Heart transplantation evaluation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gaurang Vaidya, M.D.[2]

Overview

An exhaustive evaluation of patients intended for heart transplant listing is indicated in all cases. The evaluation includes demographic assessment, blood group typing, echocardiography, cardiopulmonary exercise stress test heart catheterization, and noncardiac assessment.

Evaluation of patients for heart transplantation

An exhaustive evaluation of patients intended for heart transplant listing is indicated in all cases.

Evaluation of patients for heart transplantation
Initial demographic assessment:	This includes consideration for the patient’s age, gender, and body-mass index. Patients up to 70 years of age are eligible for a heart transplants. However, on some occasions and at some centers, appropriate patients >70 years of age may be considered. Body mass index (BMI) ≤ 35 kg/m2 is recommended prior to listing(11). Extremes of BMI (BMI >35 kg/m2 or < 18 kg/m2) are both associated with adverse post-transplant outcomes.
Blood group	Knowledge of the patient’s blood type is paramount to reduce incompatible transplants. Though ABO-incompatible heart transplant has been described in infants due to relative immaturity of their immune system (12), if done in adults it can result in hyperacute rejection. Notably, blood group O patients have the longest wait time for transplant as they can only accept group O donors (13). Blood groups A and B can accept their own group as well as group O donors. Group AB has the least waiting time as they can theoretically accept any blood group donor (13). Discussion of this with the patients before-hand can help manage expectations and risk-stratify them accordingly. A case can also be made to consider mechanical circulatory support early in blood group O patients anticipating longer wait times (13).
Cardiac Assessment
Echocardiography	Echocardiography is the ultrasound assessment of the heart function, valve function, restrictive diastolic changes and structural measurements. It can also help estimate right ventricular pressure, delineate the anatomy of congenital heart disease and even evaluate myocardial viability through stress modalities. Echocardiography is an important requirement for all patients (adult and pediatric) undergoing heart transplant evaluation.
Cardiopulmonary exercise stress test (CPX):	CPX is a stress test performed in patients able to exercise on a treadmill or a stationary bicycle. During the test, the patient wears a non-rebreathing mask while exercising and the exchange of oxygen and carbon dioxide is measured. The speed or the work-effort on the treadmill or bicycle is increased gradually. The patient continues to exercise until fatigue sets in and the patient have to stop. The peak oxygen consumption (peak Vo2) is measured at this time point. The test is considered maximal if the anaerobic threshold is reached. This is the point when the body switches from predominantly aerobic to anaerobic metabolism and is marked by a sudden surge in the carbon dioxide being exhaled compared to oxygen consumption. Respiratory exchange ratio (RER) is the ratio of carbon dioxide output to oxygen uptake (Vco2/Vo2) and an RER ratio >1.05 is considered a maximal test. A patient with poor heart function will reach the anaerobic threshold early and have low peak Vo2. On the other hand, patients who are physically deconditioned or put in a poor effort during exercise will not reach the anaerobic threshold during the CPX test. The test will then be considered non-diagnostic. If the anaerobic threshold is reached and the peak Vo2 value is < 14 ml/kg/min in the absence of beta-blocker or a value of < 12 ml/kg/min in the presence of a beta-blocker, then such a patient is estimated to have a survival of < 80% at 1 year. This could be considered criteria for heart transplantation(11). In patients unable to reach anaerobic threshold, the slope of minute ventilation (VE) and Vco2 can be used for prognostication. This ratio estimates the amount of ventilation needed to exhale 1 unit of carbon dioxide. A high value (>35) is indicative of slow delivery of carbon dioxide to the lungs and hence poor right ventricular hemodynamics. This again could be considered a criterion for listing(11). There are other CPX parameters that have also been proposed for prognostication, however, peak Vo2 and the VE/VCO2 slope are the ones used predominantly. It is important to keep in mind that the results of the test cannot be the sole reason for listing.
Heart catheterization (HC)	Right heart catheterization RHC (Right heart catheterization) is an invasive test involving guiding a pressure measurement catheter through a venous access site (jugular, femoral etc.) into the right ventricle and then the pulmonary artery. The test aims to measure the pressures in the right ventricle, pulmonary artery, and capillary wedge pressure which is the surrogate for the left ventricular end-diastolic pressure. The test can also measure cardiac output in liters/minute, vascular resistance in the pulmonary and systemic circuits, and other parameters. The procedure is ideally done while the patient is euvolemic or maximally fluid optimized. RHC is vital in the assessment of the patient’s baseline cardiac output, fluid status, and pressure in all chambers of the heart. This data can help optimize the hemodynamics and also estimate the severity of heart failure and hence the urgency of listing. Left heart catheterization or the non-invasive myocardial assessment In certain patients with newly diagnosed heart failure or with previously known coronary artery disease, a coronary artery angiography or non-invasive viability testing may be indicated to exclude underlying coronary artery disease which could be amenable to further invasive treatments. Heart transplant listing should ideally only be pursued after all potential invasive or surgical options have been exhausted.
Non- Cardiac Assessment
A comprehensive evaluation of all non-cardiac organ function is important to exclude life-threatening disease elsewhere independent of the incident heart failure. This is most often the most time-consuming step, but an exhaustive evaluation is paramount to a successful post-transplant outcome. A multidisciplinary team approach is essential to interpret the data and to provide expert consultation on the prognosis.
Serum creatinine	Serum creatinine is often used to calculate the estimated glomerular filtration rate (eGFR). An eGFR < 30 ml/min/1.73 m2 is an absolute contraindication to heart transplant alone (11). Similarly, an elevation of serum transaminases, bilirubin or prothrombin time should prompt further evaluation for cirrhosis. Patients >50 years of age or patients at risk should undergo appropriate screening for peripheral vascular disease. Females >50 years of age or with risk factors (steroid use or post-menopausal) are recommended to undergo a bone density assessment for osteoporosis as this may interfere with post-transplant rehabilitation and mobility (14).
Diabetes	Diabetes is common among heart failure patients (15) and is sometimes uncovered for the first time during a patient’s initial evaluation for heart failure. Therefore, hemoglobin A1c should be obtained in all patients. Poorly controlled diabetes with hemoglobin A1c >7.5%, especially with evidence of end-organ involvement (excluding non-proliferative retinopathy) is indicative of poor prognosis independent of heart failure. Such patients are also at risk of poor outcomes post-transplant due to recurrent infections, coronary artery disease in the graft, or recurrent heart failure (16). Poorly controlled diabetes is, thus, considered a relative contraindication to listing(11).
Antibodies	Antibodies to human leukocyte antigens (HLA): HLA is antigens present on the surface of the majority of the cells in the body. These antigens are used by the body’s immune cells to identify them as ‘belonging to the body’. They function like ‘identity cards’ carried by all the nucleated cells in the body to prevent the immune cells from attacking them. The immune cells identify foreign cells when they encounter non-self HLA antigens on the foreign cells. The immune system then mounts an attack through direct cellular injury or antibody-mediated injury, eventually killing these foreign cells. This is one of the ways the body ‘rejects’ a donor organ- by identifying the organ as non-self by the recipient’s immune system. Most of the antibodies against non-self HLA antigens are formed after exposure to the donor organ. This process of identifying non-self HLA and mounting an attack can take some time, usually days. However, some patients have pre-formed antibodies due to prior exposure to blood transfusions, another organ transplant, pregnancy, previous mechanical devices, etc. These preformed antibodies can mount an attack almost immediately after the donor organ is transplanted resulting in a hyper-acute rejection, which can be fatal. Identification of such pre-formed antibodies is thus important prior to the transplant, in order to avoid a donor who has that particular HLA to which the patient is sensitized to. In some cases, it is possible to reduce the pre-formed antibodies through certain desensitization protocols involving anti-cancer and other medications/procedures directed against immune cells and antibodies (17).
Cancer screening:	As discussed above, performing age and gender-appropriate cancer screening is important to exclude non-cardiac life-threatening disease prior to heart transplant. This is especially important as the immunosuppressant medications used after the transplant increase the risk of developing cancer or worsening pre-existing cancer (18). So much so that, cancer is one of the predominant causes of death post-transplant (18). Prior history of cancer usually necessitate consultation with an oncological expert to ascertain prognosis in terms of survival, relapse risk, and response to chemotherapy.
Substance abuse screening:	Tobacco smoking is associated with early graft failure, premature coronary allograft vasculopathy (CAV) and overall poor outcomes post-transplant(19,20). All patients should be screened for alcohol, tobacco, or illicit drug use history. Abstinence for 6 months may be necessary to consider for listing based on the individual institution policy.
Social, financial, and psychiatric screening:	All patients should be informed about the financial impact of heart transplantation. Apart from the medication and surgical costs, this also includes the inability to go back to work immediately, the need for translocation closer to the transplanting hospital, transportation costs, etc. A stable financial condition is desirable for optimal outcomes post-transplant (21). Psychosocial assessment should include an evaluation of a patient’s ability to comprehend and comply with medical instructions and exhibit strong caregiver support to help with the post-transplant care. The presence of active psychiatric illness that could impact medication compliance should be taken into consideration.