to implantation of an MCS device. Severe aortic stenosis, however, should be corrected, preferably with

a bioprosthetic valve. This is thought to facilitate future weaning and optimize native heart function if

the indication for device implantation is for myocardial recovery. The presence of greater than mild

aortic insufficiency can have a significant impact on the effectiveness of MCS therapy as it leads to LV

distention and a decrease in subendocardial blood flow. In cases where MCS support is established via

LV apical cannulation (more commonly with implantable MCS devices used for BTT or DT), reductions

in LV end-diastolic pressure elicited by MCS increase the pressure gradient across the aortic valve and

increase the degree of aortic insufficiency, decreasing net forward flow and compromising end-organ

perfusion. The presence of aortic insufficiency can be confirmed by perioperative echocardiography and

addressed by either AV replacement with a bioprosthesis or repair.31 Patients with a mechanical valve

prosthesis in the aortic valve position should have the mechanical valve replaced with a bioprosthetic

valve prior to institution of LV assistance. During unloading of the LV by an LVAD, the aortic valve may

not open and the mechanical valve may be prone to thrombosis. Development of aortic insufficiency

after LVAD implantation may be addressed at a later date with aortic valve replacement, via either open

surgical or transcatheter aortic valve replacement.32,33

Patients with significant mitral stenosis at the time of initiation of device support may require

correction of the valvular problem before implantation of a device depending on device selection and

site of cannulation. In the setting of significant mitral stenosis, LV filling is impaired, and VADs

requiring apical ventriculotomy for ventricular drainage may experience limitations in device filling.

This problem can be circumvented either by choosing a device that can utilize left atrial cannulation or

by correcting the underlying valvular pathology (mitral valve repair or replacement with a

bioprosthetic valve). Mitral regurgitation likely does not have an impact on the filling of a VAD. In

situations where weaning from MCS may be feasible, correction of the mitral pathology (stenosis or

regurgitation) is necessary to optimize ventricular function.

Adequate RV function is extremely important to maintain LVAD flow in the early postoperative

period. Significant degrees of tricuspid regurgitation (present preoperatively or resulting from septal

shift following implantation of an LVAD) can impair the flow of blood from the RV, particularly in

situations of high pulmonary vascular resistance. Tricuspid regurgitation and RV dilatation contribute to

elevated central venous pressure, hepatic congestion, and renal dysfunction.20–25 It is generally

recommended that moderate or more degrees of tricuspid regurgitation be repaired at the time of LVAD

implant to improve RV performance.

Coronary Artery Disease

Patients with significant obstructive coronary artery disease or patients with postcardiotomy shock

following failed coronary bypass operations may experience angina during MCS. Generally, coronary

artery disease does not have adverse hemodynamic consequences during the period of MCS. However,

the presence of obstructive coronary disease with ongoing ischemia may limit the degree of myocardial

recovery and impact the ability to wean from temporary MCS. The presence of coronary disease may

contribute to ongoing myocardial ischemia and increase the risk of ventricular arrhythmias for patients

supported with temporary or durable MCS.

Perioperative ischemia of the RV may be of hemodynamic significance during initiation of LVAD

support. In patients who have had coronary bypass surgery and are candidates for MCS, patent bypass

grafts, particularly to the right coronary artery or left anterior descending coronary artery should be

preserved to reduce the risk of perioperative RV failure and arrhythmias. In highly selected situations, it

may be important to perform a coronary artery bypass to the right coronary artery or left anterior

descending coronary artery systems to optimize RV or septal function in the perioperative period.

Routine bypass grafting of the right coronary artery is not warranted.

Arrhythmias

Atrial and ventricular arrhythmias are common in patients with cardiogenic shock and underlying

cardiomyopathies. These rhythm disturbances generally persist in the immediate postoperative period

and subsequently resolve with time as the hemodynamic condition of the patient improves and inotrope

therapy is weaned. Recent experience has revealed that the hemodynamic consequences of ventricular

arrhythmias in the late postoperative period are generally not life-threatening. In the absence of

pulmonary hypertension and elevated pulmonary vascular resistance, patients may maintain lifesustaining degrees of LVAD flows during ventricular fibrillation via Fontan-like (systemic vein to

pulmonary artery) circulation.34 In the early perioperative period, some patients with refractory

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ventricular arrhythmias may require biventricular support until the pulmonary vasculature resistance

drops and a Fontan circulation is tolerated. In situations where weaning from MCS is feasible or

planned, elimination of the ventricular arrhythmias with antiarrhythmic therapy is essential.

The majority of patients undergoing implantation of a long-term durable VAD for either BTT or DT

indications have an implantable cardiac defibrillator (ICD) in place for either primary or secondary

prevention of ventricular arrhythmias as part of their care for advanced heart failure. Generally, these

device therapies are continued following VAD implantation. Currently, for those patients who do not

have an ICD at the time of VAD implant, International Society for Heart and Lung Transplantation

(ISHLT) guidelines recommend routine evaluation for ICD therapy.35 The survival benefit of ICD

therapy in the setting of VAD support is, however, controversial with some studies identifying benefit

and other studies finding no additional survival benefit over that obtained with VAD implantation

alone.36

Intracardiac Shunts

Intracardiac shunts (atrial septal defects or patent foramen ovale) identified by transesophageal

echocardiography prior to surgery should be closed at the time of implantation of a VAD to prevent

right to left shunting.37 As LV assistance is initiated, left atrial pressure can be reduced compared with

right atrial pressures causing shunting of deoxygenated blood from the right atrium into the left

resulting in systemic hypoxemia.

PATIENT OUTCOMES AND MAJOR ADVERSE EVENTS FOLLOWING

INITIATION OF MCS

7 Survival and occurrence of significant adverse events following initiation of MCS therapy are

dependent on the clinical presentation, indication for MCS therapy, and type of device implanted.

Bleeding, stroke and thromboembolism, infection, and RV failure are the most frequent complications

that occur in the early postoperative period following initiation of MCS and are more commonly

encountered when devices are implanted in an emergency situation. Major adverse events most

common in the late postoperative period include bleeding and thromboembolic events (e.g., stroke)

with or without associated device failure.

Bleeding

Bleeding is a frequent, early complication in patients supported by MCS and may require reoperation in

the early postoperative period. Risk factors for bleeding include preoperative hepatic congestion and

failure, poor preoperative nutritional status, prolonged CPB times, extensive surgical dissection,

reoperative surgery, multiple cannulation sites, decreased platelet function, and induction of fibrinolysis

as a result of contact of blood with biomaterial surfaces during CPB and with MCS devices. Even though

meticulous surgical technique is of outmost importance, it is important to note that numerous MCS

centers employ various surgical techniques with equivalent results.

Nonsurgical bleeding is one of the most common adverse events within the first 30 days after durable

VAD implantation.38–42 Across studies, the most commonly reported sources of bleeding are epistaxis, GI

tract bleeding, bleeding of the mediastinum and thorax, and intracranial hemorrhage.38–43 However, the

location of bleeding may vary depending on time from operation, with thoracic or mediastinal bleeding

having higher, but diminishing, risk in the early postoperative period, with a later risk of GI tract

bleeding. Recent data have demonstrated that support with long-term durable MCS is associated with

development of acquired von Willebrand’s disease caused by high shear stresses within continuous flow

rotary pumps that result in degradation of high–molecular-weight von Willebrand multimers and

activation of the enzyme ADAMTS13, a zinc-containing metalloprotease enzyme that cleaves von

Willebrand factor.41–43 Acquired von Willebrand disease has been associated with a high incidence of

late bleeding in patients supported with long-term durable VADs manifest at mucosal sites including

gastrointestinal bleeding and epistaxis and appears to accentuate previous subclinical arteriovenous

malformations, commonly found in patients on MCS.44

RV Failure

RV failure occurs in approximately 3% to 30% of patients supported by LVAD support alone. The large

variation in occurrence of RV failure is dependent on a number of important patient factors including

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severity of illness and timing of intervention. The etiology of RV failure is multifactorial and includes

pathologies within the pulmonary vascular bed and/or RV. Factors contributing to RV failure include

impaired RV function as a result of intraoperative air embolism, myocardial stunning due to poor

intraoperative myocardial protection, ischemia secondary to coronary artery disease, arrhythmias,

volume loading, and alteration of RV septal geometry induced by LV unloading. Several studies have

demonstrated that factors such as elevated central venous pressure, reduced RV stroke work index, low

preoperative pulmonary artery pressures, increased transpulmonary gradient greater than 16 mm Hg,

acute decrease in pulmonary artery pressures equal to or greater than 10 mm Hg at the onset of LVAD

support, degree of preoperative pulmonary edema, increased need for perioperative transfusions,

increasing degree of renal and hepatic dysfunction, female gender, nonischemic etiology, and

preoperative temporary MCS support, all increase the need for RV MCS following LVAD

implantation.8–13,20–25 Among the 484 patients enrolled in the HeartMate II LVAD bridge-totransplantation clinical trial, 6% required mechanical right-ventricular support while 14% required

prolonged inotrope therapy. Multivariate data analysis revealed that a central venous

pressure/pulmonary capillary wedge pressure ratio greater than 0.63, need for preoperative ventilator

support, and blood urea nitrogen level higher than 39 mg/dL were independent predictors of right-sided

heart failure after LVAD implantation.20 Acute unloading of the LV by MCS may cause the septum to

shift leftward, increasing RV volume loading and reducing its function.23–25 The negative consequences

of this phenomenon may be offset by the reduction in pulmonary artery pressures and RV afterload

caused by device-mediated LV decompression.23–25 Hemodynamic stability can be attained with isolated

mechanical LV support in the overwhelming majority of patients, even in those patients with substantial

RV dysfunction, if there is effective replacement of left-sided heart function and aggressive treatment of

pulmonary hypertension. More recently, the improved perioperative management of elevated

pulmonary vascular resistance including the use of inhaled nitric oxide, a specific, potent pulmonary

vasodilator, in combination with milrinone, isoproterenol, or dobutamine has significantly reduced the

need for placement of an RVAD.45 In patients with marked elevation of central venous pressure,

multiorgan failure, and severe RV dysfunction with low pulmonary artery pressures, early biventricular

support may be indicated.45 Posttransplantation survival among the patient requiring prolonged RV

support (mechanical or otherwise) tends to be lower when compared with those with preserved RV

function following an LVAD implantation.20

Intracranial Bleeding and Thromboembolism

Intracranial hemorrhage is one of the most feared complications of MCS. The reported rates of

hemorrhagic stroke are fortunately low and range from 0.01 to 0.08 events per patient-year.44

The occurrence of thromboembolic events following MCS is variable and depends on a number of

factors including the type of device, duration of support, location and number of cannulation sites, and

the presence of prosthetic valves within the heart. Approximately 10% of patients receiving MCS with

implantable devices will experience a thromboembolic event or stroke.38,39,46 This rate is in the range of

20% for patients on short-term extracorporeal MCS devices.1 Improvement in the rate of

thromboembolic events has come from more aggressive antiplatelet therapy in conjunction with

warfarin, improved device design, and more frequent use of LV apical as compared with left atrial

cannulation. In patients supported only for short durations, anticoagulation is usually achieved with

heparin and antiplatelet therapy. Longer-term support usually requires transition to warfarin and

antiplatelet therapy.

Infection

Infections can be device-related (i.e., device endocarditis, percutaneous lead or cannula site infection,

pocket infection [infection external to an implanted device]) or nondevice-related (i.e., pneumonia and

urinary tract infection). The incidence of early nosocomial device-related infections in patients

undergoing MCS is approximately 30% in many series and is related to the acuity of illness in this

population of patients.38,39,46–51 Patients with persistent or recurrent sepsis, and those patients with

device-related infections, tend to have a higher mortality rate than patients without these

complications.51 In patients on long-term MCS, infection remains an important obstacle to successful

outcome.51 Most of these late infections begin in the percutaneous driveline tract and pocket of the

device. However, clinical experience has revealed that VAD infection rates can be minimized with

attention to infection control guidelines, optimal implantation techniques, meticulous wound care, and

the utilization of new continuous-flow rotary pump technology.51

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Risk factors for development of infection present before device insertion include preoperative

infection at remote sites (not in the area of implantation), malnutrition, prolonged hospitalization,

immobilization, broad-spectrum antibiotic therapy, immunosuppressive medications, mechanical

ventilation, and the presence of central venous catheters. The percutaneous lead of the device can be a

port of entry for bacterial and fungal pathogens. Intracorporeal device infections can occur within the

pumps themselves and on their outer surfaces, which are generally caused by biofilm-forming bacteria

and fungi. Device-related infections can sometimes be successfully treated with antibiotic suppression

and device exchange or removal. Infections involving the preperitoneal pocket (subfascial space created

for device placement) surrounding implantable VADs require more aggressive treatment, including open

drainage, debridement, omental translocation, and rerouting of the percutaneous lead through a fresh

exit site. However, patients who are device-dependent and awaiting transplantation generally cannot

tolerate device removal as a therapeutic option to eradicate the infection. Antibiotic suppression and

transplantation remain the only chance for cure of device-related infections in these instances. These

infections do not generally preclude heart transplantation. However, transplant survival is adversely

influenced by the presence of MCS infections at the time of heart transplant and MCS explant.

Device Malfunction and Thrombosis

As with any mechanical device, malfunction is an anticipated occurrence. The types and severity of

device malfunctions vary with each of the devices. Many devices have built-in backup systems that, in

the event of catastrophic device failure, provide support to the patient. In some instances, patients

supported by a VAD have enough residual LV function remaining to help sustain them until corrective

measures can be taken in the event of complete device failure. New technology incorporating

continuous-flow rotary pump design present new challenges to device malfunction. These devices do not

contain valves to direct the flow of blood, and stoppage of the pump is associated with significant

regurgitation of blood through the device resulting in significant LV distension. This phenomenon is

similar to the development of acute aortic insufficiency. Fortunately, the reported frequency of this

event is low.32,33 Device malfunctions in TAHs are more problematic as there is no native heart to

provide hemodynamic support in the event of a total device failure. Stringent quality control measures

in fabrication and testing and very low mechanical failure rates are, therefore, even more essential with

TAHs.

Pump thrombosis is potentially a catastrophic complication of VAD therapy. The variability in clinical

presentation makes it a challenging diagnosis. It occurs both early and late after VAD implantation and

may manifest itself with increased pump power, decreased device flow with heart failure, and hemolysis

with hemoglobinuria or with embolic event (peripheral or neurologic). With echocardiography

examination, worsening mitral regurgitation, left ventricular distention or persistent opening of the

aortic valve, or inability to decompress the LV with increasing degrees of LVAD pump speeds may aid in

confirming the diagnosis. Serum lactate dehydrogenase level seems to have established itself as the

primary biochemical marker of hemolysis in this clinical context. The rates of device thrombosis

initially reported at 2% to 4% in the pivotal Heartmate II trials may underrepresent the true incidence

of this complication in durable VADs.38,39,49 A recent report looking at incidence of pump thrombosis at

three high-volume centers suggests an abrupt increase in the recent years and occurring at the rates of

4.7%, 7.5%, and 12.3% at 6, 12, and 24 months, respectively.52–54 Clinically suspected thrombosis can

be managed medically by intravenous anticoagulation, antiplatelet agents, or thrombolytics in some

cases. Surgical treatment by pump explantation with either pump replacement or urgent heart

transplantation is generally required in most circumstances.

Interagency Registry for Mechanically Assisted Circulatory Support

8 The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database,

sponsored by the United States National Heart, Lung and Blood Institute (NHLBI), is a registry for

patients who receive implantable or “durable” MCS devices that are approved by the FDA.13 The

INTERMACS registry represents one of the largest available data repositories for the study of durable or

long-term MCS device outcomes. The most recent published data analysis of MCS outcomes for VAD

therapy reviews the nearly 6 years of data entry into the registry with more than 10,000 patients.13 It

includes data on a variety of pulsatile and continuous flow rotary pumps and TAHs. Survival with LVAD

support alone at 1 and 2 years continues to be 80% and 70%, respectively, and is significantly worse for

those patients requiring BiVAD or TAH support13 (Figs. 84-5 to 84-7). MCS as DT strategy continues to

represent the majority of implants and the proportion of patients treated in this fashion has increased

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