Specific Critical Care Problems in Heart and Heart–Lung Transplant Recipients



Specific Critical Care Problems in Heart and Heart–Lung Transplant Recipients


Sara J. Shumway

Eias E. Jweied



The advent of thoracic organ transplantation has brought new hope to patients who were previously doomed by end-stage cardiac, pulmonary, or combined cardiopulmonary disease. The first heart transplant was performed on December 3, 1967. Fourteen years passed before the first successful heart–lung transplant was performed on March 9, 1981. Heart–lung transplantation established the potential for lung transplantation as a viable therapeutic option, and the first successful single-lung transplant was performed in 1983 [1].


Heart Transplantation

The United Network for Organ Sharing (UNOS) is a nonprofit organization that maintains the nation’s organ transplant waiting list. Patients awaiting cardiac transplants are listed according to severity of illness. Organs are then allocated to those individuals who are severely ill and have waited the longest. Just more than 2,200 heart transplants are performed annually in the United States. There has been a decrease in candidate waiting times, with the average waiting time for a status 1A heart candidate of 50 days and a status 2 candidate of 309 days [2]. A status 1 heart candidate includes those individuals with highest medical urgency. These are patients who have support either via a total artificial heart, ventricular assist device (VAD), intra-aortic balloon pump, or extracorporeal membrane oxygenation. It could also be an individual who has a mechanical assist device in place, either right or left support that is beginning to malfunction. It also includes individuals who are on continuous mechanical ventilation or on high-dose inotropic support and are unable to be weaned. Status 2 candidates are individuals who need a heart transplant but have not been defined as being in the most urgent status. They may be patients who are at home and taking heart-failure medications and are still active
and awaiting transplant but are not as critically ill as those individuals in the status 1 category. At any given time, UNOS has approximately 3,000 candidates listed for heart transplant, and most have been waiting for more than a year.

The number of heart transplants performed nationally depends on donor availability. In spite of this, the annual mortality rate on the waiting list has slowly declined during the last 10 years. In the middle to late 1990s, it was not uncommon to have anywhere between 700 and 800 people die from cardiac disease while awaiting a heart transplant. That number has been slowly decreasing to less than 400 each of the last 3 years [2]. This slow decrease is related to the evolution of left ventricular assist devices and their acceptance as a bridge to transplant.

Ninety percent of adult candidates listed for heart transplant have end-stage cardiac disease with some form of cardiomyopathy. Approximately 47% have idiopathic cardiomyopathy, and 35% have ischemic cardiomyopathy. The remaining 15% of heart transplant candidates have end-stage valvular disease, cardiomyopathy associated with congenital heart disease, or graft failure requiring retransplantation. Cardiac retransplantation represents approximately 4% of the adult heart transplant population annually [2,3].


Patient Selection

Many of the specific critical care problems seen in thoracic organ recipients can be reduced by careful patient selection. In well-compensated patients, a weeklong outpatient evaluation is performed. This applies to approximately 80% to 90% of patients seen at a cardiac transplant center. The other 10% to 20% are individuals who are desperately ill and undergo an urgent transplant evaluation.

The recipient assessment consists of a general evaluation, an assessment of the functional and hemodynamic status, and a psychosocial evaluation. All parts are equally crucial. One of the first assessments is an oxygen-consumption treadmill test. For those patients who are capable of performing this test, there are excellent data that demonstrate that a peak oxygen consumption of less than 12 mL per kg per minute is associated with a very poor 1-year survival rate without transplant. Individuals with a peak oxygen consumption of less than 15 mL per kg per minute should be considered for listing [4,5]. The assessment then proceeds with a general evaluation. The patient’s medical history is examined to try to determine the cause of the patient’s heart disease. General laboratory tests are performed, including a creatinine clearance. Individuals who have a creatinine clearance of less than 50 mL per minute do have a significant increase in the need for postcardiac transplant dialysis and a decrease in survival rate. Individuals with severely abnormal creatinine clearance would be excluded from heart transplant or considered for heart and kidney transplantation. Individuals with diabetes need further end-organ evaluation prior to listing to understand the full scope of their risk.

Nutritional status is also crucial. Those individuals with a body mass index less than 20 kg per m2 or greater than 35 kg per m2 would be asked to either gain or lose weight, respectively. Again, individuals at the extremes of the body mass index have an associated increase in postoperative mortality [6,7].

The hemodynamic evaluation consists of an echocardiogram to evaluate function and anatomy, and a cardiac catheterization. The cardiac catheterization includes evaluation of heart function by a right heart catheterization as well as a coronary angiogram. In this assessment, the patient’s coronary anatomy is examined for potential intervention, and any abnormalities in the filling pressures, pulmonary capillary occlusion pressure, or pulmonary vascular resistance are identified.

Patients with heart failure and secondary pulmonary hypertension are a group who are of special interest. Pulmonary arterial and capillary wedge pressures are measured to determine the degree to which a patient has secondary pulmonary hypertension and whether or not it is reversible. The patient’s hemodynamics should be optimized in the catheterization laboratory in an attempt to decrease the pulmonary arterial pressures to normal levels, and 100% oxygen, nitric oxide, and other pulmonary vasodilators can be used to test for reactivity in the pulmonary bed. The absolute exclusion criteria for heart transplantation are a pulmonary vascular resistance greater than 4 Wood units (WU) and, more importantly, a transpulmonary gradient greater than 15 mm Hg. Individuals with values outside these values would then be listed for heart–lung transplant, or be given a trial of pulmonary vasodilators.

The patient’s ABO blood type and panel-reactive antibody (PRA) level is determined to quantitate the patient’s preexisting antibodies and sensitization to the general population. If class II (locus D) is greater than 20%, it is recommended that a preoperative cross-match be performed. The patient’s HLA typing is also done at that time, and if the PRAs are significantly elevated, the laboratory should be able to identify the particular human leukocyte antigen to which the individual is reacting. Sensitization can occur in many situations. It may occur because of pregnancy, between sexual partners, from prior transplantation, or with transfusions often associated with the placement of a ventricular assist device. Individuals who carry a high PRA level have been treated in the past with plasmapheresis, intravenous immunoglobulin, cyclophosphamide, and mycophenolate mofetil (MMF). There have been inconclusive results with each of these.

The psychosocial evaluation should be centered on evaluating not only the transplant recipient but also the family support for the patient. This needs to be performed by a social worker and, when indicated, other mental health professionals who have a keen understanding of the demands made on a postoperative cardiac transplant patient. Patients need to be medically compliant, have adequate neurocognitive function for the postoperative regimen, and adequate social support.

Once the evaluation has been completed, the patient is evaluated for any relative or absolute contraindication for heart transplant. Those relative contraindications include age greater than 70 years, previous chronic substance abuse, limited social support, limited adaptive ability, mild renal dysfunction, active peptic ulcer disease, cachexia, obesity, and cigarette smoking. It should be noted that to receive a heart transplant, individuals who smoke are required to go through a smoking-cessation program, and many transplant programs require them to sign a contract stating that they will not resume smoking prior to or after the transplant. They also are evaluated for chemical evidence of smoking during their waiting time [8].

Absolute contraindications to cardiac transplantation include ongoing substance abuse, refractory psychiatric conditions, suicidal behavior, severe personality disorder, issues with ongoing medical noncompliance, inadequate neurocognitive ability, irreversible hepatic or renal dysfunction, severe peripheral or cerebral vascular disease, systemic disease that limits rehabilitation, insulin-dependent diabetes with severe end-organ damage, and evidence of severe, fixed, secondary pulmonary hypertension [8,9,10].


Implantable Cardiac Assist Devices

The proliferation and success of ventricular assist devices probably represent the greatest advance in the treatment of end-stage heart failure and the field of heart transplantation of the past 10 years (Table 183.1). With an assist device implanted, patients who would otherwise not survive long enough to
receive a heart transplant are now living independently at home with reasonably good quality of life until a suitable organ becomes available. Today, at high-volume heart transplant centers, many if not most patients arriving for heart transplantation have an assist device already in place and it can be expected that in the coming years most if not all heart transplant recipients will have had one of these devices implanted by the time they receive an organ.








Table 183.1 Advances of Ventricular Assist Devices in Heart Failure Treatment


















Topic Finding Reference
Destination therapy trial with pulsatile pumps Improved survival at one year with mechanical assist device vs. medical management for Class III and IV heart failure [11]
Bridge to transplant trial with continuous flow pumps HeartMate II provides effective support to transplant for at least 6 months with 75% survival [12]
Improved survival with continuous flow pumps Effective support, improved functional status and quality of life with 72% survival at 18 mo [48,49,50]

From their increased use, a corpus of terminology has evolved to categorize and describe the devices themselves, their use, and technical aspects of their function and performance. Most devices are designed to assist the left ventricle and hence are called left ventricular assist devices (LVADs). However, some models are made to be implanted in either ventricle and when implanted on the right side are referred to as a right ventricular assist devices (RVAD). When both ventricles are mechanically assisted, each with its own pump, the whole system together is referred to as a biventricular assist device, or BIVAD.

There are two broad categories of devices in use based on pump mechanism: pulsatile devices that employ some type of pneumatic pump, and continuous, or axial, flow devices that involve a spinning propeller. The cycles of the pulsatile device are measured in beats per minute (bpm) and that of the continuous flow pumps in revolutions per minute (rpm). Each device has an inflow cannula through which the patient’s blood is drawn from the heart and into the pump and an outflow cannula that directs the blood back into the patients’ circulation.

Further, for both pulsatile pumps and continuous flow pumps, there are two more classifications that can be described on the basis of the location of the pump when implanted: intracorporeal wherein the entire pump is implanted inside the body with the exception of the drive-line that powers the device and passes through an exit site on the abdomen; the other is paracorporeal, or extracorporeal, wherein the pump sits outside the body and the inflow and outflow cannulae enter and exit the skin on the upper abdomen just below the costal margin.

Most LVADs usually involve an inflow cannula placed in the apex of left ventricle and the outflow cannula in the ascending aorta. The only permanent RVAD approved for use in the United States is the Thoratec® Paracorporeal Ventricular Assist Device and its inflow cannula is placed in the right ventricular free wall and the outflow cannula is anastomosed to the pulmonary artery. The Levitronix® CentriMag (now owned by Thoratec®) is approved for temporary right ventricular assistance up to 30 days and its inflow cannula may be placed in either the right atrium or the right ventricle.

Lastly, there is a categorization of devices based upon the intended therapeutic goal for each particular patient. Bridge to transplant (BTT) indicates that the patient is or will become a heart transplant candidate and the device is intended to improve survival and other physiologic parameters until an organ is available. Destination therapy (DT) indicates that the patient is not a transplant candidate but the device is implanted to improve survival and quality of life for the remainder of the patient’s life. Bridge to recovery refers to the patient who is expected to recover from heart failure and the device is used to sustain life until the time when it can be weaned off and explanted. Bridge to decision (BTD) refers to those patients for whom survival is not certain and a temporary assist device, such as the AbioMed BVS5000™ or the Levitronix® CentriMag, is used in the critical care setting to prolong life until it can be determined whether the patient ought to be implanted with a long-term device as those used in BTT or DT patients or be disconnected from the BTD device and allowed to expire.

The superior efficacy of VADs over optimal medical management in improving survival in end-stage, New York Heart Association Class 3 or 4 heart failure patients was proven in the REMATCH trial: patients implanted with the Thoratec® HeartMate VE had a 52% survival at one year compared to 25% in the medically managed group [11]. Subsequently the Food and Drug Administration (FDA) approved the HeartMate XVE for destination therapy. The Thoratec® HeartMate II continuous flow pump demonstrated efficacy in bridge to transplantation with 75% survival at 6 months postimplantation and 68% survival at 1 year [12]. It received approval by the FDA in April 2008 for bridge to transplantation and was subsequently approved for destination therapy in January 2010. Smaller devices such as the Jarvik 2000 Flowmaker™ and the HeartWare™ VAD are currently under investigation in the United States with more than two dozens other devices presently in development (Fig. 183.1).

Knowing how these devices work and how these patients are managed will be an important part of the pretransplantation care of the recipient, and indeed any critically ill patient who is admitted with one of these devices. Almost all of these patients will arrive anticoagulated on warfarin. It will be important not to begin administration of plasma and cryoprecipitate until the plan to proceed with the transplant is certain. Administration of blood products without completing the transplant will only sensitize the recipient and increase the PRAs for any subsequent transplant offers [13]. The postoperative course is often complicated by bleeding. Drains for the VAD pocket are necessary and pericardial effusions are more common.

Several studies have examined posttransplant survival and recent studies have shown that recipients of ventricular assist devices have had equal or better posttransplant outcomes [14,15]. One exception is the patient who had VAD-related sepsis prior to transplantation as these patients had a trend to slightly poorer posttransplant survival than those patients who did not have an infection [16].


Donor Criteria

The donor evaluation begins with the pronouncement of brain death. The local organ procurement agency will obtain consent
for donation from the family and proceed with the donor evaluation and support. The donor evaluation consists of taking a general history of any illnesses or risk factors such as heart disease, hypertension, diabetes, or cigarette smoking. Specifics are gathered surrounding the time and mode of death to determine whether there is any potential cardiac injury, down time, cardiopulmonary resuscitation, or cardioversion. The organ-procurement professionals will proceed with a hemodynamic evaluation of the patient. This consists of at least measuring central venous pressures and, potentially, full hemodynamic profiles if pulmonary artery catheter measurement capability exists at the donor hospital. Once the donor is stabilized hemodynamically, further studies are performed. The initial stabilization phase should include endocrine support with the administration of levothyroxine and corticosteroids, reduction of inotropic support if it is appropriate, and, potentially, diuresis or transfusion if needed. A surface echocardiogram is then performed to make sure the heart is structurally normal and that function is normal. A 12-lead electrocardiogram is also obtained. It is not uncommon to find subtle ST changes in individuals who are brain-dead. It is generally accepted that a cardiac catheterization will be necessary in male donors more than 40 years old and female donors more than 45 years old, but catheterization should also be performed in younger donors if the donor has a significant history of hypertension, cigarette smoking, diabetes, or alcohol abuse. Cardiac enzymes need to be carefully evaluated and correlated to any severe hemodynamic instability, the use of cardiopulmonary resuscitation, as well as the time of herniation [17].






Figure 183.1. Continuous flow ventricular assist devices. A: HeartWare ventricular assist device. [Reprinted with permission from HeartWare™.] B: HeartMate II ventricular assist device. [Reprinted with permission from Thoratec®.]

A number of studies have demonstrated correlations between elevations of troponin and early graft failure [18,19]. In one study, a cardiac troponin I value greater than 1.6 μg per L was a predictor of early graft failure, with a sensitivity of 73% and a specificity of 94% [18]. These data should be analyzed closely with the patient’s hemodynamic function and echocardiographic findings.

A transplant center may request that a second echocardiogram be performed if the first echocardiogram was performed shortly after herniation. Catecholamine-induced left ventricular dysfunction can improve significantly in a short period of time and not preclude excellent short- and long-term outcomes. One must also take into consideration the ischemic time that will be incurred with procurement and travel time. The majority of transplant centers are willing to accept an ischemic time up to 4 hours for adult donors but no more than 6.

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Sep 5, 2016 | Posted by in CRITICAL CARE | Comments Off on Specific Critical Care Problems in Heart and Heart–Lung Transplant Recipients
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