Management of long-term mechanical circulatory support devices

INTRODUCTION — Continuous flow ventricular support devices (used primarily as left ventricular assist devices [LVADs] and less frequently for biventricular support [BiVAD]) are increasingly used for the management of patients with end-stage heart failure (HF; ie, stage D, refractory HF requiring specialized interventions) both as a bridge to transplantation and as destination (or permanent) therapy [1-4]. LVADs have been shown to prolong survival in this clinical setting [5-7], but there are several complications associated with mechanical circulatory support device (MCSD) therapy. The postoperative course is complicated by frequent readmissions for bleeding, infection, pump thrombosis, right HF, and device malfunctions that require proper attention and management.

In this topic, we will review ventricular assist device complications and long-term outpatient management, focusing on care of patients with continuous flow devices. The most commonly used devices today are HeartWare (HW) and HeartMate 3 (HM3).

The evaluation and indications for durable MCS device placement are discussed separately. (See "Treatment of advanced heart failure with a durable mechanical circulatory support device".)

OUTPATIENT FOLLOW-UP

Physical examination — Continuous flow devices greatly alter the physical exam in supported patients. This presents a major challenge to clinicians and first responders in assessing these patients. Continuous flow left ventricular assist devices (LVAD) supported patients frequently have no palpable pulse and blood pressure may not be measurable by auscultation. Heart sounds are obscured by the hum of the device. Additionally, high placement of the external driveline can impede examination of the liver and assessment of hepatic congestion.

Underlying heart rate and rhythm are best assessed by precordial auscultation or electrocardiogram (ECG).

Given the reduced arterial pulse pressure seen in these patients, blood pressure is best estimated using a Doppler ultrasound probe and sphygmomanometer (generally brachial) [8]. Doppler pressure measurements fall between arterial line systolic pressure and mean arterial pressure, tending to be closer to systolic pressure (eg, average Doppler ultrasound measurements 4.1 mmHg lower than systolic pressure and 9.5 mmHg higher than mean arterial pressure in one small series [9]). Doppler measurements of 70 to 80 mmHg are ideal while Doppler pressures above 90 mmHg warrant therapeutic intervention. Newer devices for blood pressure measurement such as the Terumo Elemano blood pressure monitor are also clinically useful [10]. The Elemano device uses double-cuff oscillometric slow deflation technology with results correlating well with the arterial line blood pressure with minimal underestimation of systolic pressure (on average 0.3 mmHg lower) [9]. The device is easy to use and can be used for home blood pressure monitoring. The HeartMate 3 (HM3), the newest centrifugal pump, is programmed to slow down every two seconds and then return to the programmed speed. This can generate an artificial pulse while preventing stasis in the device. The presence of this intermittent pulse may facilitate measurement of blood pressure, but this has not been validated.

Another important element of the physical exam in mechanical device patients is assessment of the percutaneous driveline or lead for infection or damage. Percutaneous line infection continues to occur with all current devices. It is important to stabilize and anchor the driveline to avoid trauma and potential infection. Direct inspection of the driveline site for erythema, swelling, and/or purulent discharge should be part of every clinician encounter. Culture of any drainage is recommended, and Gram stain is helpful for demonstrating neutrophils and infecting bacteria [11]. Abnormal swelling of the region surrounding the driveline site should be assessed by ultrasound to assess the presence, extent, and characteristics (inhomogeneity) of any fluid collections [11]. Percutaneous lead damage is a frequent cause for device exchange. The driveline should be inspected for tears in the outer casing or tears at the connecting sites which can expose the internal wires. Repair of the driveline with safety clamps or reinforcement with tape may occasionally be needed.

Electrocardiogram — An ECG should be obtained to evaluate the heart rate and rhythm. A high index of suspicion is appropriate for patients with vague symptoms since sustained ventricular tachycardia or ventricular fibrillation in a patient supported by a VAD may present merely as fatigue. Sustained (particularly incessant) ventricular arrhythmias generally precipitate worsening right HF and therefore require prompt attention [12]. Cardiac auscultation can provide evidence of continued pump function with the audible whirl of the axial or centrifugal pumps [13], which is particularly helpful as a means of identifying a functioning device in patients with acute mental status change.

Echocardiography — Assessment of cardiac function, optimization of device settings, and exclusion of chronic complications such as development of aortic regurgitation or thrombus formation are best achieved with echocardiograms. Though a routine echocardiogram is not required at each visit, an echocardiogram should be performed at regular intervals and is indicated if there are unexplained symptoms of fatigue, device alarms, defibrillator discharges, dizziness, or increased right HF [12-14]. Key features of the echocardiographic exam include assessment of ventricular size, interventricular septal position, valvular function (eg, mitral regurgitation and aortic valve opening), and assessment of inflow and outflow abnormalities. (See 'Device interrogation' below.)

Device interrogation — Device mechanical function is evaluated at each visit by interrogating the device controller. For all current devices, alarm alerts can be reviewed along with flow estimates, pump power, and pump speed [13,14].

●Flow estimates for the HeartMate II (HMII) and HM3 devices range from 3 to 10 L/min with normal flow in the range of 4 to 7 L/min. The flow range for the HeartWare (HW) device is 2 to 10 L/min with a normal range of 3.5 to 7 L/min.

●Pump power is correlated with device flow, and an increase in flow will increase power; however, increases in pump power without changes in pump speed, volume status, or afterload reduction may indicate device malfunction from thrombus formation. The average pump power six-month post-device implantation for the HMII is 6.8±1.2 W with a normal range of 5 to 8 W [13]. For the HM3, the power range is usually between 3 and 4 W. For the HW, the normal power range is 3 to 7 W.

●Pump speed is adjusted with the aid of echocardiography to allow adequate filling of the LV without development of suction (excessive emptying) [12]. The interventricular septum should be midline with some aortic valve opening to prevent the development of aortic insufficiency and thrombus formation, but the optimal frequency of aortic valve opening remains uncertain. No more than mild mitral regurgitation should be observed [13,14]. The normal pump speed ranges for HMII, HM3, and HW are respectively 8000 to 10,000, 5000 to 6000, and 2400 to 3200. Suction events are discussed further separately. (See "Emergency care of adults with mechanical circulatory support devices", section on 'Low flow'.)

●For the HMII and HM3 devices, the pulsatility index (displayed as Pulse Index on the monitor) is calculated by averaging the flow pulses seen with ventricular contraction over a 15-second period. The pulsatility index is inversely related to the amount of assistance provided by the pump and, for the HMII, generally averages 5.0±0.9 [13]. Patients with improved LV function such as occurs with exercise, myocardial recovery, or addition of inotropes will show an increase in the pulsatility index. Low pulsatility index indicates either low intravascular volume or minimal native cardiac function.

ANTITHROMBOTIC THERAPY — Patients supported by ventricular assist devices (VADs) need to be treated with anticoagulant and antiplatelet agents to reduce the risk of thrombotic complications such as device thrombosis and embolic stroke. Since these patients are also at risk for bleeding complications, anticoagulation should be carefully timed and titrated, and the following measures are suggested [12,13]:

●Antiplatelet and anticoagulant medication should generally be withheld for four to seven days before the left ventricular assist device (LVAD) is implanted [13].

In patients who have undergone recent stent implantation, early discontinuation of dual antiplatelet therapy is contraindicated due to the risk of stent thrombosis (see "Long-term antiplatelet therapy after coronary artery stenting in stable patients"), so LVAD implantation should be delayed if possible.

●Earlier practice limited immediate postoperative anticoagulation with intravenous heparin to patients with specific additional indications for anticoagulation such as atrial fibrillation, prior embolic stroke, LV thrombus, left atrial thrombus, or LVAD low flow [13]. With the later observation of an increase in early pump thrombosis [15] (see 'Thrombosis' below), we suggest use of intravenous heparin in all patients early after LVAD implantation (eg, postoperative day one or two) as recommended in the 2013 International Society for Heart and Lung Transplantation guidelines once the chest tube drainage is no longer sanguineous and there is no other evidence of bleeding [12].

●Vitamin K antagonist therapy (eg, warfarin) as well as aspirin (81 to 325 mg daily) is initiated after postoperative bleeding has stopped and chest tubes have been removed, typically days two to three postoperatively [12]. The goal international normalized ratio (INR) in clinical trials and from the manufacturer for the HeartMate II (HMII) is 2.0 to 3.0 [12]. Due to the frequency of bleeding complications, some have suggested a target INR range of 1.5 to 2.5 for the HMII [13]. However, due to later reports of higher-than-expected rates of pump thrombosis, we suggest a target INR of 2.0 to 3.0 for the HMII. (See 'Thrombosis' below.)

EXERCISE PERFORMANCE

Exercise parameters — Exercise capacity in patients supported by left ventricular assist devices (LVADs) is generally monitored by six-minute walk distance.

The exercise physiology of patients supported by LVADs is unique. Patients with HF have limited exercise capacity due to both central and peripheral effects. Unlike the earlier pulsatile LVAD devices, which had an automatic fill mode that ejected faster with an increase in pump filling and thus were preload responsive, the continuous flow LVADs work with a fixed pump speed that does not change with exercise. The speed is selected at rest to optimize unloading of the ventricle and to prevent excessive emptying (known as suction events) that could result in hypotension and arrhythmias. Maximum cardiac output of these devices is approximately 10 to 12 L/min. Additional cardiac output can be provided by the native heart. However, the right ventricle is unsupported. Also, long-term complications associated with LVADs such as aortic valve fusion and aortic regurgitation reduce the ability of the native heart supported by LVAD to improve exercise capacity [13].

Despite these limitations, rest and exercise hemodynamic measurements in patients with continuous flow LVADs are improved with lower pulmonary arterial and pulmonary wedge pressures and higher cardiac output. However, peak Vo₂ following LVAD implantation averages only 12 to 17 mL/kg/min [16,17]. The exercise response of the HeartMate II (HMII) is comparable to that seen with the pulsatile HeartMate XVE, and some preliminary studies have shown minimal enhancement of peak Vo₂ following pulsatile or continuous flow device placement. A report on the hemodynamic response to exercise in patients supported by continuous flow LVADs demonstrated persistently impaired exercise capacity in patients with HMII and HeartMate 3 (HM3) devices [18]. Fick cardiac output at peak exercise was the parameter most predictive of Peak Vo₂. Electronic algorithms that modify pump response to increased workload are needed to improve cardiac performance with exercise.

Since improvement in peak Vo₂ has been limited, most studies have focused on using quality-of-life assessments or submaximal exercise testing with the six-minute walk test to evaluate the impact of device therapy. The HMII destination therapy trial (comparing continuous flow and pulsatile flow devices) demonstrated significant improvement in both quality of life and six-minute walk distance in the continuous flow device supported patients [7].

Cardiac rehabilitation — We suggest starting physical therapy in the early postoperative period. Stage D HF patients frequently come to surgery severely debilitated, bedbound, malnourished, and are often dependent on intravenous medications to support the circulation at rest. Following LVAD implantation, these patients become ambulatory and could benefit from intensive rehabilitation. Formal cardiac rehab programs post-LVAD have not been well described and most rehabilitation centers are unfamiliar with the operation of LVADs. Close collaboration between the device and rehabilitation centers is needed to develop successful rehabilitation programs. There are minimal data on the impact of aerobic training in these patients [19].

COMPLICATIONS OF VADS — Complications following ventricular assist device (VAD) implantation include bleeding both in the perioperative period and in the long term because of the need for pharmacologic anticoagulation and also because of the development of acquired von Willebrand disease (aVWD) in many patients [20]. They can also include acute and chronic right HF, device thrombosis, thromboembolism, infection, aortic regurgitation, ventricular arrhythmias, and hemolysis [21]. Possible technical problems can include malposition of the inflow cannula, kinking of outflow grafts, bend relief disconnection, cable damage, and device failure [21]. Evolving left ventricular assist device (LVAD) technology has reduced the risk of some complications (eg, infection, pump stoppage) but led to new complications (eg, aVWD).

Bleeding

Causes and sites of bleeding — Patients with VADs are at risk for bleeding in the perioperative period as well as following recovery from implantation of the device [22]. A US Food and Drug Administration (FDA) Safety Communication noted the risk of bleeding for the two LVADs approved by the FDA (the HeartMate II [HMII] and the HeartWare [HW]) [23]. In the HMII destination therapy trial, rates of bleeding requiring transfusions were 1.66 and 1.13 events per patient-year in the early and mid-trial groups [24].

Bleeding may occur from a leaky connection at the pump, from polyester grafts in the conduits (from inadequate preclotting, which is a procedure to seal the grafts), from mucosal surfaces (particularly gastrointestinal, including gastrointestinal arteriovenous malformations [AVMs] [25] (see "Angiodysplasia of the gastrointestinal tract")), and from intracranial vessels [13].

In the randomized trial of continuous versus pulsatile flow pumps, the leading cause of death in each group was cerebral hemorrhage [7], although the risk of hemorrhagic stroke may be decreasing with experience (eg, 0.07 events per patient-year in the early HMII destination therapy trial versus 0.03 events per patient-year in the mid-trial group) [24].

Bleeding in the perioperative period is frequently related to the coagulopathic effect of extracorporeal circulation during cardiopulmonary bypass (CPB), impaired coagulation due to hepatic congestion associated with end-stage HF, and treatment with anticoagulants. Perioperative hemorrhage continues to be problematic with the newer continuous flow pumps despite less traumatic surgical implantation than was the case with the bulkier pulsatile pumps.

Bleeding more than a week post-device implantation may be precipitated or exacerbated by required anticoagulant therapy in combination with the development of acquired von Willebrand syndrome (AVWS). (See "Acquired von Willebrand syndrome".)

von Willebrand factor (VWF) is a multimeric glycoprotein secreted by endothelial cells and platelets that promotes platelet adhesion and aggregation and stabilizes plasma coagulation factor VIII. The largest multimers of VWF are the most active forms of VWF. (See "Pathophysiology of von Willebrand disease", section on 'VWF functions'.)

Both second- and third-generation continuous flow devices can cause AVWS, probably due to the action of the rotary or axial flow pump, which generates high shear stress that may enhance proteolysis of large VWF multimers. The pathogenesis of AVWS with VAD therapy is likely similar to that in other clinical settings with high intravascular shear forces in which AVWS has been reported (eg, aortic stenosis). (See "Acquired von Willebrand syndrome", section on 'Cardiovascular disease'.)

Multiple series have identified AVWS in all analyzed patients receiving the HMII continuous flow VADs, with a high associated risk of bleeding [26-31]. The disorder resolves after removal of the VAD [27]. The bleeding is more frequent in older individuals [27]. Limited data are available on the risk of AVWS in patients with other devices. In one series, AVWS was not found in three recipients of the pulsatile HeartMate XVE [31], but in another study, AVWS was identified in all six patients implanted with a biventricular pulsatile device (Thoratec-PVAD) [30].

Evaluation for acquired VWS — All patients with continuous flow VADs are assumed to have AVWS and are not routinely tested. We test for AVWS in patients who have excessive bleeding in the setting of a VAD.

The clinical manifestations of AVWS are similar to inherited VWD and include easy bruising, skin bleeding, and prolonged bleeding from mucosal surfaces (eg, mouth, gastrointestinal tract). Females may experience heavy menstrual bleeding. Other observed bleeding complications include epistaxis, hematuria, mediastinal bleeds, and intracranial bleeds. Bleeding may arise from gastrointestinal lesions that might have otherwise been asymptomatic (eg, AVMs, gastritis, diverticulitis) [25]. Bleeding may also occur during invasive procedures.

The diagnosis of AVWS using assays for VWF antigen and activity is discussed in detail separately; we follow the same diagnostic algorithm used in other patients with suspected VWD (initial testing for platelet-dependent VWF activity, with subsequent testing depending on that result). (See "Acquired von Willebrand syndrome", section on 'Diagnostic evaluation'.)

Prevention and management of bleeding

Perioperative management — Anticoagulants and antiplatelet agents should generally be held for five to seven days prior to VAD placement, and patients should be screened preoperatively for coagulation abnormalities [22]. Platelet transfusions are used to keep the platelet count >100,000/microL. If warfarin anticoagulation has not been reversed, we wait until reversal; in an emergency, one could administer a reversal product (eg, prothrombin complex concentrate [PCC], vitamin K). (See "Management of warfarin-associated bleeding or supratherapeutic INR".)

Intraoperative measures to reduce the risk of excessive bleeding include minimizing CPB time, meticulous surgical technique to minimize bleeding and promote hemostasis, and transfusions as indicated (platelets, packed red blood cells, plasma, or whole blood) [13]. (See "Use of blood products in the critically ill".)

The risk of early postoperative bleeding can be reduced by avoiding too early and too aggressive postoperative anticoagulation as discussed above [13,22]. (See 'Antithrombotic therapy' above.)

Management of ongoing risk of bleeding — Patients with VADs who develop AVWS require special attention to bleeding risk when undergoing invasive cardiac and noncardiac procedures. Patients supported by continuous flow mechanical assist devices who undergo cardiac transplantation require significantly greater numbers of blood transfusions than those supported by pulsatile LVADs or medical therapy alone [27]. There are no data to support using lower pump speed rates as a way to minimize bleeding.

Blood pressure control is important to reduce the risk of an intracerebral bleed (and hypertension control may reduce the overall risk of stroke). Optimization of medical therapy may also be important, as use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers, digoxin, and high-dose omega 3 fatty acids have been reported to be beneficial in decreasing gastrointestinal bleeding in single-center studies [32-34].

Options for patients with recurrent gastrointestinal bleeding from angiodysplasia include endoscopic treatment, including coagulation or clips. If the bleeding site is not identified or if the AVMs are too numerous, then pharmacologic therapy may be considered, including use of octreotide, a small peptide that mimics somatostatin and has been used in the management of esophageal variceal bleeding as it lowers portal venous pressure. Alternatively, desmopressin can be tried, as it causes increased release of VWF from megakaryocytes and endothelial cells.

Thalidomide in low doses can be antiangiogenic and has been used. Some studies describe an altered ratio of angiopoietin-1 to angiopoietin-2 as potentially contributing to the development of AVMs [35], and thalidomide may be helpful in restoring the ratio [36]. Background anticoagulation therapy is adjusted, and, frequently, antiplatelet agents will be discontinued and the international normalized ratio (INR) target value will be lower. The definitive treatment is removal of the causative agent, which in the case of an implanted device is usually not possible unless there is an opportunity to proceed with cardiac transplantation. (See "Angiodysplasia of the gastrointestinal tract".)

For patients with bleeding or at risk of bleeding from an invasive procedure, the following interventions may be appropriate:

●Measures to increase levels of plasma VWF and treat bleeding in patients with AVWS include desmopressin (DDAVP), VWF concentrates, an antifibrinolytic agent, recombinant factor VIIa, and others. Decisions regarding which therapy to use depend on the degree and/or risk of bleeding and should be made in consultation with a hematologist. Responses to some treatments are likely to be short-lived due to ongoing proteolysis of VWF. (See "Acquired von Willebrand syndrome", section on 'Treatment of acute bleeding'.)

●Additional interventions to reduce the risk of intracerebral hemorrhage (eg, blood pressure control) should also be employed. (See "Risks and prevention of bleeding with oral anticoagulants", section on 'Approaches to risk reduction'.)

●If life-threatening bleeding occurs, it may be necessary to temporarily reduce, discontinue, and/or reverse anticoagulation. (See "Management of warfarin-associated bleeding or supratherapeutic INR", section on 'Serious/life-threatening bleeding' and "Heparin and LMW heparin: Dosing and adverse effects", section on 'Reversal'.)

●Platelet transfusion for those receiving antiplatelet therapies may also be helpful in treating severe bleeding. (See "Platelet transfusion: Indications, ordering, and associated risks", section on 'Platelet function disorders'.)

Thrombosis — Although the risk of thrombus formation is reduced by therapeutic anticoagulation, patients remain at risk for pump thrombosis, stroke, and other thromboembolic events in both the HMII and HW devices [21,22].

Risk factors for thrombus formation include:

●Inadequate anticoagulation

●Atrial fibrillation

●Hypercoagulable states

●Infection, which increases the risk of coagulation abnormalities leading to thrombus formation

One of the major results for the initial six-month report of the MOMENTUM 3 trial was the absence of pump thrombosis in HeartMate 3 (HM3) patients. This striking reduction in pump thrombosis with the HM3 device was observed in the final analysis of the 1028 patient MOMENTUM 3 trial, with 70 cases of suspected or confirmed pump thrombosis in the HMII group and only seven cases in the HM3 cohort [37]. Since the approval of the HM3 device in 2017 (bridge to transplantation or recovery) and 2018 for destination therapy, there has been a dramatic decline in the use of the axial flow pumps (HMII). In a 2020 INTERMACs report, only 2 percent of the LVADs implanted from January 1, 2019 through September 1, 2019 were HMII devices, while 78 percent were HM3 devices [38].

Pump thrombosis resulting in pump obstruction is associated with high mortality and can occur as an early or late complication. For continuous flow devices, rates for device thrombosis have ranged from 0.01 to 0.11 per patient-year [15,22,39].

The cause of pump thrombosis with the HMII device is uncertain, though it was postulated that thrombosis may arise from deposition of fibrin and denatured protein adjacent to the inflow bearing. Other possibilities include changes in practice patterns by clinicians such as lowering of target INR to 1.5 to 2.5, intermittent interruption of anticoagulation due to bleeding from AVWS, and discontinuing the practice of bridging patients early postoperatively with intravenous heparin while adjusting warfarin dosing [39-41].

Other hypotheses include inadequate platelet therapy, overestimation of the partial prothrombin time, abnormal angulation of inflow or outflow cannulas leading to reduced blood flow and bearing heating with negative effects on coagulation proteins, infection, right HF, use of erythropoietic factors, and/or other factors not yet identified [39,41].

Given these higher-than-expected rates of pump thrombosis, we suggest all patients with HMII devices receive early postoperative intravenous heparin with overlapping initiation of aspirin and a vitamin K antagonist (eg, warfarin) using a target INR of 2.0 to 3.0. We also suggest monitoring for pump thrombosis, including serial serum lactate dehydrogenase (LDH) levels. (See 'Antithrombotic therapy' above.)

The PREVENT trial endorsed the use of a combination of surgical implant techniques, anticoagulation, and pump management strategies to minimize the risk of pump thrombosis in 300 HMII patients [42]. The surgical approaches included creation of an adequately sized pump pocket located inferiorly deep and lateral, positioning the inflow cannula parallel to the septum, the outflow cannula to the right of the septum, the pump beneath the diaphragm, and fixating the pump to the diaphragm or chest wall to prevent migration. For anticoagulation, the protocol included early heparin administration in the absence of significant postoperative bleeding, as well as early initiation of warfarin (with INR goal of 2 to 2.5) and aspirin. For pump management, speeds below 8600 rpm were to be avoided with a goal of >9000 rpm with intermittent aortic valve opening. Maintenance of mean arterial blood pressure below 90 mmHg was recommended. Using these guidelines, the occurrence of pump thrombosis was reported as 4.8 percent at six months.

The diagnosis of pump thrombosis is suggested by the development of hemolysis and by changes in pump performance. There is a continuum of symptoms depending on the extent of clot with some patients asymptomatic while others present with severe HF with or without multi-organ failure. Clinical manifestations of hemolysis include red or reddish-brown urine, worsening renal function, elevated serum LDH (>1000) [15], decreased serum haptoglobin, and increased free plasma hemoglobin (see "Diagnosis of hemolytic anemia in adults"). The change in pump performance most suggestive of thrombosis is the development of marked transient increases in power consumption (power spikes) or gradual increase in power requirement of at least 2 Watts. When pump thrombosis is present, pump flow decreases and increased pump speed is required to maintain adequate flow.

Echocardiography performed at increments of LVAD speed is helpful in identifying pump thrombosis. Lack of decline in LV diastolic dimension with increasing pump speeds suggests obstruction to flow. An echocardiography ramp test for speed optimization and diagnosis of device thrombosis has been described [43].

Early pump obstruction generally requires immediate pump exchange or heart transplantation [15,21]. In the above report on increased rate of pump thrombosis, thrombosis was managed by heart transplantation in 11 patients (with one death) and by pump replacement in 21 [15]. In 40 patients with 40 thromboses not treated by transplantation or pump replacement, the actuarial mortality rate was 48.2 percent at six months after diagnosis of pump thrombosis.

Late pump thrombosis can sometimes be successfully treated with addition of intravenous heparin while chronic anticoagulation is intensified. Case reports have described thrombolysis using recombinant tissue-type plasminogen activator (rt-PA) or tirofiban. Pump exchange is required if pharmacologic therapy is not effective.

Hemolysis — Hemolysis following LVAD placement may occur due to device-related factors (eg, pump thrombosis, malposition of cannulae) or nondevice-related causes (eg, drug-induced hemolytic anemia) [21]. (See 'Technical problems and device failure' below and "Clinical presentation and diagnosis of heparin-induced thrombocytopenia" and "Drug-induced hemolytic anemia" and 'Thrombosis' above.)

Right heart failure — Right HF is a cause of major morbidity and mortality following LVAD placement. When an LVAD supports the left side of the heart and normal cardiac output is conducted via venous return to the right heart, the right ventricle sometimes fails since there is often underlying biventricular dysfunction. In addition, the LVAD tends to decrease LV pressure and size, which may lead to a distortion of the geometry of the right ventricle, resulting in septal bowing. This septal bowing can cause obstruction to right ventricular outflow as well as worsening right ventricular (RV) mechanics with decrease in RV stroke volume and an increase in tricuspid regurgitation. The incidence of right HF in the perioperative period following LV support varies from approximately 5 to 50 percent, depending on the definition used [13]. Some studies define right HF as the need for right ventricular mechanical support, whereas other studies define it as need for right ventricular mechanical support or extracorporeal membrane oxygenation (ECMO), or prolonged therapy with inhaled nitric oxide or intravenous inotropic therapy.

Predictors of RV failure in the perioperative period include hemodynamic and echocardiographic parameters such as RV stroke work index <250, right atrial pressure >15 mmHg, severe RV dysfunction on echocardiogram, renal insufficiency, hepatic dysfunction, elevated pulmonary vascular resistance, and reduced tricuspid annular plane systolic excursion (TAPSE <0.75 cm) (table 1). Although predictive models have been developed to estimate risk, there is no consensus on how best to predict early right HF and clearly no data on the development of chronic right HF [13,14,16].

Evaluation of patients with suspected right HF includes right heart catheterization and transthoracic echocardiography, which is useful as a guide for optimizing LVAD device settings to minimize septal bowing during device support [12,44-47]. Patients with RV failure may require hospitalization for treatment, which may include inotropic support or right ventricular mechanical support or ECMO [12].

Though the emphasis has been on early postoperative right HF, there are increasing reports of late onset right HF. Late onset right HF may result from continued progression of intrinsic right ventricular dysfunction, recurrent ventricular arrhythmias, progression of tricuspid regurgitation, pulmonary hypertension, or device malfunction or thrombosis [48]. Frequently, the patients are treated with diuresis with or without inotropic support. The presence of late right HF has been associated with poorer outcomes post-transplant.

Infection — Infection can occur in the pump, in the pump pocket, and around the driveline. Continuous axial flow pumps have smaller surface areas of foreign material, lesser pump movement inside the body, and smaller drivelines compared with the pulsatile pumps with consequent lower infection rates (eg, 0.37 versus 3.49 driveline infections per patient-year for the HMII versus HeartMate I [HMI] devices) [7]. However, driveline infection remains a significant problem late after device implantation. Patient education should emphasize the importance of meticulous lead and exit site care and lead immobilization to reduce the risk of infection [12,13].

Evaluation of MCS patients with suspected infection includes a complete blood count, chest radiograph, and at least three sets of blood cultures over 24 hours (with at least one from any indwelling central venous catheters) [12]. If cannula or driveline infection is suspected, work-up should include obtaining a sample for Gram stain, potassium hydroxide preparation, and routine bacterial and fungal cultures.

The ISHLT guidelines include criteria for identification of MCSD-specific infections and MCSD pocket infections [12].

Aortic regurgitation — Development of de novo aortic regurgitation has been observed in up to 25 percent of patients supported by a continuous flow device [47,49,50]. Aortic regurgitation occurs more frequently in those patients in whom the aortic valve remains closed (occurring in 42 percent of such patients in one series) than in those device patients with frequent aortic valve opening (occurring in 7 percent of patients in the same series) [47]. The development of significant aortic regurgitation decreases the efficacy of device support and some cases require aortic valve surgery. Patients who develop symptomatic aortic insufficiency post-VAD implant should be treated with an increase in pump speed. If the patient remains asymptomatic, the pump speed should be set to maintain intermittent AV opening under echocardiographic guidance. Pathology specimens at time of autopsy or explant of hearts at transplant have demonstrated fusion of aortic valve leaflets. The mechanism underlying the fusion of the valve leaflets is unclear.

Park’s central stitch (a simple central coaptation stitch) has been used to reduce aortic regurgitation in patients on continuous flow LVAD support who develop significant aortic regurgitation and some surgeons have proposed prophylactic use of this stitch at the time of device implantation to prevent this complication [51]. However, the efficacy of these approaches is not proven.

Technical problems and device failure — Device failure is another serious problem that can occur, generally late after device insertion. There can be failure of the external components (which can usually be replaced), or of the internal components (which can be life threatening). Device failure was far more common with the first-generation pulsatile pumps, as they had more moving parts. However, they did have a hand pump back-up system [52]. The second-generation axial flow pumps (eg, HMII) have only one moving part (the rotor). They are more durable with a much lower rate of device failure. However, the presence of bearings can lead to wear, tissue ingrowth, and thrombus formation. The third-generation magnetic levitation pumps have no bearings to wear out and are expected to be much more durable.

Pump stoppage of a continuous flow MCSD requires emergency expert medical care [12]. Definitive therapy for pump stoppage is surgical pump exchange. For patients unable to undergo surgery, a temporary stabilizing maneuver is to percutaneously occlude the outflow cannula to halt the backflow of blood through the valveless outflow cannula.

Stroke — Strokes remain a leading cause of long-term mortality in patients with LVADs. The incidence of stroke has not decreased with the transition from pulsatile to continuous flow devices. The incidence of ischemic and hemorrhagic stroke following LVAD placement has been reported to be 8 to 25 percent during the first several months following implantation [53,54]. Either type of stroke may occur in the immediate postoperative period as well as late after LVAD placement. For continuous flow LVADs, rates of ischemic stroke have ranged from 0.05 to 0.1 per patient-year, and rates of hemorrhagic stroke have ranged from 0.01 to 0.08 per patient-year [22]. In a study of 307 LVAD patients, 43 patients (24 of 167 HMI, 19 of 140 HMII patients) had a stroke (n = 35) or transient ischemic attack by a mean of 92 days postoperatively [54]. Multivariate analysis identified postoperative infection and prior history of stroke as the strongest predictors of a neurologic event. Strokes in LVAD patients tend to occur with greater frequency in the right hemisphere, which is suggestive of a cardioembolic rather than atherogenic source [55,56].

The HW device is associated with greater rates of stroke than seen with the HMII (or HM3) device, and was ultimately removed from the market [57]. An FDA Safety Communication noted that the preliminary report for a clinical trial comparing the HW device with the HMII for destination therapy included a 28.7 percent rate of stroke over two years for the HW device as compared with 12.1 percent for the HMII [23]. The ENDURANCE trial compared event rates at two years with HW and HMII devices in nontransplant-eligible patients: in the HW arm, 17.6 percent had an ischemic stroke and 14.9 percent had a hemorrhagic stroke compared with 8.1 percent ischemic stroke and 6 percent hemorrhagic stroke in the HMII arm [58].

There are a variety of mechanisms that can lead to an increased risk of thrombosis and subsequent neurologic events, including partial inflow cannula obstruction, deformation of blood pathway within the pump, twisting or kinking of the outflow graft, inadequate anticoagulation, and increased systemic inflammatory response as a result of infection. Control of blood pressure is one intervention that may be effective in preventing CVA as suggested by data in HW patients. A mean arterial blood pressure of >90 mmHg was associated with a greater stroke risk especially hemorrhagic strokes [59].

Evaluation of MCSD patients presenting with a new neurologic deficit includes assessment of current and recent INR, neurology consultation, head CT, and evaluation for pump thrombosis or malfunction [12]. (See 'Thrombosis' above.)

Anticoagulation is discontinued and reversed if hemorrhagic stroke is identified. (See "Overview of the evaluation of stroke" and "Reversal of anticoagulation in intracranial hemorrhage".)

Abdominal complications — Abdominal complications caused by VAD implantation were common with the bulkier pulsatile first-generation devices, particularly the HMI device, which was inserted into the abdomen with risk of subsequent gastrointestinal obstruction, fistula, and adhesions. However, these abdominal complications are rare with the axial flow pumps and with devices that are not implanted into the abdomen such as the HW device.

Ventricular arrhythmias — Ventricular arrhythmias can occur following LVAD implant. This is particularly true in patients with a prior history of ventricular arrhythmias. Generally, ventricular tachycardia is well tolerated given the circulatory support; however, persistent ventricular arrhythmias can predispose the patient to the development of right HF. If the arrhythmia is refractory to medical therapy, then catheter ablation may be required [60,61].

MEDICAL MANAGEMENT — Medical management of MCSD patients includes HF therapy and management of hypertension and other concurrent conditions.

Heart failure therapy — The components of HF therapy are similar to those used to treat systolic HF [12] and are discussed separately. (See "Overview of the management of heart failure with reduced ejection fraction in adults".)

Hypertension — For patients with nonpulsatile mechanical circulatory support devices (MCSDs), although the International Society for Heart and Lung Transplantation and European Association for Cardiothoracic Surgery recommend a mean blood pressure goal of ≤80 mmHg, we suggest a mean blood pressure goal of <90 mmHg [12,62,63]. For patients with pulsatile MCSDs, the blood pressure goal is a systolic blood pressure <130 mmHg and a diastolic blood pressure of <85 mmHg [12]. HF medications (angiotensin converting enzyme inhibitor, angiotensin II receptor blocker, beta blocker, hydralazine, nitrates) are the preferred agents for blood pressure management.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults".)

SUMMARY AND RECOMMENDATIONS

●Evaluation of pulse and blood pressure – Continuous flow left ventricular assist device (LVAD)-supported patients frequently have no palpable pulse and blood pressure may not be measurable by auscultation. Blood pressure is best estimated in these patients using a Doppler ultrasound probe and sphygmomanometer. (See 'Physical examination' above.)

●Indications for echocardiography – An echocardiogram is indicated in continuous flow LVAD-supported patients if there are unexplained symptoms of fatigue, device alarms, defibrillator discharges, dizziness, or increased right heart failure (HF). (See 'Echocardiography' above.)

●Device interrogation – Device interrogation includes review of alarm alerts, flow, pump power, pulsatility index (Pulse Index), and pump speed. (See 'Device interrogation' above.)

●Antithrombotic therapy – Patients supported by VADs are treated with systemic anticoagulation and antiplatelet agents to reduce the risk of thrombotic complications such as device thrombosis and embolic stroke. However, too early or too aggressive anticoagulation should be avoided to reduce the risk of bleeding complications. (See 'Antithrombotic therapy' above.)

●Complications – Complications following VAD implantation include bleeding, acute and chronic right HF, device thrombosis, infection, stroke, aortic regurgitation, ventricular arrhythmias, and hemolysis. (See 'Complications of VADS' above.)