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ISHLT consensus statement for the selection and management of pediatric and congenital heart disease patients on ventricular assist devices Endorsed by the American Heart Association
Heart failure (HF) is a significant cause of mortality in children and therefore there is interest in understanding the optimal way to support these children with Ventricular Assist Devices (VAD) to improve outcomes. VAD therapy is now regarded as an important treatment option in pediatric HF. The 2019 International Society for Heart and Lung Transplantation (ISHLT) registry report shows that there is an increasing trend towards using VADs as a bridge to transplant (BTT) with currently over one-third of patients transplanted being bridged with a VAD.
The immediate aim of VAD therapy is to provide hemodynamic stability for a failing circulation unresponsive to medical therapy. The VAD should be implanted before the development of severe end-organ dysfunction in order to optimize clinical outcomes. The goal is to improve tissue and organ perfusion, improve quality of life (QoL) and improve waitlist survival. Importantly, VAD therapy may not only lead to patient stability but may also afford the opportunity for patient rehabilitation prior to heart transplantation (HT).
Despite the increase in VAD use within pediatrics over the last decade, the majority of centers implant less than 10 VADs in children per year.
Outcomes of children implanted with ventricular assist devices in the United States: first analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Thus, local data is limited for analysis of outcomes and therefore multi-center collaboration and consensus is essential in understanding this complex and dynamic field.
ISHLT has recognized the importance of a consensus statement on the selection and management of pediatric and congenital heart disease (CHD) patients undergoing VAD implantation. The purpose of this document is to provide expert-consensus derived recommendations and whenever possible, these recommendations shall be guided by evidence. The creation of this consensus document required multiples steps including the engagement of the ISHLT councils, identification and selection of experts in the field, and the development of 13 Tasks Forces. Extensive literature searches were performed but due to the lack of comparative trials in pediatrics, this document was written as a literature review with expert opinion rather than based on level of evidence.
Patient selection
Timing of VAD
Optimal timing for the implantation of a VAD in pediatric patients should be determined by an assessment of the potential risks and benefits of the intervention. The complexity of this decision-making is amplified by the numerous variables impacting VAD risk profile, including patient age/size,
Outcomes of children with congenital heart disease implanted with ventricular assist devices: an analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs).
Outcomes of pediatric patients supported with continuous-flow ventricular assist devices: a report from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Many of these factors are interdependent. Paracorporeal devices are most often placed in younger, smaller patients who are more likely to be sicker, have CHD, and end-organ dysfunction at the time of VAD implantation, making it difficult to assess which of these factors drives inferior outcomes.
While this complex reality precludes the formulation of any generalizable guidelines for the optimal timing of VAD placement for all pediatric patients, one consistent theme to emerge from the literature is the inferior outcomes of VAD support for pediatric patients in cardiogenic shock (INTERMACS Profile 1) or with end-organ dysfunction prior to implant.
(Figure 1) Despite these data, the most recent Pedimacs report reveals that 33% of patients are still INTERMACS Profile 1 at the time of implant, including 40% of patients receiving paracorporeal pulsatile devices, 49% of patients receiving paracorporeal continuous flow devices, and 19 % of patients receiving intracorporeal continuous flow devices .
Although, patients have better outcomes if implanted before they become too ill, there are times when pediatric patient present in cardiogenic shock and/or with end-organ injury. In these cases, attempting to reverse the shock process before implantation of a durable VAD may possibly result in better outcomes. The role of paracorporeal continuous flow (CF) and percutaneous VADs, or venoarterial extracorporeal membrane oxygenation (ECMO) in stabilizing/salvaging critically ill pediatric patients with advanced HF to make them better candidates for long term support is not well understood to date. There is evidence that end-organ dysfunction in children can improve significantly with a paracorporeal CF device and this may have a beneficial effect on outcomes.
although it is difficult to separate the impact of ECMO from the level of illness requiring ECMO in interpreting this data.
Indications for VAD
Failure of medical management: In many cases, medical management does allow stabilization of patients with HF. In some cases, HF progresses and VAD therapy is the only option for stabilization. Progressive respiratory (requiring non-invasive and invasive support) decompensation, liver dysfunction, kidney injury and feeding intolerance are commonly reported measures of congestion and/or inadequate cardiac output (CO) that may develop despite optimal medical management. End-organ dysfunction is common in pediatric VAD patients prior to implantation, with 45% of patients intubated (paracorporeal devices 75-85% of patients compared to intracorporeal devices 21%), 94% on inotropes, 64% requiring feeding tubes/TPN, 40% with hyperbilirubinemia and 30% having a glomerular filtration rate (GFR) < 60 mL • min−1 •1.73 m.
Outcomes of children implanted with ventricular assist devices in the United States: first analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Post-cardiotomy failure to wean from cardiopulmonary bypass (CPB): The presence of a previous sternotomy or additional cardiac surgery in pediatric VAD patients ranges from 23% to 39%.
Post-cardiotomy patients (in most circumstances those with CHD), who fail to wean from cardiopulmonary bypass (CPB) are more likely to be converted to ECMO or implanted with paracorporeal CF devices. With respect to the use of more durable VADs, failure to wean from CPB or decompensation during the index hospitalization after cardiac surgery is a significant risk factor for mortality among patients supported with a EXCOR.
Uncontrollable Arrhythmias: Cardiogenic shock from uncontrolled tachyarrhythmia is rare and most of the literature pertaining to mechanical circulatory support (MCS) involves case reports and the use of ECMO. VAD support was deemed necessary in 10% (n = 39) of patients in the only multicenter retrospective review
The primary indication for pediatric VAD use in North America remains BTT, with 55% of patients listed at time of implantation and 34% being assessed for candidacy.
Similar frequency of intent has also been recently reported in the second Paedi-EUROMACS report with 85% of patients implanted with an intention to transplant with 56% BTT and possible BTT 29%.
Although most patients are implanted with the intent to transplant, pediatric DT is becoming more common especially in patients with muscular dystrophy (MD) and congenital heart disease (CHD) patients.
End-Organ Assessment: Although pre-operative renal, hepatic, respiratory and nutritional failure have been associated with worse post-VAD outcomes, many patients have pre-operative end-organ dysfunction.
This likely is due to late presentation, late diagnosis or delayed timing for implantation. Irreversible renal dysfunction has been considered a relative contraindication to VAD implantation in the past but identifying irreversible dysfunction remains a significant challenge. Current data is complicated by various definitions of renal dysfunction including: serum creatinine > 1.6 mg/dl for patients aged > 10 years, or creatinine > 1.0 mg/dl for patients aged ≤ 10 years, or by the estimated glomerular filtration rate (eGFR) using the Schwartz formula
Outcomes of children implanted with ventricular assist devices in the United States: first analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
In the 3rd Pedimacs report, the threshold was defined as <60 mL/min1/1.73 m2 and found that 30% of patients had renal insufficiency with 5% found to have an eGFR <30 mL/min1/1.73 m2 or requiring dialysis.
Congestive hepatopathy resultant from HF has also been associated with both morbidity and mortality post-VAD. Elevated ALT/AST values are reported in up to 22% to 25% of patients, and abnormal bilirubin in 40% to 45% of patients at the time of VAD.
Mortality has been shown to be higher in patients with elevated bilirubin levels, and is particularly high for patients with additional risk factors, such as patients, weighing less than 10kg (mortality 70%).
The use of mechanical ventilatory support is reported in up to 45% to 49% of patients with 23% to 27% requiring ongoing medical paralysis at the time of VAD implantation.
However, significant differences are seen between the device type implanted, with only 21% of intracorporeal CF-VAD patients intubated at the time at implantation.
Poor pre-operative nutrition secondary to poor appetite, abdominal discomfort and nausea may represent symptoms of inadequate gut perfusion from low CO states or venous congestion. The presence of tube feeding, TPN or a combination of both has been reported in up to 64% of patients undergoing VAD implantation.
Right Heart Assessment: “Right heart failure” (RHF) in children after LVAD implant is difficult to quantify, but has been shown to have an incidence as high as 42%.
Although right ventricular dysfunction is common, this can typically be managed medically as BiVAD is relatively uncommon in the pediatric VAD population (15% of patients in the most recent Pedimacs cohort).
Many clinical and imaging parameters have been used to assess the right ventricular (RV) function prior to VAD, however none of the individual parameters have been a sole predictor of the need for RV support. Echocardiography may be used to qualitatively assess RV systolic function, and semi quantitative measures such as tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change can be used for RV functional assessment; however, the value of any individual echocardiographic parameter in predicting RV failure and/or the need for BiVAD support is limited.
Estimation of RV pressure through measurement of tricuspid regurgitation jet velocity and position of the inter ventricular septum can also be used to screen for elevated pulmonary arterial pressures as an indicator of elevated pulmonary vascular resistance (PVR). Cardiac catheterization to measure CO, central venous pressure (CVP), and pulmonary capillary wedge pressure often occurs prior to VAD placement, but this is neither practical nor safe in all patients. Finally, assessment of cardiac rhythm is imperative. Sustained ventricular arrhythmias not controlled by pharmacologic measures may contribute to RHF and need for BiVAD support in the perioperative period.
Numerous clinical, imaging, and hemodynamic parameters have been identified in the adult VAD literature as tools for predicting the need for BiVAD support; these include preoperative mechanical ventilation, preoperative renal replacement therapy, elevated CVP, and severe RV systolic dysfunction.
Despite these parameters, the decision to proceed with BiVAD support is typically made intraoperatively. If RVAD support is needed, temporary RV support may be considered to allow RV recovery following CPB and decompression of the RV and improvement of fluid overload.
Support Type Assessment: After establishing that a patient requires a VAD, an important subsequent step is determining the kind of support needed. This refers to the support of the systemic or LV alone (SVAD or LVAD) versus biventricular support (BiVAD). While support of the RV alone (RVAD) may also be considered, it is uncommon. Consideration of LVAD versus BiVAD support is relevant only to patients with biventricular circulations. For patients with single ventricle circulation, however, it is critical to recognize that adequate support of the circulation with a systemic VAD (SVAD) may result in suboptimal outcomes if the patient's circulatory derangement results wholly or in part from perturbations in the Fontan pathway.
Carlo WF, Villa CR, Lal AK, Morales DL. Ventricular assist device use in single ventricle congenital heart disease, Pediatr Transplant 21(7), Published online September 15, 2017. doi:10.1111/petr.13031.
Psychosocial Assessment: A thorough patient and family psychosocial assessment is critically important pre-VAD implant. The goal of the psychosocial assessment is to identify patient and family strengths, weaknesses and intervention needs, particularly as they relate to VAD care demands. Similar to pediatric pre-heart transplant listing, primary domains of the pre-VAD psychosocial evaluation should minimally include: patient and family treatment adherence, barriers to medical management, disease and VAD-related knowledge, cognitive and/or neurodevelopmental functioning, current and historic mental health, substance use, social support, family functioning, and abuse and legal history.
Device “fit”: Innovative imaging techniques using virtual device implantation have become available and evolved as an accepted pre-operative planning tool.
Translation of First North American 50 and 70 cc total artificial heart virtual and clinical implantations: utility of 3D computed tomography to test fit devices.
This is especially relevant to children that are being considered for a device that has been U.S. Food and Drug Administration (FDA)-labeled for a larger-sized patient. Accurately scaled 3-dimensional (3D) surface rendering of the device are placed within a 3D reconstruction of the chest to assess for individual fit. Thus device compression of pertinent intrathoracic structures may be ruled out as well as assessing the ability of the inflow cannula to fit within the ventricular cavity.
It must be emphasized that these virtual assessments are typically performed on the preoperative geometry of the heart. Cardiac geometry, however, can be significantly different once decompressed with VAD, which has become more predictable as experience has increased.
Key Points
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In general, VAD implantation should be considered, prior to significant end-organ dysfunction or clinical deterioration.
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Patients in cardiogenic shock, or INTERMACS Profile 1, have increased mortality rates post VAD therefore stabilization prior to durable support should be considered.
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Pre-implant planning is a key step in determining eligibility for VAD therapy and should include assessment of end-organs, surgical planning and psychosocial assessment.
Device selection
Devices available for children with end-stage HF can be classified in a number of ways (Table 1). They can be dichotomized by anticipated duration of therapy (temporary or durable) or by design and function (PF or CF). Devices can further be separated by site of implantation (paracorporeal, extracorporeal, intracorporeal, or intravascular) as well as by what form of circulatory support they provide: LV, RV, SV, BiV or total heart replacement (TAH).
Pulsatile Flow Devices: The Berlin Heart EXCOR (Berlin, Germany) is a pneumatically driven paracorporeal VAD, which has been the mainstay of support throughout the world for children for over two decades. In the U.S., the EXCOR is the only device FDA-approved VAD for children. The EXCOR pump comes in a number of sizes (named after their stroke volume) allowing support of children and adults across a broad weight range (3 kg and greater). However, the device is being used most frequently in children <20 Kg.
Various implantation options are available and the pump can be used to as a LVAD, RVAD, SVAD or BiVAD configuration. The EXCOR can only be used for inpatients in the U.S., but other countries allow patient discharge on a mobile driver. The Syncardia (t-TAH, Tucson, Arizona, USA) is a pulsatile, durable device that is intracorporeal and pneumatically driven. The device provides biventricular support following cardiectomy. In the pediatric and CHD population, it has played a role in many scenarios including support of the patient with graft failure post-transplant (as immunosuppression can be withdrawn after TAH implantation) and support of complex CHD including the Fontan circulation.
Only two sizes of device are available, both FDA approved, one with 70 mL chambers and one with 50 mL chambers. The smaller device used in patients with a Body Surface Area (BSA) <1.5m.
Outcomes of children implanted with ventricular assist devices in the United States: first analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
The device was developed with intent to discharge patients post-implantation, and hence mobile drivers exist for use out of the hospital.
Continuous Flow Devices: Various paracorporeal, temporary pump heads are available that can be used to provide support of either or both ventricles in children. The most commonly used pumps are the RotaFlow (Maquet) centrifugal pump and the Centrimag/Pedimag (Abbott Laboratories) magnetically levitated devices. In either case, various cannulas can be used to surgically connect the pump head to the circulation allowing flexibility in application and the potential to initiate support without going on cardiopulmonary bypass. This flexibility makes these devices useful for both recovery and in challenging settings such as CHD. While these devices are by their nature temporary forms of support that require in hospital admission, they may be utilized as a long-term BTT or BTR.
Outcomes of children supported with devices labeled as "temporary" or short term: a report from the Pediatric Interagency Registry for Mechanical Circulatory Support.
Other products exist as short-term circulatory support devices primarily targeted at circulatory rescue in adults. The TandemHeart is an intravascular device connected to a centrifugal pump that can be placed intravenously to support the RV with ejection to the pulmonary artery (or the LV through a trans-septal approach) and has been used in pediatrics as an extracorporeal device for Left Ventricular (LV) support and Single Ventricular (SV) support.
The Impella (Abiomed) device, available in multiple sizes, is also an intravascular device with an axial pump designed to be placed across the aortic valve and into the LV to allow short term emergent ventricular support.
The Impella can also be used for RV support, although there is limited experience in pediatrics.
Various intracorporeal durable devices are available for adults and are also used (off-label in the U.S.) for larger children and adolescents in many countries. The current implantable continuous flow (CF) devices includes the axial flow, HeartMate II, (Abbott Laboratories, IL, US), centrifugal hydrodynamic flow HVAD System, (Medtronic, Minneapolis, MN, US) and centrifugal full-mag Lev HeartMate 3 (Abbott Laboratories). These devices are designed for long-term support and are implanted with the intention to discharge. The size of these devices limit their use in children and implantation is generally considered at >15 -20 kg (although smaller implantations have been described).
Early experience with the HeartMate 3 continuous-flow ventricular assist device in pediatric patients and patients with congenital heart disease: a multicenter registry analysis.
The HVAD device has been utilized more frequently in smaller children due to the size of the pump, although the new HM3 has gained attention in children due to its shorter inflow and favorable adverse event profile.
Early experience with the HeartMate 3 continuous-flow ventricular assist device in pediatric patients and patients with congenital heart disease: a multicenter registry analysis.
Association of clinical outcomes with left ventricular assist device use by bridge to transplant or destination therapy intent: the multicenter study of MagLev technology in patients undergoing mechanical circulatory support therapy with HeartMate 3 (MOMENTUM 3) randomized clinical trial.
Similar to the adult intracorporeal devices, a miniature CF axial pump, the Jarvik (Jarvik Heart Inc, New York City, New York, USA), is currently under study through an industry collaboration with the NIH (PumpKIN trial).
After the decision to place a VAD has been made, the next crucial step is to determine the level of support needed (LVAD vs SVAD or BiVAD in biventricular circulation).
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Important considerations for device selection include patient-device size matching; implant configuration LVAD, SVAD or BiVAD); duration of support and support intent.
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VADs can be broadly characterized by duration of support (temporary vs durable), design (pulsatile vs continuous flow), or site of implantation (paracorporeal, intracorporeal, or intravascular).
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Currently intracorporeal CF devices are generally considered in children >15-20kg and use has been increasing over the last decade. The Berlin EXCOR is used mostly in children <20kg. The paracorporeal continuous flow devices are used in patients that may recover, those that need BiVAD support and as a BTT in some high-risk populations such as small children with CHD.
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TAH can be used in children but has mainly been used in unique situations such as complex CHD and transplant graft failure.
Operative management
Optimal surgical technique depends on the device and the patient's unique characteristics. In children, challenges due to anatomic and pathophysiologic variations remain.
Surgical Considerations: Achieving an ideal inflow configuration is vital and dependent on the patient's anatomy. When positioning an apical cannula, regardless of whether it is an intracorporeal or paracorporeal VAD, the cardinal rule is to position the inflow cannula parallel to the interventricular septum, facing the systemic AV valve. With dilated ventricles, apical cannulation is less challenging; however, in non-dilated hearts such as restrictive, hypertrophic cardiomyopathy or CHD this can be more difficult. In these cases, strategies to accommodate the LV apical cannula including extended LV myectomy, mitral valve leaflet/apparatus excision and even prosthetic valve removal have been successfully reported.
However, for the restrictive and hypertrophic diagnoses apical cannulation may not ideal due to contraction around the inflow cannula compromising flow. Alternatively, an atrial cannulation may be considered. This strategy also has the benefits of avoiding a ventriculotomy, and the use of CPB.
The next challenge can be the outflow graft anastomosis to the ascending aorta due to the length and diameter of the vessels. Several modifications have been reported including the interposition of a vascular graft between the outflow cannula tip and the aortic wall or the innominate artery.
In general, the outflow graft cannula should be positioned as proximal as possible to aid with future transplantation; but making sure it does not impinge on the right ventricle especially with the EXCOR cannulae. Therefore, it should be placed about 45 degrees off the anterior surface of the aorta to the patient's right.
Pediatric alternatives to inflow implantation sites have include utilization of the diaphragmatic surface of the LV.
Such a technique may not be suitable in small pediatric hearts because of the risk of posterior descending coronary artery injury with the sewing ring and/or sutures.
Placing the pump in the pocket requires relocation of the LV apex medially and caudally, which orients the inflow cannula in a more vertical plane, parallel to the interventricular septum.
For RVAD placement, there are three sites for potential implantation: (1) the right atrium (standard site for EXCOR), (2) the diaphragmatic wall or (3) the free wall of the RV. The location depends on the device and cannulas selected. The EXCOR cannulas are tunneled through the skin and secured on the RA free wall directly opposite the tricuspid valve. For all implant sites, correct orientation of the inflow cannula is crucial to ensure unobstructed flow into the pump. The outflow graft is tunneled through the skin and is anastomosed (with or without a graft extension) to the pulmonary artery.
Driveline and cannula exit sites are important to plan before incision. For the EXCOR, the LV apical cannula must exit at a few cm below the left costal margin at or lateral to the mid-clavicular line. The LVAD arterial outflow cannula exits a few cm below and to the right of the xiphoid process. An RVAD outflow cannula to the pulmonary artery would be to the left of the midline and the inflow cannula would exist to the right of the LVAD aortic cannula. For proper connection the cannula have to cross either outside the body or within the chest. The latter is rarely done and is in not practical in those less than 10kg. The crossing of the outflow cannulae externally on the upper abdominal wall results in the LVAD EXCOR pump laying upside down (blood side up) compared to the right pump. At least several cm of skin should be preserved between adjacent cannulae exit points to prevent erosion and breakdown. Furthermore, the Dacron cuff on each cannula should extend at least 1 cm beyond the skin exit site to allow for tissue in growth.
There are times when concomitant surgery must occur. The most common is aortic and atrioventricular (AV) valve repair. Presence of significant aortic incompetence should be addressed with replacement, repair or over-sewing at the time of VAD implantation regardless of chosen device. AV valve stenosis has to be avoided when implanting the inflow cannula into the ventricle but there are mixed reports of treatment of AV valve regurgitation including AV valve repair, replacement or removal.
In all pediatric VAD patients, determination of the presence of intra and extracardiac shunts is required.
Outcomes following implantation of mechanical circulatory support in adults with congenital heart disease: an analysis of the interagency registry for mechanically assisted circulatory support (INTERMACS).
While some surgeons leave a small Patent Foramen Ovale (PFO) or atrial fenestration intentionally, especially in the Fontan patients, larger intracardiac communications should be closed either percutaneously or at time of VAD placement to avoid cyanosis.
Perioperative antimicrobial prophylaxis should be targeted to skin flora as the most likely contaminants of the surgical site. Limited data are available in pediatric VAD
Infectious complications of ventricular assist device use in children in the United States: data from the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs).
and no randomized data exists looking at surgical prophylaxis for pediatric VAD. Recommendations are based on available guidelines, including ISHLT, for adult VAD therapy.
When evaluating for a durable VAD it is important to review cardiac morphology and physiology data, including the presence of shunts, collateral vessels, and the location and course of great vessels.
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In pediatric patients with residual shunting, shunt closure (exceptions may exist in the Fontan patients) should occur at the time of VAD implant.
Post-operative hemodynamic goals
Device settings should be optimized in the operating room with both TEE and hemodynamic monitoring before and after chest closure. After returning to the ICU, the primary postoperative goals are to obtain sufficient systemic perfusion and maintain normal systemic and venous pressure while avoiding VAD-related complications. Establishing appropriate device settings requires identification of physiologically appropriate CO goals as well as careful assessment of imaging and hemodynamic parameters. In biventricular physiology, the goal CI is commonly 2-3 L/min/m2. In the case of single ventricle physiology, a much higher CO goal to achieve pulmonary venous unloading and optimal end-organ perfusion may be needed.
For the EXCOR, pump parameters should be manipulated to maintain a full device fill and ejection with each cycle. The maximal output of the device is calculated by the product of the device size (stroke volume) and set rate. The actual output is generally less, but difficult to accurately estimate given the volume of a half sphere is related to the radius to the third power. Several strategies targeting both the patient and the device can be employed to increase fill and thus increase output when desired. Decreasing the percent systole, the rate and diastolic pressure will increase the time spent in diastole and thus device filling, but this must be balanced by a commensurate increase in systolic pressure to ensure full device emptying. The broad availability of digital photography/video, particularly slow-motion, has emerged as a useful tool for assessment/troubleshooting.
For all of the CF devices, optimizing CO must be accomplished by optimizing preload and afterload while simultaneously preventing excessive leftward interventricular septal shift. Each pump is developed to function within a given range of power consumption for a given impeller/rotor set speed. When the relationship of these indices falls outside of that which is expected, an underlying etiology should be sought (excessive/ineffective pump speed, device thrombosis, device malfunction, etc.). Patient management should take into account the interaction between native cardiovascular system, physiology and device function. Though each device intrinsically has a unique pressure-flow response (H:Q) curve, all are innately sensitive to afterload. During diastole there is a large difference in pressure across the pump and therefore lower flow, while during systole the differences is smaller producing a higher flow state.
For BiVAD support, an imbalance can occur in flow of the pulmonary versus systemic circulation resulting in venous congestion upstream from the relatively under-supported circuit. As such, when RVAD output overwhelms that of LV support, pulmonary edema ensues. Alternatively, when LVAD support is in excess of RVAD support, hepatic, renal and digestive dysfunction may become apparent. Once biventricular support is balanced and unobstructed, the hemodynamic management is focused on avoidance of hypo- or hypervolemia and afterload reduction to achieve a normal CO.
Key Points
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EXCOR settings should be targeted to allow a full fill and ejection with each cycle, use of digital image capture with slow-motion can aid in the assessment of membrane movement.
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CF device support parameters should be individualized to physiologic support needs and optimized not only through changes in parameters but also manipulation of afterload and preload.
Anticoagulation management
Post-operative Hemostasis: Bleeding is a significant issue following VAD implantation. The risk for bleeding stems from disturbances in the coagulation profile in pediatric patients and are related to developmental hemostasis, heart failure cachexia, liver dysfunction, and coagulation factor/platelet consumption. Coagulation deficits including thrombin generation factors, adhesive proteins concentrations [fibrinogen and Von Willebrand factor (VWF)], and platelet function should be regularly assessed and normalized to stop bleeding. Thromboelastography (TEG) and ROTEM can diagnose specific deficits in the early post-operative phase. Factor deficiencies resulting from blood and volume administration must be avoided through concurrent use of blood products, coagulation concentrates, and other hemostatic agents guided by functional hemostatic evaluations. Anticoagulation may be considered only after achieving hemostasis.
Developmental hemostasis: There are qualitative and quantitative changes in hemostasis from fetal to adult life making following adult anticoagulation protocols difficult in pediatric VAD. For example, infants and adults may share similarities in size and numbers of platelets but their pharmacological responses vary. The response to agonists may be decreased in neonatal platelets compared to adults and more so in pre-term infants. However, despite blunted reactivity, infants compensate by having higher levels of VWF and multimers in addition to the higher hematocrit.
As well, in the neonate, the plasma levels of pro-coagulant factors (which are produced by the liver), including the vitamin-K dependent ones, are at approximately 50% of what an adult may have. This reflects the differences in neonatal and adult partial thromboplastic time (PTT).
Furthermore, the concentration of antithrombin (AT3), protein C and S are lower in infants compared with adults, and infants have a reduced ability to break down fibrin due to decreased levels of plasminogen. The changes in AT3 concentrations in neonates have led to difficulty with titration of heparin.
Anticoagulation and Antiplatelet Therapy: Historically, unfractionated heparin (UFH), low molecular weight heparin (LMWH) and vitamin K antagonists (VKA) have been the standard of care for paracorporeal and intracorporeal VADs in children.
However, there has been a shift towards increased use of direct thrombin inhibitors (DTI), namely bivalirudin, for anticoagulation, especially in the setting of paracorporeal VAD support.
Centers have also reported modification of the traditional antiplatelet therapy, with weight-based dosing of anti-platelet drugs in paracorporeal PF devices being associated with lower stroke rate.
Monitoring of anticoagulation and antiplatelet therapy remains a challenge, with limitations surrounding the consistency and interpretability of all laboratory tests. UFH can be titrated using activated prothrombin time (aPTT) or anti-Xa level. LMWH is titrated to anti-Xa levels, while VKA is monitored via International Normalized Ratio (INR) with device specific ranges.
In pediatrics, antiplatelet titration used to be heavily dependent upon Thromboelastography (TEG) with platelet mapping (TEG PM), however recent studies have demonstrated less dose response correlation with platelet mapping.
VerifyNow and Platelet Function Analyzer-100 (PFA-100) have been used to assess antiplatelet agent resistance; however these have yet to be validated in a pediatric population.
Effect of inflammation and infection on anticoagulation: Due to the shared nature between inflammation and anticoagulation, derangement of the normal coagulation function can occur during infection/inflammation. There are several markers of inflammation that can be used clinically including white blood cell counts, platelet counts, C-reactive protein, fibrinogen, and the presence of fevers, though it is not clear which marker is associated with the greatest likelihood of a bleeding or clotting complication. From a practical standpoint, the presence of fevers (in the absence of infection), elevated C-reactive protein levels, and elevated fibrinogen levels may lead to a change in anticoagulation or the addition of corticosteroids.
While the data are limited regarding the efficacy of this therapy, there are small single-center studies that suggest steroids do decrease markers of inflammation and may decrease the incidence of stroke in patients on EXCOR support.
In North America, there is a shift towards the use of DTI therapy for paracorporeal VAD support in children.
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In EXCOR patients, post-VAD inflammation may increase the risk of thrombosis, bleeding and stroke and steroids have been used in small single center cohorts to treat the inflammatory state in an attempt to decrease the incidence of stroke.
Adverse events
See Table 2 from Pedimacs report for common adverse event rates.
Infection: Infection remains a significant complication following implant of VADs. These infections are grouped according to ISHLT infection guideline nomenclature
Infections account for about 17% of all the adverse events (AE) with these events more commonly occurring >3 months post implant and accounting for nearly 1 out of 3 of readmissions following discharge.
Infectious complications of ventricular assist device use in children in the United States: data from the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs).
Infectious complications of ventricular assist device use in children in the United States: data from the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs).
Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)-defined morbidity and mortality associated with pediatric ventricular assist device support at a single US center: the Stanford experience.
While early reports suggested that infection was not associated with decreased survival, recent data from Pedimacs suggests an increased mortality with infection in patients on CF devices.
Infectious complications of ventricular assist device use in children in the United States: data from the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs).
In the Pedimacs data, 77% of infectious AEs were treated with intravenous antibiotics, 11% with oral therapy and 8% required both surgical and antimicrobial therapy.
Infectious complications of ventricular assist device use in children in the United States: data from the Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs).
Adult-focused recommendations suggest management be based on the site and extent of the infection with consideration for secondary prophylaxis in some patient awaiting transplantation.
Right Ventricular Failure (RVF): RVF is manifested by elevated CVP, liver dysfunction, ascites, and renal injury. It usually occurs within 2 weeks of LVAD implant and is associated with both morbidity and mortality.
In adults, early RVF is defined as use of inotropes > 14 days, inhaled nitric oxide > 48 hours or unplanned RVAD. Incidence of early RVF in adults with CF-VADs is 15% to 40% but may be lower in children.
Incidence and echocardiographic predictors of early postoperative right ventricular dysfunction following left ventricular assist implantation in paediatric patients.
Preoperative risk stratification of right ventricular function utilizing cardiac magnetic resonance imaging compared with echocardiographic and hemodynamic parameters.
Aggressive pre-operative management of patients with RV dysfunction should focus on diuresis (goal CVP < 15 mmHg), institution of milrinone ± epinephrine for contractility, and pulmonary vasodilators to reduce RV afterload.
Intra-operatively, TEE monitoring of RV function should occur during LVAD implant.
Strategies to preserve RV function include: maintenance of adequate blood pressure, avoidance of pulmonary vasoconstriction and use of pulmonary vasodilators, use of continuous ultrafiltration during bypass, minimization or avoidance of cross clamp time, judicious use of blood products, arrhythmia control, consideration of delayed sternal closure, and maintaining the septum in a midline position.
Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.
Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assist device.
Outcome of unplanned right ventricular assist device support for severe right heart failure after implantable left ventricular assist device insertion.
Such short-term RV mechanical support options include paracorporeal CF VADs, percutaneous VAD, and ECMO; long-term RV support includes biventricular durable intracorporeal CF, TAH, or PF VAD devices.
Post-operatively, signs of RVF include decreased LVAD flow, suction events and decreased CO, acute kidney injury, and hepatic dysfunction. Management should incorporate aggressive use of pulmonary vasodilators as well as inotropes for RV CO support and avoidance of bradycardia until RA pressures are near normal. RV preload should be optimized with diuresis or hemodialysis to maintain CVP < 15 mmHg. Maintenance of sinus rhythm should be aggressively pursued.
Pump thrombosis (PT): PT is a less common but a significant complication of VAD therapy. It results from a variety of patient and pump factors and can develop slowly over time or have a rapid onset. The definitions and recognition of PT vary by device type with the current EXCOR pumps allowing visual inspection and intracorporeal pumps requiring a combination of abnormal VAD parameters, lab values consistent with hemolysis or symptoms of HF; with conformation only occurring if the pump is removed. Symptoms of hemolysis can include scleral icterus, dark urine (hemoglobinuria), and fatigue with signs including one or more of the following: elevated serum Lactate Dehydrogenase (LDH) (most sensitive marker), elevated plasma free hemoglobin, and low haptoglobin.
Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device.
Outcomes of pediatric patients supported with continuous-flow ventricular assist devices: a report from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Adverse events in children implanted with ventricular assist devices in the United States: data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
These algorithms focus on both medical and surgical interventions, with medical management including augmentation of anticoagulation (ex: Heparin or Bivalirubin) or antiplatelet agents (oral or intravenous), use of thrombolytic therapy and surgical management including pump exchange, heart transplant (HT), or explantation.
The choice between medical and surgical management depends on device type, stage of pump thrombosis, clinical presentation and potential complications of treatment. As there are few reports in children, it is unclear whether these strategies are applicable to pediatrics. One potential approach in pediatrics is to initiate heparin or Bivalirudin with rising LDH with or without changes in pump parameters. If no response and ongoing increases in LDH with changes in the pump parameters, in some institutions, low dose systemic tPA could be considered if no contraindications exist.
Lastly, if there are contraindications to tPA, evidence of rapid progression or no response to any of the above treatments, pump exchange should be considered.
In some institutions pump exchange occurs without a trial of tPA.
Neurological Events and Stroke: Device-related neurological events (NE) as defined by INTERMACS include: cerebrovascular accidents (CVA), seizures, encephalopathy, asymptomatic neuroradiological findings, confusion and extra-axial bleeding. Using this definition, NE comprise 12% of all adverse events and tend to occur early (23% within 3 months vs 5% thereafter).
Adverse events in children implanted with ventricular assist devices in the United States: data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
NE are more common in PF VADs (early 19.6 and late 5.6 events per 100 patient-months) vs. CF VADs (early 4.1 and late 0.7 events per 100 patient-months). However, patient characteristics differ between those receiving PF vs CF devices and in turn event rates are likely not solely related to device type. Ten percent of patients with intracorporeal CF devices had strokes, compared to 24% among paracorporeal CF and 21% among PF devices with most being ischemic.
Outcomes of children supported with devices labeled as "temporary" or short term: a report from the Pediatric Interagency Registry for Mechanical Circulatory Support.
The ACTION Network has recently undertaken a multi-center quality initiative (QI) to decrease stroke rates through use of standardized blood pressure goals, meticulous anticoagulation including DTI and improved communication between teams.
Additionally, VAD-related stroke management has challenges in pediatrics due to lack of standardized protocols. The ACTION Network has recently developed a stroke management bundle aimed at developing algorithm for pediatric stroke management. This emphasizes early recognition of stroke symptoms as critical, urgent neurological evaluation including a non-contrast head CT (within 30 minutes). If non-contrast head CT is negative but neurological symptoms persist, consideration should be for a CT angiogram. Institution of neuroprotective measures, intracranial pressure monitoring and potential interventions including thrombectomy or cranial decompression may be considered. In setting of ischemic stroke with evidence of vessel occlusion and large territory involvement, thrombectomy or intravenous tPA may be potential options for intervention.
Ferriero DM, Fullerton HJ, Bernard TJ, et al. Management of stroke in neonates and children: a scientific statement from the American Heart Association/American Stroke Association. Stroke.2019;50:e51–e96.
For patients with paracorporeal VAD, pump exchange should be considered if there is evidence of a clot. Anticoagulation management after VAD-related CVA is challenging. If invasive interventions are being considered, or for large territory ischemic strokes with high risk for hemorrhagic conversion, holding and potentially reversing anti-thrombotic therapy should be discussed. In setting of hemorrhagic stroke, if bleeds are small without neurological deficits, antithrombotic therapy should be held and resumed if stable neuroimaging and neurological exam. However, if there is interval expansion or large hemorrhagic involvement, antithrombotic therapy should be held and potentially reversal. Timing of re-initiation of antithrombotic therapy should be discussed among care team with consideration of repeat CT after initiation.
Bleeding : Bleeding is a major complication of VAD implantation and affects approximately 30% of pediatric patients.
Outcomes of children implanted with ventricular assist devices in the United States: first analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Adverse events in children implanted with ventricular assist devices in the United States: data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
The highest hazard for bleeding is in the immediate perioperative period when patients are extremely susceptible from suture lines and dissection planes.
Outcomes of children implanted with ventricular assist devices in the United States: first analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Adverse events in children implanted with ventricular assist devices in the United States: data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Bleeding is diagnosed when chest tube output is excessive and drops in hemoglobin necessitate transfusion. Bleeding can lead to pericardial tamponade when blood is not adequately evacuated via chest tubes. In LVAD patients, the initial clinical presentation of pericardial tamponade is typically an increase of CVP, followed by a decrease in LVAD flow (depending on the amount of RA/RV compression). As a consequence, blood pressure is usually decreased and frequently vasoactive substances have to initiated or increased. Other clinical signs for the impaired hemodynamic state are decrease in urine output and rise of serum lactate. The clinical presentation of tamponade in BiVAD patients can be very vague. Often, only an increase of CVP is initially observed which can early on be accompanied by a decrease of urine output (due to elevated CVP). Adequate hemodynamics can be obtained for a long time, depending on adequate volume replacement and VAD flow only decreases when venous return is severely compromised by compression. The threshold for surgical revision usually is persisting chest tube output despite normalization of coagulation parameters. Hemodynamic instability or tamponade should prompt immediate surgical exploration.
The hazard for bleeding decreases with increasing support times.
Outcomes of children implanted with ventricular assist devices in the United States: first analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS)-defined morbidity and mortality associated with pediatric ventricular assist device support at a single US center: the Stanford experience.
Adverse events in children implanted with ventricular assist devices in the United States: data from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
While perioperative bleeding usually originates from areas affected by the VAD implantation, late bleeding events typically affect other regions and are a consequence of medication levels and vWF degradation that is a result of VAD induced blood trauma. The most frequent source of late bleeding is the gastrointestinal tract, although less frequent than the adult population.
Support strategies for unique pediatric populations
CF VAD in small patients: The encouraging outcomes in adult VAD technology have had a profound impact on its use in children. In children, with a weight >15-20 kg requiring VAD, the use of an implantable LVAD may be feasible with results that are non-inferior to the extracorporeal devices,
Outcomes following implantation of mechanical circulatory support in adults with congenital heart disease: an analysis of the interagency registry for mechanically assisted circulatory support (INTERMACS).
Outcomes of children implanted with ventricular assist devices in the United States: first analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Outcomes of pediatric patients supported with continuous-flow ventricular assist devices: a report from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Outcomes following implantation of mechanical circulatory support in adults with congenital heart disease: an analysis of the interagency registry for mechanically assisted circulatory support (INTERMACS).
Outcomes of children implanted with ventricular assist devices in the United States: first analysis of the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
The limited thoracic space might not be large enough to ensure proper position of an intra-corporeal device. Distortion of the rotor housing can position the inflow cannula in a plane that significantly increases the risk of inadequate drainage, suction events and/or pump thrombus formation. If necessary the pump housing may be placed in a pre-peritoneal pocket fashioned by dividing the left diaphragm anteriorly
or to allow the device to sit within the left pleural cavity, caudal to the left lower lobe and posterior to the diaphragm at the costo-diaphragmatic angle. In smaller patients, not only the angle of the inflow cannula, but its depth in the ventricular cavity should be considered. If placed in a small heart, the tip of the inflow cannula may approach the mitral valve, which could either impede mitral valve function or, importantly obstruct the inflow cannula. Therefore LV apex to mitral valve distance must be precisely measured on preoperative imaging.
Patients with MD are often not candidates for HT because of the progressive nature of their multi-system disease, affecting pulmonary, neurological functioning and mobility. Some centers have reported the use of DT VADs for medically-resistant HF in these patient groups.
Implantation of the HeartMate II and HeartWare left ventricular assist devices in patients with Duchenne muscular dystrophy: lessons learned from the first applications.
Chemotherapy-Induced Cardiomyopathies (CCMP): Improvements in oncologic therapies has increased life expectancy and cure rates for many types of cancer. The cardiotoxicity risk of many chemotherapeutic regimens are well documented.
Cardiotoxic effects of chemotherapy: A review of both cytotoxic and molecular targeted oncology therapies and their effect on the cardiovascular system.
American Heart Association Congenital Heart Defects Committee of the Council on Cardiovascular Disease in the Young CoBCSCoC and Stroke Nursing CoCR. Long-term cardiovascular toxicity in children, adolescents, and young adults who receive cancer therapy: pathophysiology, course, monitoring, management, prevention, and research directions: a scientific statement from the American Heart Association.
VADs have been used for DT in patients with CCMP, or for BTT in patients with sustained remission. Pediatric data is limited and consistent with this being an uncommon indication for VAD therapy or HT.
Case report and review of the literature: the utilization of a ventricular assist device as bridge to recovery for anthracycline-induced ventricular dysfunction.
Cancer recurrence and mortality after pediatric heart transplantation for anthracycline cardiomyopathy: a report from the Pediatric Heart Transplant Study (PHTS) group.
Increased need for right ventricular support in patients with chemotherapy-induced cardiomyopathy undergoing mechanical circulatory support: outcomes from the INTERMACS Registry (Interagency Registry for Mechanically Assisted Circulatory Support).
Considerations including the increased risks related to RV dysfunction, bleeding and sternotomy after radiation therapy should be noted prior to VAD implantation.
Increased need for right ventricular support in patients with chemotherapy-induced cardiomyopathy undergoing mechanical circulatory support: outcomes from the INTERMACS Registry (Interagency Registry for Mechanically Assisted Circulatory Support).
Outcomes of pediatric patients supported with continuous-flow ventricular assist devices: a report from the Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS).
Experience is limited using VAD and/or TAH in ACHD patients as a bridge to transplant. Overall, <1% of all VADs in adults are implanted in ACHD patients. Nevertheless, ACHD patients spend more time awaiting HT
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