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Current Listing System

  • Deirdre M. Mooney
  • Marwa SabeEmail author
Living reference work entry
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Part of the Organ and Tissue Transplantation book series (OTT)

Abstract

The United Network of Organ Sharing (UNOS) is the Organ Procurement and Transplantation Network (OPTN) that oversees heart transplantation in the United States. In 2016, a 10-year update to the 2006 International Listing Criteria for Heart Transplantation was published by the International Society for Heart and Lung Transplantation (ISHLT). Criteria were revised to reflect advances in the management of advanced heart failure patients, incorporate evidence from interval landmark trials, and specifically address patients with congenital heart disease, restrictive or infiltrative cardiomyopathy, and chronic infectious disease. Notable updates include frailty assessment, use of mechanical circulatory support as a bridge for candidacy, prioritization of highly sensitized patients, retransplantation for severe chronic allograft vasculopathy, removal of allocation algorithms that allowed for prioritization of higher-status patients within larger geographic areas, lower suggested cutoff values for minimal estimated glomerular filtration rate, assessment of the adequacy of social support in potential transplant candidates, and the role of heart failure prognosis scores in ambulatory patients. Three sections provide guidance on patients that may be less responsive to traditional pharmacologic and device-based therapies and/or have unique challenges with respect to support prior to transplant and posttransplant management. The OPTN policy on allocation of donor hearts was most recently revised in 2018.

Keywords

Listing criteria for heart transplantation Heart transplant candidate International Society for Heart and Lung Transplantation (ISHLT) Advanced heart failure United Network for Organ Sharing (UNOS) Organ Procurement and Transplantation Network (OPTN) Adult heart status Mechanical circulatory support 

List of Abbreviations

AHS

Adult heart status

CMS

Centers for Medicare and Medicaid Services

DSA

Donor-specific area

OPO

Organ procurement organization

Introduction

When a patient develops irreversible dysfunction of an organ, transplantation may be considered. The United Network for Organ Sharing (UNOS) is responsible for managing the national transplant waiting list for the United States and Puerto Rico, the matching of donors to recipients, and maintaining the database that tracks all organ transplant data (History of UNOS 2017). Patients with end-stage heart failure considering a heart transplant need to be evaluated and approved by an accredited cardiac transplant hospital in order to be formally listed with UNOS for potential transplantation. Each adult heart transplant candidate is assigned a status that reflects the candidate’s medical urgency for transplant based on estimated wait-list mortality. Organs are allocated according to wait-list status utilizing a geographic algorithm which was last updated in 2018.

At the 24th Bethesda Conference in 1993, task forces created documents which provided directions toward maximizing the life-saving potential of heart transplantations and provided guidelines for heart transplant candidacy (Mudge et al. 1993). The first International Society of Heart and Lung Transplantation (ISHLT) guidelines were published in 2006 and were subsequently followed by three focused updates addressing evolving areas of importance such as congenital heart disease, restrictive cardiomyopathy, and infectious diseases (Mehra et al. 2006). In 2016, the prior ISHLT guidelines and focused updates were reviewed and revised to include evidence from interval landmark trials and other advances in the management of advanced heart failure patients, resulting in a 10-year update of the ISHLT Listing Criteria for Heart Transplantation (Mehra et al. 2016). Many of the 2006 guidelines recommendations were continued in 2016 without significant change. Notable updates included sections on frailty scores, mechanical circulatory support (MCS) as a bridge for candidacy, highly sensitized patients, severe chronic allograft vasculopathy, the removal of allocation algorithms that allowed for prioritization of higher-status patients within larger geographic areas, a lower suggested cutoff for prohibitive estimated glomerular filtration rate, clarifications on the impact of cardiac resynchronization devices on cardiopulmonary stress testing, assessment of the adequacy of social support in potential transplant candidates, and the role of heart failure prognosis scores in ambulatory patients.

Organ Procurement and Transplantation Network

In 1984, the US Congress passed the National Organ Transplant Act which called for a national network to coordinate the allocation of organs for transplant and collect clinical data about organ donors, transplant candidates, and transplant recipients (United States. Congress. House. Committee on Energy and Commerce. Subcommittee on Health and the Environment. 1984). The United Network for Organ Sharing (UNOS) was incorporated as a private, nonprofit organization in March 1984 and was awarded the initial contract in 1986 to manage the national organ transplant system for the United States. In 2000, the United States Department of Health and Human Services (US DHHS) implemented a final rule establishing a regulatory framework for the structure and operations of the Organ Procurement and Transplantation Network (OPTN) (About the OPTN 2017). UNOS serves as the OPTN under contract with the Health Resources and Services Administration of the US DHHS.

Overview of the 2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation

The 2016 ISHLT listing criteria guidance document is broken into five major sections (Mehra et al. 2016). The first section discusses general considerations of listing patients for heart transplantation and encompasses a formal review and revision of the 2006 guidelines. These revisions are summarized in Table 1. The subsequent three sections focus on the unique aspects of managing patients with restrictive and infiltrative cardiomyopathies, chronic infectious disease, and congenital heart disease. The final section is a brief commentary on marijuana and heart transplantation.
Table 1

Review of changes to ISHLT heart transplant listing guidelines

Section

Change

2016 guidelines

2006 guidelines

1.1. Cardiopulmonary stress testing to guide transplant listing

New: Clarification provided that the use of CRT therapy should not impact peak VO2 interpretation for listing

The presence of a CRT device does not alter the current peak VO2 cutoff recommendations (Class I, LOE: B)

n/a

1.2. Use of heart failure prognosis scores

Update: Change in recommendation to routinely incorporate HF prognosis scores to determine prognosis and guide listing in ambulatory patients rather than use in circumstances of ambiguity

Heart failure prognosis scores should be performed along with cardiopulmonary exercise test to determine prognosis and guide listing for transplantation for ambulatory patients. An estimated 1-year survival as calculated by the Seattle Heart Failure Model (SHFM) of 80% or a Heart Failure Survival Score (HFSS) in the high-/medium-risk range should be considered as reasonable cut points for listing (Class IIb, LOE: C)

In circumstances of ambiguity (e.g., peak VO2 ≤12 and ≤14 ml/kg/ml) a Heart Failure Survival Score (HFSS) may be considered, and it may add discriminatory value to determining prognosis and guide listing for transplantation for ambulatory patients (Class IIb, LOE: C)

1.2. Use of heart failure prognosis scores

New: Statement added that listing patients solely due to poor prognosis score(s) is not appropriate

Listing patients solely on the criteria of heart failure survival prognostic scores should not be performed (Class III, LOE: C)

n/a

1.3. Role of diagnostic right-heart catheterization

Update: Clarification that RHC should be repeated periodically in adults, but no longer specifies a timeline for this reassessment

Right-heart catheterization (RHC) should be performed on all adult candidates in preparation for listing for cardiac transplantation and periodically until transplantation (Class 1, LOE: C)

Right-heart catheterization (RHC) should be performed on all candidates in preparation for listing for cardiac transplantation and annually until transplantation (Class 1, LOE: C)

1.3. Role of diagnostic right-heart catheterization

New: Clarification that routine surveillance RHC is not appropriate in children

Periodic RHC is not advocated for routine surveillance in children (Class III, LOE: C)

n/a

1.3. Role of diagnostic right-heart catheterization

Update: Recommendation regarding patients with irreversible pulmonary hypertension, strengthened and updated, stating that for those who become supported by an LVAD, the lack of reversibility should be reconfirmed 3–6 months post-implantation of the LVAD. Recommendation strengthen increased from IIb to IIA

If medical therapy fails to achieve acceptable hemodynamics and if the left ventricle cannot be effectively unloaded with mechanical adjuncts, including an intra-aortic balloon pump (IABP) and/or left ventricular assist device (LVAD), it is reasonable to conclude that the pulmonary hypertension is irreversible. After LVAD, reevaluation of hemodynamics should be done after 3–6 months to ascertain reversibility of pulmonary hypertension (Class IIA, LOE: C)

If medical therapy fails to achieve acceptable hemodynamics, and if the left ventricle cannot be effectively unloaded with mechanical adjuncts, including an intra-aortic balloon pump (IABP) and/or left ventricular assist device (LVAD), it is reasonable to conclude that the pulmonary hypertension is irreversible (Class IIb, LOE: C)

1.4.1. Age, obesity, and cancer

Update: Removal of reference to “alternate-type program” for older candidates

Carefully selected patients >70 years of age may be considered for cardiac transplantation (Class IIb, LOE: C)

Carefully selected patients >70 years of age may be considered for cardiac transplantation. For centers considering these patients, the use of an alternate-type program (i.e., use of older donors) may be pursued (Class IIb, LOE: C)

1.4.1. Age, obesity, and cancer

Update: The recommended upper limit of acceptable BMI for listing patients increased from 30 to 35 kg/m2, as well as removal of percent ideal body weight guidelines

Pretransplant body mass index (BMI) >35 kg/m2 is associated with a worse outcome after cardiac transplantation. For such obese patients, it is reasonable to recommend weight loss to achieve a BMI of ≤35 kg/m2 before listing for cardiac transplantation (Class IIa, LOE: C)

Overall, pretransplant BMI >30 kg/m2 or percent ideal body weight (PIBW) >140% is associated with poor outcome after cardiac transplantation. For obese patients, it is reasonable to recommend weight loss to achieve a BMI of <30 kg/m2 or percent BMI of <140% of target before listing for cardiac transplantation (Class IIa, LOE: C)

1.4.2. Diabetes, renal dysfunction, and peripheral vascular disease

Update: Addition of a second unit of measurement for glycosolated hemoblobin for assessing persistent glycemic control of diabetes, with clarification that HbA1C >58 mmol/mol or >7.5% be a relative contraindication to listing

Diabetes with end-organ damage (other than non-proliferative retinopathy) or persistent poor glycemic control (glycosylated hemoglobin [HbA1c] 7.5% or 58 mmol/mol) despite optimal effort is a relative contraindication for transplant (Class IIa, LOE: C)

Diabetes with end-organ damage other than non-proliferative retinopathy or poor glycemic control (glycosylated hemoglobin [HbA1c] 7.5%) despite optimal effort is a relative contraindication for transplant (Class IIa, LOE: C)

1.4.2. Diabetes, renal dysfunction, and peripheral vascular disease

Update: Lower limit for acceptable eGFR for listing lowered from 40 ml/min/1.73 m2 to 30 ml/min/1.73 m2

Renal function should be assessed using estimated glomerular filtration rate (eGFR) or creatinine clearance under optimal medical therapy. Evidence of abnormal renal function should prompt further investigation, including renal ultrasonography, estimation of proteinuria, and evaluation for renal arterial disease, to exclude intrinsic renal disease. It is reasonable to consider the presence of irreversible renal dysfunction (eGFR <30 ml/min/1.73 m2) as a relative contraindication for heart transplantation alone (Class IIa, LOE: C)

Renal function should be assessed using estimated glomerular filtration rate (eGFR) or creatinine clearance under optimal medical therapy. Evidence of abnormal renal function should prompt further investigation, including renal ultrasonography, estimation for proteinuria, and evaluation for renal arterial disease, to exclude intrinsic renal disease. It is reasonable to consider the presence of irreversible renal dysfunction (eGFR <40 ml/min/1.73 m2) as a relative contraindication for heart transplantation alone (Class IIa, LOE: C)

1.4.2. Diabetes, renal dysfunction, and peripheral vascular disease

Update: Change to state that clinically severe symptomatic cerebrovascular disease may be considered a contraindication to transplantation without the additional requirement that it “… is not amenable to revascularization”

Clinically severe symptomatic cerebrovascular disease may be considered a contraindication to transplantation. Peripheral vascular disease may be considered a relative contraindication for transplantation when its presence limits rehabilitation and revascularization is not a viable option (Class IIb, LOE: C)

Clinically severe symptomatic cerebrovascular disease, which is not amenable to revascularization, may be considered a contraindication to transplantation. Peripheral vascular disease may be considered as a relative contraindication for transplantation when its presence limits rehabilitation and revascularization is not a viable option (Class IIb, LOE: C)

1.4.3. Assessment of frailty

NEW: Addition of a subsection that highlights the importance of evaluating frailty in potential transplant candidates.

Assessment of frailty (3 of 5 possible symptoms, including unintentional weight loss of ≥10 pounds within the past year, muscle loss, fatigue, slow walking speed, and low levels of physical activity) could be considered when assessing candidacy (Class IIb, LOE: C)

n/a

1.4.4. Mechanical circulatory support for bridge to candidacy

New: Addition of a subsection that highlights the role for using mechanical circulatory support as a bridge to candidacy for patients with potentially reversible or treatable comorbidities

Use of mechanical circulatory support should be considered for patients with potentially reversible or treatable comorbidities, such as cancer, obesity, renal failure, tobacco use, and pharmacologically irreversible pulmonary hypertension, with subsequent reevaluation to establish candidacy (Class IIb, LOE: C)

n/a

1.5.3. Psychosocial evaluation

New: Additional clause stating that inadequate social support for outpatient compliance may be regarded as a relative contraindication to listing, added to section addressing severe cognitive-behavioral disabilities or dementia

Any patient for whom social supports are deemed insufficient to achieve compliant care in the outpatient setting may be regarded as having a relative contraindication to transplant (Class IIa, LOE: C)

n/a

1.5.3. Psychosocial evaluation

Update: Clarification provided as to the rational behind the recommendation not to list patients with severe cognitive-behavioral disabilities or dementia

The benefit of heart transplantation in patients with severe cognitive-behavioral disabilities or dementia (e.g., self-injurious behavior, inability to ever understand and cooperate with medical care) has not been established and has the potential for harm, and, therefore, heart transplantation cannot be recommended for this subgroup of patients (Class IIa, LOE: C)

Mental retardation or dementia may be regarded as a relative contraindication to transplantation (Class IIa, LOE: C)

1.7. Dynamic listing and new donor allocation algorithms

Update: Recommendation added to monitor heart failure survival prognostic scores in addition to the previously recommended monitoring of cardiopulmonary exercise testing at 3–6 month intervals for outpatient, ambulatory, non-inotropic therapy- dependent transplant candidates

Listed patients in an outpatient, ambulatory, non-inotropic therapy- dependent state should be continually evaluated for maximal pharmacologic and device therapy, including implantable cardioverter defibrillator (ICD) or biventricular pacing, when appropriate. Such patients must be reevaluated at 3- to 6-month intervals with cardiopulmonary exercise testing and heart failure survival prognostic scores to assess their response to therapy and, if they have improved significantly, should be considered for delisting (Class I, LOE: C)

Listed patients who are in an outpatient ambulatory non-inotropic therapy-dependent state should be continually evaluated for maximal pharmacologic and device therapy, including implantable cardioverter defibrillator (ICD) or biventricular pacing, when appropriate. Such patients must be reevaluated at 3- to 6-month intervals with cardiopulmonary exercise testing to assess their response to therapy, and if they have improved significantly, they may be candidates for delisting (Class I, LOE: C)

1.7. Dynamic listing and new donor allocation algorithms

Deletion: Clause calling for alternate allocation algorithm that prioritizes higher-status patients within larger geographic areas removed from guidelines

n/a

Redesigned allocation algorithms should be considered that allow for the prioritization of higher-status patients within larger geographic areas (within accepted safe ischemic time limitations). This practice may reduce deaths on the waiting list by both providing more hearts in a timely fashion to the higher acuity population (Class I, LOE: C)

1.7. Dynamic listing and new donor allocation algorithms

New: Addition of a subsection that states higher prioritization may be appropriate for certain highly sensitized patients

Higher prioritization for highly sensitized patients may be considered due to difficulty obtaining a donor, causing excessive waiting times and an increase in waiting list mortality (Class IIb, LOE: C)

n/a

1.8. Retransplantation

New: Addition of a subsection that states that listing for retransplantation may be appropriate in patients with refractory cardiac allograft dysfunction due to CAV, in the absence of ongoing rejection

Retransplantation is indicated for those patients who develop significant CAV with refractory cardiac allograft dysfunction, without evidence of ongoing rejection (Class IIa, LOE: C)

n/a

LOE level of evidence, CRT cardiac resynchronization therapy, RHC right heart catheterization, LVAD left ventricular assist device, IABP intra-aortic balloon pump, BMI body mass index, HbA1c glycosylated hemoglobin, PIBW percent ideal body weight, eGFR estimated glomerular filtration rate, ICD implantable cardioverter defibrillator

Breakdown of the 2016 ISHLT Listing Criteria

Cardiopulmonary exercise testing (CPET) has been used for decades to guide prognosis and heart transplant listing criteria in ambulatory heart failure patients; however it is continually emphasized that CPET variables should not be the sole criterion for heart transplant listing. Peak VO2 should only be assessed on a maximal CPET, which is defined as one with a respiratory exchange ratio (RER) >1.05 and achievement of an anaerobic threshold on optimal tolerated pharmacologic therapy. The cutoff for peak VO2 to guide listing in patients on a beta-blocker should be ≤12 ml/kg/min or ≤14 ml/kg/min in patients intolerant of a beta-blocker (Mancini et al. 1991; Peterson et al. 2003). As an alternative option for women and younger adults (<50 years), the percent of predicted (≤50%) peak Vo2 can be used. In obese patients, those with a body mass index >30 kg/m2 and a lean body mass-adjusted peak VO2 <19 ml/kg/min can be considered. For patients who are unable to complete a maximal CPET, use of ventilation equivalent of carbon dioxide (VE/VCO2) slope of >35 can be considered a determinant for listing based on evidence that the lowest VE/VCO2 ratio is additive to the prognostic power of conventional CPET variables (Myers et al. 2009; Arena et al. 2004).

Heart failure prognosis scores in conjunction with CPET should be performed to determine prognosis and guide listing in ambulatory patients, but also should not be the sole criterion for listing a patient. The recommended prognostic models include the Seattle Heart Failure Model and Heart Failure Survival Score.

Right heart catheterization (RHC) is recommended on all adult candidates prior to listing for cardiac transplantation and should be periodically repeated until transplantation. The specific recommendation to repeat RHC every 3–6 months was removed as it was felt that programs should individualize the timing based on the individual. More frequent RHC is recommended in patients with reversible pulmonary hypertension or worsening heart failure symptoms, and less frequent RHC may be considered in patients with durable left ventricular assist devices (LVADs) as a bridge to transplant (Houston et al. 2015). To clarify reversibility of elevated pulmonary pressures, an acute vasodilator challenge using agents such as intravenous nitroprusside, inhaled nitric oxide, or intravenous milrinone is recommended for patients with elevated pulmonary artery systolic pressures (≥50 mmHg) and either elevated transpulmonary gradient (≥15) or pulmonary vascular resistance (>3 Wood units) in the setting of normal systolic arterial blood pressure (>85 mmHg). If an acute vasodilator challenge is unsuccessful, hospitalization for continued monitoring and an attempt to optimize with diuretics, inotropes, and vasoactive agents are recommended, possibly with the addition of an intra-aortic balloon pump and/or left ventricular assist device if additional unloading is necessary. In children, periodic RHC is not advocated for routine surveillance (Class III, Level of Evidence: C).

Several specific comorbidities have been identified as having significant implications for heart transplant listing, including advanced age, obesity, malignancy, diabetes, renal dysfunction, peripheral vascular disease, frailty, tobacco use, illicit substance abuse, and psychosocial limitations. With respect to age, patients should be considered for cardiac transplantation if they are ≤70 years of age, while carefully selected patients >70 years of age may be considered. The caveat in the 2006 listing criteria that suggested the option of an alternate-type program (i.e., use of older donors) was removed in the 2016 update as it was felt to be unnecessary and confusing. The recommendation for a formal assessment of frailty was included in the 2016 criteria as a potential consideration when assessing candidacy. It was considered an evolving metric as some measures of frailty may be responsive to advanced heart failure therapies, while others are not, and received a Class IIb, Level of Evidence C strength recommendation.

In the 2016 guidelines, a target BMI <35 kg/m2 for listing was recommended, which was less restrictive than the recommended target of a BMI <30 kg/m2 from the 2006 guidelines. This change was supported by evidence that having a BMI >35 kg/m2 has been associated with longer wait time, decreased likelihood of finding a suitable donor, and possible increased posttransplant morbidity and mortality (Mehra et al. 2016; Weiss et al. 2009; Russo et al. 2010). The guidelines recommend that obese patients be counseled on weight loss to achieve a BMI <35 kg/m2 prior to being listing (Mehra et al. 2016).

The presence of additional end-stage disease processes or significant medical conditions is often considered relative contraindications for isolated heart transplant listing. Diabetes mellitus is considered a relative contraindication for transplant if, despite optimal effort, there is persistent poor glycemic control (HbA1C >7.5% or 58 mmol/mol) or evidence of end-organ damage other than non-proliferative retinopathy. The presence of irreversible renal dysfunction (eGFR <30 ml/min/1.73 m2) is a relative contraindication for heart transplantation alone, although a combined heart/kidney transplantation may be considered. Cerebrovascular disease may be considered a contraindication to transplantation if clinically severe and symptomatic. Peripheral vascular disease may be considered a relative contraindication for transplantation when its presence limits rehabilitation and revascularization is not a viable option.

Patients with a history of neoplasm should be evaluated in collaboration with oncology specialists and can be considered for listing for heart transplantation when tumor recurrence is low based on tumor type, response to therapy, and negative metastatic work-up. No arbitrary time period for observation is recommended given the diverse range of neoplasms.

For patients being considered for heart transplant listing with potentially treatable or reversible comorbidities, consideration of the use of MCS is recommended as a potential bridge to candidacy. Potential opportunities for MCS with subsequent reevaluation to establish candidacy could include patients with nonfatal cancer diagnoses, obesity, tobacco use, moderate renal failure, and pharmacologically irreversible pulmonary hypertension.

Behavioral and psychosocial health have a significant impact on transplant candidacy and outcomes. Active tobacco smoking is considered a relative contraindication to transplantation as active tobacco smoking during the previous 6 months is a risk factor for poor outcomes after transplantation (Corbett et al. 2012; Khanna et al. 2009). Posttransplant smoking is also associated with worse outcomes, including higher odds of having new posttransplant cardiovascular disease, nonskin malignancies, shorter survival time, and increased mortality (Duerinckx et al. 2016). Active substance abuse, including alcohol, is considered an absolute contraindication to listing (Class III, Level of Evidence C), and a structured rehabilitative program may be considered in those with a recent (24-month) history of alcohol abuse. A formal psychosocial assessment should be performed before listing any candidate for transplantation, including an assessment of the patient’s ability to give informed consent and comply with instructions, as well as assessment the support systems in place at home or in the community. As per the 2016 guidelines, heart transplantation is still not recommended for patients with severe cognitive-behavioral disabilities or dementia due to a lack of demonstrated benefit and risk for potential harm (Mehra et al. 2016). Additionally, patients for whom social supports are deemed insufficient to achieve compliant outpatient care may be considered as having a relative contraindication to transplant.

In the 2006 ISHLT listing criteria, Table 3 showed a “Recommended Schedule for Heart Transplant Evaluation.” In the 2016 updated guidelines, this is referred to as a screening grid for pretransplant evaluation, and no changes were recommended; however it was anticipated that transplant programs may need to update their grids based on the new general and special considerations in the 2016 listing criteria.

Additionally, it was specified that ambulatory outpatients who are not dependent on inotropic therapy should be serially evaluated for maximal pharmacologic and device therapy options and undergo periodic reevaluations at 3- to 6-month intervals with CPETs and heart failure survival prognostic scores to assess for interval improvement meriting consideration of delisting. Reallocation algorithms that allowed for prioritization of higher-status patients within larger geographic areas were removed from the listing criteria in 2016. However, consideration was added to afford higher prioritization for highly sensitized patients due to difficulty obtaining a donor, causing excessive waiting times and an increase in waiting list mortality. Retransplantation was also clarified as appropriate for patients with significant chronic allograft vasculopathy without evidence of ongoing rejection.

Special Considerations in the 2016 ISHLT Listing Criteria

Three sections of the 2016 ISHLT Listing Criteria for Heart Transplantation address specific cohorts of patients with advanced heart failure who have phenotypes that may be less responsive to traditional pharmacologic and device-based therapies and/or pose unique challenges for bridging to transplant and posttransplant management.

Section II of the 2016 ISHLT OHT Listing Criteria Guideline discusses patients with restrictive, infiltrative, hypertrophic, or arrhythmogenic right ventricular dysplasia cardiomyopathy. These patients express a phenotype that is usually not characterized by LV dilation and hypokinesis and thus may be less responsive to traditional interventions, including possible intolerance of vasodilator therapies and diuretic adjustments (Yancy et al. 2013). This population is also felt to be difficult to treat with an LVAD due to cavity size and/or biventricular disease processes (Patel et al. 2017; Topilsky et al. 2011). Small LV cavity size may increase the risk of contact between inflow cannulas and the ventricular septum, leading to focal irritation of the septum which is a nidus for life-threatening ventricular arrhythmias or thrombus formation, as well as result in partial or complete obstruction of the inflow cannula causing submaximal support. If MCS is pursued, partial myomectomies to augment cavity size or a total artificial heart may be appropriate in some cases. Inotropes seldom provide significant symptomatic relief and may result in problematic arrhythmias and/or left ventricular outflow tract obstruction (Nicholls 2014). No medical or device therapy has been proven to improve outcomes in RCM, and symptomatic therapy is often of limited efficacy. If no treatable etiology is identified, heart transplantation may be the sole therapeutic option available to improve prognosis and symptoms. In cases of cardiac amyloidosis, guidelines specifically state that extracardiac organs must be carefully evaluated for involvement of amyloid prior to considering heart transplantation. Concern was high that restrictive, infiltrative, hypertrophic, and arrhythmogenic phenotypes were associated with increased morbidity and mortality with the prior listing criteria due to limited advanced therapy options for supporting patients with lethal dysthymias and non-dilated ventricles leading to low priority status and long wait times. The 2018 update of Policy 6, the allocation of hearts and heart-lungs, attempted to address these concerns with multiple options for higher status for patients not supported by inotropes or durable MCS, including the option for listing as an outpatient at status 4 if one of six criteria is met.

Screening and management of advanced heart failure patients with certain chronic or latent infectious diseases is covered in Section III of the guidelines, specifically human immunodeficiency viral (HIV) infection, Chagas disease, tuberculosis, and hepatitis B and C viral (HBV and HCV) infections. As of 2016, patients with HIV infection, HBV, HCV, Chagas disease, or latent tuberculosis may be considered as potential candidates, provided there is demonstrated clinical stability and adherence to specified patient management principles. Selected HIV-positive candidates may be considered for heart transplantation if they have no active or prior opportunistic infections, are clinically stable, are compliant on combination antiretroviral therapy (cART) for >3 months, have undetectable HIV RNA, and have CD4 counts 4200 cells/μl for >3 months.

Due to migration and travel, Chagas disease is now a worldwide health problem. Heart transplantation is the recommended therapy for heart failure related to Chagas disease, despite the elevated risk of reactivation posttransplantation (18–22%). Universal screening for Trypanosoma cruzi infection should be performed in all heart transplant candidates with significant exposure to Latin America through birth or travel as close monitoring for reactivation posttransplantation may be necessary.

Universal screening for latent tuberculosis infection (LTBI) is recommended for all heart transplant candidates to minimize the risk of reactivation posttransplantation, which is associated with significant challenges in management as well as high mortality (Subramanian et al. 2013). Patients with confirmed LTBI should be treated for 6–9 months; however the guidelines specify that this treatment should not interfere with the timing of transplantation.

Vaccination and/or revaccination are suggested before heart transplantation if candidates lack evidence of seroprotection for vaccine preventable diseases on screening serology. Heart transplant candidates should be screened for chronic or resolved HBV and HCV infections. Owing to differential therapeutic responses, determination of HCV genotype is recommended. If resolved or prior inactive HBV or HCV infection is confirmed, serial monitoring at 3-month intervals while listed is recommended, as well as repeat screening at the time of transplantation. In patients with chronic HCV or HBV infection, clinical, radiologic, or biochemical signs of cirrhosis, portal hypertension, or hepatocellular carcinoma are contraindications to heart transplantation.

Advanced heart failure in patients with congenital heart disease (CHD) is addressed in Section IV of the 2016 guidelines. Patients with CHD may require transplantation in the absence of overt heart failure due to unique anatomic and physiologic issues such as failing Fontan circulation. Bridging these candidates to transplantation can be challenging, and timely transplantation can be challenged by sensitization. Patients with “hemodynamically significant” CHD can be listed as an outpatient at status 4 as per the 2018 updated UNOS policy. Clear delineation of intrathoracic anatomy within the chest can identify aortopulmonary collaterals in patients with single ventricle physiology which may need to be addressed prior to transplantation, and anatomic details may aid in planning bypass cannulation and surgical strategies.

Marijuana

The last section of the 2016 guidelines is Section V, which briefly reviews the use of marijuana and eligibility for heart transplantation. Marijuana use is identified as a highly controversial area with little evidence to guide decision-making. No recommendations by the ISHLT are provided; however the guidelines advise caution in considering the listing of candidates unable to give up the use of cannabis or those with heavy use which has impaired cognitive ability and could lead to challenges with medication adherence, infectious complications, and/or interactions with immune suppression.

Heart Transplant Allocation System

Donor heart management is coordinated by UNOS and local OPTN, and donor hearts are offered to listed heart transplant candidates based on medical urgency, blood type compatibility, and geographic sharing. Potential candidates are assigned a status that reflects their medical urgency and appropriateness for transplantation. In 2016, the Thoracic Organ Transplantation Committee of the Organ Procurement and Transplantation Network (OPTN) proposed modifications to the heart allocation system to improve stratification of candidates (“Adult Heart Allocation Changes 2016”). The last revisions had been in 2006, and multiple concerns were raised, including frequent use of exemption requests for uplisting, grouping of candidates with disparate estimated wait-list mortality together in the same status, and potential inequalities in allocation related to the geographic sharing scheme. After community-wide discussion and debate, the system was updated in 2018 with the expectation and goal of improving overall wait-list morality rates and transplant rates for the most medically urgent candidates without negatively impacting overall posttransplant mortality rates or wait-list mortality rates for candidates in lower urgency statuses. Notable changes included increased wait-list statuses to more accurately stratify heart transplant candidates based on estimated wait-list mortality (Fig. 1) and a redesign of the organ distribution scheme to provide the most medically urgent candidates access to donors from a broader geographic area.
Fig. 1

Adult Heart Allocation Criteria for Medical Urgency. An infographic overview of the status criteria for the UNOS adult heart and heart-lung allocation system. (Organ Procurement and Transplantation Network Policies 2019)

In the new (current) system, candidates who are at least 18 years of age can be assigned to an adult heart status (AHS) ranging from 1 to 6 for highest to lowest estimated risk for wait-list mortality, with multiple different clinical scenarios to qualify for each status (Organ Procurement and Transplantation Network Policies 2019). Listing statuses are temporary with varied duration and renewal requirements. Listed candidates who are temporarily not appropriate for heart transplant are listed as status 7. Changes in listing status are to be reported and/or requested from the OPTN. Heart candidates less than 18 years of age at the time of registration may be assigned pediatric status 1A, pediatric status 1B, pediatric status 2, or inactive status. Candidates listed as pediatric remain eligible for pediatric status regardless of age until removed from the waiting list.

Adult candidates may satisfy the requirements to be listed as status 1 if supported by veno-extracorporeal membrane oxygenation (VA ECMO) or a non-dischargeable, surgically implanted, non-endovascular biventricular support device. Criteria for status 2 ranges from support by various MCS systems including but not limited to total artificial heart, biventricular assist devices, intra-aortic balloon pump (IABP), and an MCSD with high risk for life-threatening malfunctioning or the presence of recurrent or sustained ventricular tachycardia or fibrillation. Requirements for AHS 3 include but are not limited to support by a high-dose inotrope, multiple inotropes, an MCSD with complication, prolonged VA ECMO or IABP, and a subset of MCSD. Eligibility for AHS 4 includes support by inotropes without daily hemodynamic monitoring or LVAD, history of prior cardiac transplant, or a high-risk phenotype not easily supported by MCSD or inotropes. Candidates are listed for AHS 5 if they are listed for more than one organ at the same hospital, and AHS 6 includes all other remaining active candidates.

When compared to the prior UNOS status categories, the current statuses 1–3 were the previous 1A status, status 4 was the previous 1B or 2 status, and statuses 5–6 were the previous status 2. The new criteria do increase the status ranking of patients with restrictive and congenital cardiomyopathy (previously status 2 if ambulatory without inotropes). Patients with durable LVADs again have 30 discretionary time as status 3 (previously 1A), and the previous exception criteria for LVADs as status 1A are more restrictive in allowing patients to move up to a status 3.

Within each heart status and geographical zone classification, hearts are first allocated to primary blood type candidates then to secondary blood type candidates in a sequential order reflecting acuity of listing and geographical proximity within predefined regions, further stratified by wait-list time (Tables 2 and 3) (Organ Procurement and Transplantation Network Policies 2019). The OPTN contractor will only offer organs from deceased donors with mismatched antigens equal to or less than the maximum specified by a transplant program. Wait-list time is calculated by status and time accrued at a status; time accrued at one status does not transfer or get lost with status upgrades or downgrades.
Table 2

OPTN allocation zones: Five concentric bands or zones of geographical areas are used in the allocation of thoracic organs

DSA

The geographic area designated by the Centers for Medicare and Medicaid Services (CMS) that is served by one organ procurement organization (OPO), one or more transplant hospitals, and one or more donor hospitals

Zone A

Includes all transplant hospitals within 500 nautical miles of the donor hospital but outside of the donor hospital’s DSA

Zone B

All transplant hospitals within 1000 nautical miles of the donor hospital but outside of Zone A and the donor hospital’s DSA

Zone C

All transplant hospitals within 1500 nautical miles of the donor hospital but outside of Zone B and the donor hospital’s DSA

Zone D

All transplant hospitals within 2500 nautical miles of the donor hospital but outside of Zone B and the donor hospital’s DSA

Zone E

All transplant hospitals more than 2500 nautical miles from the donor hospital

This table defines the geographical system utilized for distribution of solid organs for transplantation. (Borrowed from the OPTN Policies, Effective Date: 3/30/2017, Section “Administrative Rules and Definitions”) (Organ Procurement and Transplantation Network Policies 2019)

Table 3

OPTN adult heart allocation: Overview of the allocation sequence for offering of hearts from deceased donors of at least 18 years of age

Allocation order

Candidates’ listing region

Candidate criteria

1

OPO’s DSA

Adult or pediatric status 1A and primary blood type match with the donor

2

OPO’s DSA

Adult or pediatric status 1A and secondary blood type match with the donor

3

OPO’s DSA

Adult or pediatric status 1B and primary blood type match with the donor

4

OPO’s DSA

Adult or pediatric status 1B and secondary blood type match with the donor

5

Zone A

Adult or pediatric status 1A and primary blood type match with the donor

6

Zone A

Adult or pediatric status 1A and secondary blood type match with the donor

7

Zone A

Adult or pediatric status 1B and primary blood type match with the donor

8

Zone A

Adult or pediatric status 1B and secondary blood type match with the donor

9

OPO’s DSA

Adult or pediatric status 2 and primary blood type match with the donor

10

OPO’s DSA

Adult or pediatric status 2 and secondary blood type match with the donor

11

Zone B

Adult or pediatric status 1A and primary blood type match with the donor

12

Zone B

Adult or pediatric status 1A and secondary blood type match with the donor

13

Zone B

Adult or pediatric status 1B and primary blood type match with the donor

14

Zone B

Adult or pediatric status 1B and secondary blood type match with the donor

15

Zone A

Adult or pediatric status 2 and primary blood type match with the donor

16

Zone A

Adult or pediatric status 2 and secondary blood type match with the donor

This table is an abbreviated overview of the algorithm for allocation of hearts from deceased donors at least 18 years old. The full version of all 36 options is available in the (OPTN Policies, Effective Date: 3/30/2017 in the Section “Allocation of Hearts and Heart-Lungs”) (Organ Procurement and Transplantation Network Policies 2019)

Conclusion

UNOS is the OPTN that manages the heart transplantation matching and allocation system for the United States and Puerto Rico (Organ Procurement and Transplantation Network Policies 2019). The ISHLT published updated International Listing Criteria for Heart Transplantation, which were revised from the 2006 guidelines to reflect progress in the management of advanced heart failure patients and specifically address evolving areas of importance including congenital heart disease, restrictive cardiomyopathy, and chronic infectious diseases, such as HIV (Mehra et al. 2006, 2016). Many prior recommendations were continued without significant change; however notable updates include recommendations on frailty assessment, use of mechanical circulatory support as a bridge for candidacy, prioritization of highly sensitized patients, retransplantation for severe chronic allograft vasculopathy, removal of allocation algorithms that allowed for prioritization of higher-status patients within larger geographic areas, lower suggested cutoff for minimal estimated glomerular filtration rate, assessment of the adequacy of social support in potential transplant candidates, and the role of heart failure prognosis scores in ambulatory patients. The US adult heart allocation system was updated in 2018 with increased stratification of patients based on estimated wait-list mortality and changes designed to enhance access to donor heart offers to those with the highest wait-list mortality in a broader geographic area.

Cross-References

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Center for Advanced Heart Disease & TransplantProvidence Spokane Heart InstituteSpokaneUSA
  2. 2.Advanced Heart Failure ProgramBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA

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