppler toassess the stability of lv contractile function during and between off - pump trials and for detection of further cardiac improvement after  left ventricularejection fraction ( lvef ) has reached its peak value . at the time when lvef reached its maximum value ( 55% ) , sm was 9cm / s during full left ventricular assist device ( lvad ) support ( a ) and remained stable during the off - pump trial ( b ) . although the lvef remained unchanged , the sm values with ( c ) and without(d ) lvad support increased during the next 3 weeks of unloading up to 11cm / s ( + 22% ) .
the advantages of strain imaging are its ability to differentiate between active and passive movement of myocardial segments , the angle independency of deformation - velocity measurements , and the possibility to quantify intra - ventricular asynchrony and dyssynergy and to evaluate components of myocardial function , such as longitudinal myocardial shortening , thatcannot be visually assessed
.  unfortunately , as 2d - strain imaging is a new method ,  the available off - pump data  are insufficient for reliable assessment of  their predictive value for long - term post - explant  cardiac stability .  however , in borderline cases
, off - pump data on deformation velocity as well as on intraventricular synchrony and synergy of contraction , including their stabilityafter maximum improvement , can be useful for weaning decisions .
figures 2 and 3 show the potential usefulness of 2d - strain imaging for assessment of recovery after lvad implantation .
usefulness of speckle - tracking derived 2d - stain imaging for assessment of cardiac recovery after left ventricular assist device ( lvad ) implantation . the comparison of recordingsobtained before lvad implantation ( a and b ) and several months later before lvadexplantation ( c and d ) showed a striking improvement of systolic global longitudinal strain ( myocardial longitudinal shortening ) and strain - rate ( velocity of myocardial longitudinal shortening ) which increased during lvad support from 4% ( a ) and 0.3/s ( b ) , respectively to 17.5% ( c ) and 9.6/s ( d ) , respectively .
the global early diastolic strain rate ( early relaxation velocity ) also increased from 0.7/s ( b ) to 1.6/s ( d ) and image d also shows a normalization of early / late strain - rate ratio .
speckle - tracking derived 2d - strain and strain rate off - pump recordings showing further cardiac improvement during left ventricular assist device ( lvad ) support after off - pumpleft ventricularejection fraction(lvef ) reached its maximum value of 50%.at the time of maximum lvef improvement ( images a and b ) longitudinal global systolic strain ( sl ) and strain - rate ( srl ) were slightly reduced ( 17% and 1/s , respectively ) and the global early / late diastolic strain - rate ratio(srle / srla ) was high .
after few weeks of further lvad support , although the lvef remained unchanged , both slandsrl increased , reaching normal values ( 22% and 1.25/s , respectively ) and there was also improvement in intraventricular synchrony of contraction ( images c and d ) .
the 35% shortening of the time to peak strain rate ( tpsr ) additionally indicates improvement of left ventricular ( lv ) systolic function . the early relaxation velocity increase ( from 1.7/s to 2.1/s ) and the srle / srla ratio reduction ( from 3.5 to 2.1 )
off - pump lvef  45% plus normal lvedd at rest are basic weaning requirements and their stability after maximum improvement over the next 2 to 4 weeks during and between additional off - pump tests is predictable for long - term post - explant patient outcome .
tissue doppler andstrain imaging data are useful for decision making especially if their stability after maximumremission is also considered .
after maximum improvement , stable size , geometry and function also during moderate loading of theventricle by pump speed reduction for several days can be helpful for weaning decisions .
stable normal off - pump hemodynamics is necessary for weaning decision , but insufficiently predictive for long - term cardiac stability aftervad removal .
cardio - pulmonary exercise testing ( with vad support and during off - pump trials ) provides information on inotropic reserve and can be useful for weaning decisions .
 for selected patients ventricular assist device explantation is feasible . 
 freedom from heart transplantation and vad support for > 15 years following vad removal is possible even if recovery is incomplete and the underlying cause for ventricular assist device implantation was a chronic form of cardiomyopathy . 
 echocardiography and rightheart catheterization are necessary to assess cardiac recovery . however 
 , to date there is no gold standard for recovery assessment . 
 certain echocardiography parameters appeared highly predictive for long - term ( 5 years ) post - weaning cardiac function and reliable for weaning decisions . 