CAM 70308

Heart/Lung Transplant

Category:Surgery   Last Reviewed:January 2019
Department(s):Medical Affairs   Next Review:January 2020
Original Date:July 1996    

Description:
Heart/lung transplantation involves a coordinated triple operative procedure consisting of procurement of a donor heart/lung block, excision of the heart and lungs of the recipient, and implantation of the heart and lungs into the recipient. Heart/lung transplantation refers to the transplantation of one or both lungs and heart from a single cadaver donor.

For individuals who have end-stage cardiac and pulmonary disease who receive combined heart/lung transplant, the evidence includes case series and registry data. Relevant outcomes are overall survival, symptoms, morbid events, and treatment-related morbidity and mortality. The available literature describes outcomes after heart/lung transplantation. Given the exceedingly poor expected survival rates without transplantation, this evidence is sufficient to demonstrate that heart/lung transplantation provides a survival benefit in appropriately selected patients. Transplant may be the only option for some patients with end-stage cardiopulmonary disease. Heart/lung transplant is contraindicated for patients in whom the procedure is expected to be futile due to comorbid disease or for whom posttransplantation care is expected to worsen comorbid conditions significantly. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. 

For individuals who have a combined heart/lung transplant complicated by graft failure or severe dysfunction of the heart/lung and who receive a combined heart/lung retransplant, the evidence includes case series and registry data. Relevant outcomes are overall survival, symptoms, morbid events, and treatment-related morbidity and mortality. A very limited amount of data has suggested that, after controlling for confounding variables, survival rates after primary and repeat heart/lung transplants are similar. Findings are not conclusive due to the small number of cases of repeat heart/lung transplants reported in the published literature. Repeat heart/lung transplantation is, however, likely to improve outcomes in patients with a prior failed transplant who meet the clinical criteria for heart/lung transplantation. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

Background 
Heart/Lung Candidates Requiring Transplantation 
Most heart/lung transplant recipients have Eisenmenger syndrome (37%), followed by idiopathic pulmonary artery hypertension (28%) and cystic fibrosis (14%). Eisenmenger syndrome is a form of congenital heart disease in which systemic-to-pulmonary shunting leads to pulmonary vascular resistance. It is possible that pulmonary hypertension could lead to a reversal of the intracardiac shunting and inadequate peripheral oxygenation or cyanosis.1. 

Treatment 
Combined heart/lung transplantation is intended to prolong survival and improve function in patients with end-stage cardiac and pulmonary diseases. Due to corrective surgical techniques and improved medical management of pulmonary hypertension, the total number of patients with Eisenmenger syndrome has seen a decline in recent years. Additionally, heart/lung transplants have not increased appreciably, but for other indications, it has become more common to transplant a single or double lung and maximize medical therapy for heart failure, rather than perform a combined transplant. For those indications, patient survival rates following heart/lung transplantations are similar to lung transplant rates. Bronchiolitis obliterans syndrome is a major complication. One-, 5-, and 10-year patient survival rates for heart/lung transplants performed between 1982 and 2014 were estimated at 63%, 45%, and 32%, respectively.2.

In 2017, 29 individuals received heart/lung transplants in the United States. As of April 2018, 51 patients were on the waiting list for heart/lung transplants.3.

Related Policies:
70307  Lung and Lobar Lung Transplant
70309  Heart Transplant

Policy:
Heart/lung transplantation may be considered MEDICALLY NECESSARY for carefully selected patients with end-stage cardiac and pulmonary disease including, but not limited to, one of the following diagnoses:

  • Irreversible primary pulmonary hypertension with heart failure
  • Nonspecific severe pulmonary fibrosis, with severe heart failure
  • Eisenmenger complex with irreversible pulmonary hypertension and heart failure
  • Cystic fibrosis with severe heart failure
  • Chronic obstructive pulmonary disease with heart failure
  • Emphysema with severe heart failure
  • Pulmonary fibrosis with uncontrollable pulmonary hypertension or heart failure

Heart/lung retransplantation after a failed primary heart/lung transplant may be considered MEDICALLY NECESSARY in patients who meet criteria for heart/lung transplantation.

Heart/lung transplantation is considered INVESTIGATIONAL in all other situations.

Policy Guidelines:
Potential contraindications, subject to the judgment of the transplant center:

  1. Known current malignancy, including metastatic cancer
  2. Recent malignancy with high risk of recurrence
  3. Untreated systemic infection making immunosuppression unsafe, including chronic infection
  4. Other irreversible end-stage disease not attributed to heart or lung disease
  5. History of cancer with a moderate risk of recurrence
  6. Systemic disease that could be exacerbated by immunosuppression
  7. Psychosocial conditions or chemical dependency affecting ability to adhere to therapy

When the candidate is eligible to receive a heart in accordance with United Network for Organ Sharing (UNOS) guidelines for cardiac transplantation, the lung(s) shall be allocated to the heart-lung candidate from the same donor. When the candidate is eligible to receive a lung in accordance with the UNOS Lung Allocation System (LAS), the heart shall be allocated to the heart-lung candidate from the same donor if no suitable Status 1A isolated heart candidates are eligible to receive the heart. Status 1A is described below.(3)

Cardiac-Specific
The United Network for Organ Sharing (UNOS) prioritizes donor thoracic organs according to the severity of illness as follows:

Status 1A
A patient is admitted to the listing transplant center hospital and has at least 1 of the following devices or therapies in place:

  1. Mechanical circulatory support for acute hemodynamic decompensation that includes at least 1 of the following:
    1. Left and/or right ventricular assist device implanted
    2. Total artificial heart
    3. Intra-aortic balloon pump
    4. Extracorporeal membrane oxygenator (ECMO)
  2. Mechanical circulatory support
  3. Mechanical ventilation
  4. Continuous infusion of inotropes and continuous monitoring of left ventricular filling pressures
  5. If criteria a, b, c and d are not met, such status can be obtained by application to the applicable Regional Review Board

Status 1B
A patient has at least 1 of the following devices or therapies in place:

  1. Left and/or right ventricular device implanted
  2. Continuous infusion of intravenous inotropes

A patient who does not meet Status 1A or 1B is listed as Status 2.

Status 7 patients are considered temporarily unsuitable to receive a thoracic organ transplant:

Benefit Application
BlueCard®/National Account Issues
Heart/lung transplants should be considered for coverage under the Transplant benefit.

What is covered under the scope of the Human Organ Transplant (HOT) benefit needs to be considered. Typically, the following are covered under the HOT benefit:

  • Hospitalization of the recipient for medically recognized transplants from a donor to a transplant recipient
  • Evaluation tests requiring hospitalization to determine the suitability of both potential and actual donors, when such tests cannot be safely and effectively performed on an outpatient basis
  • Hospital room, board and general nursing in semi-private rooms
  • Special care units, such as coronary and intensive care
  • Hospital ancillary services
  • Physicians’ services for surgery, technical assistance, administration of anesthetics and medical care
  • Acquisition, preparation, transportation and storage of organ
  • Diagnostic services
  • Drugs that require a prescription by federal law

Expenses incurred in the evaluation and procurement of organs and tissues are benefits when billed by the hospital. Included in these expenses may be specific charges for participation with registries for organ procurement, operating rooms, supplies, use of hospital equipment and transportation of the tissue or organ to be evaluated.

Administration of products with a specific transplant benefit needs to be defined as to:

  • When the benefit begins (at the time of admission for the transplant or once the patient is determined eligible for a transplant, which may include tests or office visits prior to transplant).
  • When the benefit ends (at the time of discharge from the hospital or at the end of required follow-up, including the immunosuppressive drugs administered on an outpatient basis).

Coverage usually is not provided for:

  • HOT services for which the cost is covered/funded by governmental, foundation or charitable grants
  • Organs sold rather than donated to the recipient
  • An artificial organ

Rationale
This evidence review was created in July 1996 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through June 7, 2018. 

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are length of life, quality of life, and ability to function—including benefits and harms. Every clinical condition has specific outcomes that are important to patients and to managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of a technology, 2 domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one or more intended clinical uses of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Due to the nature of the disease condition, there are no randomized controlled trials comparing heart/lung transplant with alternatives. Systematic reviews are based on case series and registry data. The extant randomized controlled trials compare surgical technique, infection prophylaxis, and immunosuppressive therapy and are not germane to this evidence review.

Prioritization of Candidates 
Patients who are eligible for heart/lung transplantation can be listed under both the heart and lung allocation systems in the United States. In 2005, United Network for Organ Sharing (UNOS) changed the method by which lungs were allocated, from one based on length of time on the waiting list to a system that incorporates the severity of the patient’s underlying disease, as well as likelihood of survival.4. However, it has been noted that the individual systems underestimate the severity of illness in patients with both end-stage heart and lung failure, and modification of the lung allocation score can be appealed for patients who meet the following criteria5. :

  • Deterioration of optimal therapy, and
  • Right arterial pressure greater than 15 mm Hg or
  • Cardiac index less than 1.8 L/min/m2.

Specific criteria for prioritizing donor thoracic organs for transplant are provided by the Organ Procurement and Transplantation Network (OPTN) and implemented through a contract with UNOS.6.

Yusen et al (2016) analyzed data on heart/lung transplantations performed among adults between 1982 and 2015 using the registry of the International Society for Heart and Lung Transplantation (ISHLT).2. Among the 3397 heart/lung transplant recipients for whom the diagnosis was reported, 35% had congenital heart disease (CHD), 27% had pulmonary arterial hypertension, and 14% had cystic fibrosis as the primary indication. There has been a shift in indications for heart/lung transplantation over time. From 2004 to 2015, CHD (35%), pulmonary arterial hypertension (27%), and cardiomyopathy (11%) were the three most common indications for heart/lung transplantation. Of the 883 heart/lung transplant recipients during 2004 and 2015, 36% were 18 to 34 years old, 40% were 35 to 49 years old, and 24% were 50 years or older. 

Pediatric Considerations 
In an analysis of data from the OPTN, Spahr and West (2014) provided indications for pediatric heart/lung transplantation.7. The number of pediatric heart/lung transplants has decreased in recent years (56 cases from 1993 to 1997; 32 cases from 2008 to 2013). The 3 most common indications for pediatric heart/lung transplant were primary pulmonary hypertension (n=55), CHD (n=37), and Eisenmenger syndrome (n=30). However, while 30 children received a heart/lung transplant for Eisenmenger syndrome through 2002, no transplants for this syndrome have been performed since then. Pediatric heart/lung transplants have also been performed for other indications, including alpha1-antitrypsin deficiency, pulmonary vascular disease, cystic fibrosis, and dilated cardiomyopathy.

Using ISHLT Registry data, Benden et al (2012) reported on pediatric heart/lung transplant data collected through June 2011.8. Overall survival rates after heart/lung transplants are comparable in children (median half-life, 4.7 years) and adults (median half-life, 5.3 years). For pediatric heart/lung transplants performed between 1990 and 2010, the 5-year survival rate was 49%. The 2 leading causes of death in the first year after transplantation were non-cytomegalovirus infection and graft failure. Beyond 3 years posttransplant, the major cause of death was bronchiolitis obliterans syndrome. An updated report by Benden et al (2014) on pediatric lung and heart/lung transplant from the same registry did not include updated data on pediatric heart/lung transplants due to the small number of patients available.9. 

Initial Combined Heart/Lung Transplant 
Clinical Context and Therapy Purpose 
The purpose of combined heart/lung transplant in patients who have end-stage cardiac and pulmonary disease is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does combined heart/lung transplant improve the net health outcome in patients who have end-stage cardiac and pulmonary disease?

The following PICOTS were used to select literature to inform this review. 

Patients 
The relevant population of interest is patients with end-stage cardiac and pulmonary disease. 

Interventions 
The therapy being considered is combined heart/lung transplant. 

Comparators 
The following practices are currently being used to make decisions about end-stage cardiac and pulmonary disease: medical management, double-lung transplant, and single-lung transplant. 

Outcomes 
The general outcomes of interest are overall survival, graft failure, improved function, and adverse events (eg, infections). 

Timing 
Follow-up after surgery focuses on monitoring for graft failure. Long-term follow-up can continue out to 3 to 5 years and beyond. 

Setting 
Heart and lung transplants are provided in a hospital setting with specialized staff and equipped to perform the surgical procedure.

Registry Studies and Case Series
Yusen et al (2016) reported on the survival of adult heart/lung transplant recipients using the ISHLT database.2. Among the 3775 primary heart/lung transplants performed during 1982 and 2014, the 3- month, 1-year, 3-year, 5-year, and 10-year survival rates were 71%, 63%, 52%, 45%, and 32%, respectively. The overall median survival during this period (1982-2014) was 3.4 years. Those who survived to 1 year had a conditional median survival of 10.3 years. Survival improved over time, with a median survival of 2.1 years for patients (n=1596) who received the transplant between 1982 and 1993, 3.9 years for patients (n=1392) between 1994 and 2003, and 5.8 years for patients between 2004 and 2014 (n=843) (p<0.05 for all pairwise comparisons). Heart/lung transplant recipients in the 2004 to 2014 group had a median conditional survival beyond 10 years. Compared with lung-only transplantation (median conditional survival, 8.0 years), heart/lung transplant recipients had a better long-term survival (median conditional survival, 10.3 years).

Hill et al (2015) compared survival following heart/lung transplantation with double-lung transplantation for idiopathic pulmonary arterial hypertension among adult transplant recipients in the Scientific Registry of Transplant Recipients database during 1987 and 2012.10. Among the 928 idiopathic pulmonary arterial hypertension patients, 667 underwent double-lung transplantation, and 261 underwent heart/lung transplantation. Overall, the adjusted survival was similar between double-lung transplantation and heart/lung transplant recipients. However, for recipients hospitalized in the intensive care unit, double-lung transplantation was associated with worse outcomes than heart/lung transplantation recipients (hazard ratio HR., 1.83; 95% confidence interval CI., 1.02 to 3.28).

Jayarajan et al (2014) compared the mortality rates (at 1 month and 5 years posttransplant) of heart/lung transplant recipients who required pretransplant ventilation (n=22) or extracorporeal membrane oxygenation (ECMO; n=15) with controls.11. Median survival times were 10 days, 181 days, and 1547 days among patients with pretransplant ECMO, patients with mechanical ventilator, and the control group, respectively. Patients with pretransplant ECMO had poorer survival than the control group at 30 days (20.0% vs 83.5%) and 5 years (20.0% vs 47.4%; p<0.001). Similarly, patients requiring ventilation prior transplantation had worse survival at 1 month (77.3% vs 83.5%) and 5 years (26.5% vs 47.4%; p<0.001) compared with the control group. The use of ECMO (HR=3.82; 95% CI, 1.60 to 9.12; p=0.003) or mechanical ventilation (HR=2.01; 95% CI, 1.07 to 3.78; p=0.030) as a bridge to transplantation was independently associated with mortality on multivariate analysis. The findings of the study raise concern whether combined heart/lung transplant should be carried out in patients requiring ECMO; further, the findings suggest a need for additional research to improve survival in this high-risk group of patients. 

Pediatric Considerations 
Goldfarb et al (2016) reported on the survival of pediatric lung and heart/lung transplant recipients using the ISHLT database.12.  Among the 698 pediatric heart/lung transplant recipients, median survival was 3.0 years, and conditional median survival was 7.8 years. There was no statistically significant difference in survival by indication, recipient age group, or time period of transplant for pediatric heart/lung transplant recipients.

Keeshan et al (2014) assessed outcomes for pediatric heart/lung transplantation between children who had CHD with and without Eisenmenger syndrome using the UNOS database of  heart/lung transplantations performed from 1987 to 2011.13. Among the 178 pediatric heart/lung transplantations performed during that period, 73 (41%) had cardiac etiologies and 69 (38%) had idiopathic pulmonary arterial hypertension as the primary diagnosis. Among the patients with cardiac etiologies, CHD was the most common diagnosis (n=65). Children with CHD without Eisenmenger syndrome (n=34) had a lower median survival (1.31 years) than children with CHD plus Eisenmenger syndrome (n=31; median survival, 4.80 years; p=0.05). On multivariable analysis, CHD without Eisenmenger syndrome (adjusted HR=1.69; 95% CI, 1.09 to 2.62), younger age (adjusted HR=1.04; 95% CI, 1.01 to 1.08), pretransplant mechanical ventilation (adjusted HR=1.75; 95% CI, 1.01 to 3.06), pretransplant ECMO (adjusted HR=3.07; 95% CI, 1.32 to 7.12), pretransplant panel reactive antibodies (adjusted HR=1.53; 95% CI, 1.06 to 2.20), and transplant era (adjusted HR=1.85; 95% CI, 1.16 to 2.94) were associated with graft failure. 

Section Summary: Initial Heart/Lung Transplant 
Data from transplantation registries have found longer patient survival rates after initial heart/lung transplant among adult and pediatric patients over time. The net benefit of heart transplantation compared with lung-only transplantation is also evident, especially among patients with idiopathic pulmonary arterial hypertension. 

Heart/Lung Retransplantation 
Clinical Context and Therapy Purpose 
The purpose of combined heart/lung retransplant in patients who have had a combined heart/lung transplant complicated by graft failure or severe dysfunction of the heart/lung is to provide a treatment option that is an alternative to or an improvement on existing therapies.

The question addressed in this evidence review is: Does combined heart/lung retransplant improve the net health outcome in patients whose combined heart/lung transplant has been complicated by graft failure or severe dysfunction of the heart/lung?

The following PICOTS were used to select literature to inform this review. 

Patients 
The relevant population of interest is patients with a combined heart/lung transplant complicated by graft failure or severe dysfunction of the heart/lung. 

Interventions 
The therapy being considered is combined heart/lung retransplant. 

Comparators 
The following practices are currently being used to make decisions about a combined heart/lung transplant complicated by graft failure or severe dysfunction of the heart/lung: medical management, double-lung transplant, and single-lung transplant. 

Outcomes 
The general outcomes of interest are overall survival, graft failure, improved function, and adverse events (eg, infections). 

Timing 
Follow-up after surgery focuses on monitoring for graft failure. Long-term follow-up can continue out to 3 to 5 years and beyond. 

Setting 
Heart and lung transplants are provided in a hospital setting with specialized staff and equipped to perform the surgical procedure. 

Registry Studies 
While uncommon, repeat heart/lung transplant procedures have been performed. Yusen et al (2014) reported on outcomes for adult heart/lung transplants, with a focus on retransplantation, using data from the ISHLT Registry.14. From 1982 to 2012, 90 adults had a first heart/lung retransplant after a previous heart/lung transplant. These 90 patients had a median survival of 0.3 years, with unadjusted survival rates of 52%, 43%, 36%, and 27% at 3 months, 1 year, 3 years, and 5 years, respectively. Those who survived to 1 year had a conditional median survival of 7.9 years.

A study by Shuhaiber et al (2008) reviewed data from the UNOS registry.15. They identified 799 primary heart/lung and 19 repeat heart/lung transplants. Using Kaplan-Meier survival analysis, the observed median survival times were 2.08 years after primary transplant and 0.34 years after repeat transplants. In addition, reviewers analyzed survival data in matched pairs of primary and repeat transplant patients, who were matched on a number of potentially confounding demographic and clinical characteristics. Matches were not available for 4 repeat transplant patients. For the 15 repeat transplant patients with primary transplant matches, survival time did not differ significantly between groups. Being on a ventilator was statistically significantly associated with decreased survival time. The main limitation of this analysis was the low number of repeat transplant procedures performed. 

Section Summary: Heart/Lung Retransplant 
Analysis has suggested that patients undergoing heart/lung retransplantation have a lower median survival compared with patients undergoing primary heart/lung transplantation. However, after controlling confounding variables, survival times did not differ significantly between groups. Also, the conditional mean survival of 7.9 years among those who survived to 1 year posttransplant would suggest a survival benefit of heart/lung retransplant. 

Potential Contraindications to Heart/lung Transplant (Applies to All Indications)
Individual transplant centers may differ in their guidelines, and individual patient characteristics may vary within a specific condition. In general, heart transplantation is contraindicated in patients who are not expected to survive the procedure, or in whom patient-oriented outcomes (eg, morbidity, mortality) are not expected to change due to comorbid conditions unaffected by transplantation (eg, imminently terminal cancer, or another disease). Further, consideration is given to conditions in which the necessary immunosuppression would lead to hastened demise (eg, active untreated infection). However, stable chronic infections have not always been shown to reduce life expectancy in heart transplant patients. 

Malignancy 
Pretransplant malignancy is considered a relative contraindication for heart transplantation given that malignancy has the potential to reduce life expectancy and could prohibit immune suppression after transplantation. However, with improved cancer survival and use of cardiotoxic chemotherapy and radiotherapy, the need for heart transplantation has increased in this population.

Mistiaen et al (2015) conducted a systematic review to study the posttransplant outcomes for pretransplant malignancy patients. Most selected studies were small case series (median sample size, 17 patients; range, 7-1117 patients; mean age, 6-52 years).16. Hematologic malignancy and breast cancer were the most common types of pretransplant malignancies. Dilated, congestive, or idiopathic cardiomyopathy were the most common reasons for transplantation in 4 case series, chemotherapy-related cardiomyopathy was the most important reason for transplantation in the other series. Hospital mortality rates ranged between 0% and 33%, with small sample sizes potentially explaining the observed variation. A large series by Oliveira et al (2012) reported similar short- and long-term posttransplant survival rates for chemotherapy-related (n=232) and other nonischemic cardiomyopathy (n=8890) patients.17. The 1-, 3-, and 5-year survival rates were 86%, 79%, and 71% for patients with chemotherapy- related cardiomyopathy compared with 87%, 81%, and 74% for other transplant patients, respectively. Further, 2-, 5-, and 10-year survival rates among pretransplant malignancy patients were found to be comparable with other transplant patients. In addition to the non- malignancy-related factors such as cardiac, pulmonary, and renal dysfunction, 2 malignancy- related factors were identified as independent predictors of 5-year survival. A malignancy-free interval (the interval between treatment of cancer and heart transplantation) of less than 1 year was associated with lower 5-year survival (<60%) than with a longer interval (>75%).

Patients with prior hematologic malignancies had an increased posttransplant mortality in 3 small series. For example, as reported by Sigurdardottir et al (2012) Recurrence of malignancy was more frequent among patients with a shorter disease-free interval: 63%, 26%, and 6% among patients with less than 1 year, 1 to 5 years, and more than 5 years of disease-free interval, respectively.18.

Yoosabai et al (2015) conducted a retrospective review of 23,171 heart transplant recipients in the OPTN/UNOS database to identify whether pretransplant malignancy increased the risk of posttransplant malignancy.19.  Posttransplant malignancy was diagnosed in 2673 (11.5%) recipients during the study period. A history of any pretransplant malignancy was associated with increased risk of overall posttransplant malignancy (subhazard ratio, 1.51; p<0.01), skin malignancies (subhazard ratio, 1.55; p<0.01), and solid organ malignancies (subhazard ratio, 1.54; p<0.01) on multivariate analysis. 

Recurrence Risk 
The evaluation of a candidate who has a history of cancer must consider the prognosis and risk of recurrence from available information including tumor type and stage, response to therapy, and time since therapy was completed. Although evidence is limited, patients in whom cancer is thought to be cured should not be excluded from consideration for transplant. The ISHLT guidelines have recommended stratifying each patient with pretransplant malignancy as to their risk of tumor recurrence and that cardiac transplantation should be considered when tumor recurrence is low based on tumor type, response to therapy, and negative metastatic workup. The guidelines also recommended that the specific amount of time to wait for transplant after neoplasm remission will depend on these factors and no arbitrary time period for observation should be used. 

HIV Infection 
Aguero et al (2016) reported on a review on heart transplantation among HIV-infected patients.20. Since 2001, 12 heart transplantations in patients with HIV infection have been reported and 3 patients acquired HIV after heart transplantation. Fourteen (93%) of these 15 patients were younger than 50 years of age, with cluster of differentiation 4 counts greater than 200 cells/mm3, and all of them were taking antiretroviral therapy. Thirteen were alive with normal graft function at the end of follow-up. One patient had suboptimal adherence to antiretroviral therapy and died of multiorgan failure. The cause of death in the other patient was not reported. There are few data directly comparing outcomes for patients with and without HIV or for combined heart/lung transplants.

Current OPTN policy permits HIV-positive transplant candidates.6.

The British HIV Association and the British Transplantation Society (2017) updated their guidelines on kidney transplantation in patients with HIV disease.21. These criteria may be extrapolated to other organs:

  • Adherent with treatment, particularly antiretroviral therapy
  • Cluster of differentiation 4 count greater than 100 cells/mL (ideally >200 cells/mL) for at least 3 months
  • Undetectable HIV viremia (<50 HIV-1 RNA copies/mL) for at least 6 months
  • No opportunistic infections for at least 6 months
  • No history of progressive multifocal leukoencephalopathy, chronic intestinal cryptosporidiosis, or lymphoma. 

Other Potential Contraindications 
Considerations for heart transplantation and lung transplantation alone may also pertain to combined heart/lung transplantation. For example, cystic fibrosis accounts for most pediatric candidates for heart/lung transplantation, and infection with Burkholderia species is associated with higher mortality in these patients. 

Summary of Evidence 
For individuals who have end-stage cardiac and pulmonary disease who receive combined heart/lung transplant, the evidence includes case series and registry data. Relevant outcomes are overall survival, symptoms, morbid events, and treatment-related morbidity and mortality. The available literature reports on outcomes after heart/lung transplantation. Given the exceedingly poor expected survival rates without transplantation, this evidence is sufficient to demonstrate that heart/lung transplantation provides a survival benefit in appropriately selected patients. Transplant may be the only option for some patients with end-stage cardiopulmonary disease. Heart/lung transplant is contraindicated for patients in whom the procedure is expected to be futile due to comorbid disease or for whom posttransplantation care is expected to worsen comorbid conditions significantly. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome.

For individuals who have a combined heart/lung transplant complicated by graft failure or severe dysfunction of the heart/lung and who receive a combined heart/lung retransplant, the evidence includes case series and registry data. Relevant outcomes are overall survival, symptoms, morbid events, and treatment-related morbidity and mortality. A very limited amount of data has suggested that, after controlling for confounding variables, survival rates after primary and repeat heart/lung transplants are similar. Findings are inconclusive due to the small number of cases of repeat heart/lung transplants reported in the published literature. Repeat heart/lung transplantation is, however, likely to improve outcomes in patients with a prior failed transplant who meet the clinical criteria for heart/lung transplantation. The evidence is sufficient to determine that the technology results in a meaningful improvement in the net health outcome. 

Practice Guidelines and Position Statements 
The International Society for Heart and Lung Transplantation (2014) updated its consensus- based guidelines on the selection of lung transplant recipients.22. These guidelines made the following statements about lung transplantation:

“Lung transplantation should be considered for adults with chronic, end-stage lung disease who meet all the following general criteria:

  • High (>50%) risk of death from lung disease within 2 years if lung transplantation is not performed.
  • High (>80%) likelihood of surviving at least 90 days after lung transplantation.
  • High (>80%) likelihood of 5-year post-transplant survival from a general medical perspective provided that there is adequate graft function.” 

For combined heart/lung transplant, the guidelines have stated that patients with irreversible myocardial dysfunction or irreparable congenital defects in conjunction with intrinsic lung disease or severe pulmonary arterial hypertension are appropriate candidates for heart/lung transplantation. The guidelines also mentioned that isolated bilateral lung transplantation is associated with comparable or better outcomes in most patients with pulmonary hypertension associated with right ventricular failure. 

U.S. Preventive Services Task Force Recommendations 
Not applicable.

Ongoing and Unpublished Clinical Trials 
A search of ClinicalTrials.gov in July 2018 did not identify any ongoing or unpublished trials that would likely influence this review.

References:

  1. Christie JD, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult lung and heart-lung transplant report--2010. J Heart Lung Transplant. Oct 2010;29(10):1104-1118. PMID 20870165
  2. Yusen RD, Edwards LB, Dipchand AI, et al. The Registry of the International Society for Heart and Lung Transplantation: Thirty-third Adult Lung and Heart-Lung Transplant Report- 2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. Oct 2016;35(10):1170-1184. PMID 27772669
  3. Organ Procurement and Transplantation Network (OPTN). View Data Reports. n.d.; https://optn.transplant.hrsa.gov/data/view-data-reports/. Accessed July 16, 2018.
  4. Kalogeropoulos AP, Georgiopoulou VV, Giamouzis G, et al. Utility of the Seattle Heart Failure Model in patients with advanced heart failure. J Am Coll Cardiol. Jan 27 2009;53(4):334-342. PMID 19161882
  5. United Network for Organ Sharing (UNOS). Heart/Lung: Submitting LAS exception requests for candidates diagnosed with PH. 2018; https://transplantpro.org/news/thoracic/submitting-las- exception-requests-for-candidates-diagnosed-with-ph-2/. Accessed July 16, 2018.
  6. Organ Procurement and Transplantation Network (OPTN). Organ Procurement and Transplantation Network Policies. 2018; https://optn.transplant.hrsa.gov/media/1200/optn_policies.pdf. Accessed July 13, 2018.
  7. Spahr JE, West SC. Heart-lung transplantation: pediatric indications and outcomes. J Thorac Dis. Aug 2014;6(8):1129-1137. PMID 25132980
  8. Benden C, Edwards LB, Kucheryavaya AY, et al. The Registry of the International Society for Heart and Lung Transplantation: fifteenth pediatric lung and heart-lung transplantation report- 2012. J Heart Lung Transplant. Oct 2012;31(10):1087-1095. PMID 22975098
  9. Benden C, Goldfarb SB, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: seventeenth official pediatric lung and heart-lung transplantation report--2014; focus theme: retransplantation. J Heart Lung Transplant. Oct 2014;33(10):1025- 1033. PMID 25242126
  10. Hill C, Maxwell B, Boulate D, et al. Heart-lung vs. double-lung transplantation for idiopathic pulmonary arterial hypertension. Clin Transplant. Dec 2015;29(12):1067-1075. PMID 26358537
  11. Jayarajan SN, Taghavi S, Komaroff E, et al. Impact of extracorporeal membrane oxygenation or mechanical ventilation as bridge to combined heart-lung transplantation on short-term and long-term survival. Transplantation. Jan 15 2014;97(1):111-115. PMID 24056630
  12. Goldfarb SB, Levvey BJ, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: Nineteenth Pediatric Lung and Heart-Lung Transplantation Report-2016; Focus Theme: Primary Diagnostic Indications for Transplant. J Heart Lung Transplant. Oct 2016;35(10):1196-1205. PMID 27772671
  13. Keeshan BC, Goldfarb SB, Lin KY, et al. Impact of congenital heart disease on outcomes of pediatric heart-lung transplantation. Pediatr Transplant. Mar 2014;18(2):204-210. PMID 24373099
  14. Yusen RD, Edwards LB, Kucheryavaya AY, et al. The registry of the International Society for Heart and Lung Transplantation: thirty-first adult lung and heart-lung transplant report--2014; focus theme: retransplantation. J Heart Lung Transplant. Oct 2014;33(10):1009-1024. PMID 25242125
  15. Shuhaiber JH, Kim JB, Gibbons RD. Repeat heart-lung transplantation outcome in the United States. J Heart Lung Transplant. Oct 2008;27(10):1122-1127. PMID 18926404
  16. Mistiaen WP. Heart transplantation in patients with previous malignancy. An overview. Acta Cardiol. Apr 2015;70(2):123-130. PMID 26148371
  17. Oliveira GH, Hardaway BW, Kucheryavaya AY, et al. Characteristics and survival of patients with chemotherapy-induced cardiomyopathy undergoing heart transplantation. J Heart Lung Transplant. Aug 2012;31(8):805-810. PMID 22551930
  18. Sigurdardottir V, Bjortuft O, Eiskjaer H, et al. Long-term follow-up of lung and heart transplant recipients with pre-transplant malignancies. J Heart Lung Transplant. Dec 2012;31(12):1276-1280. PMID 23089300
  19. Yoosabai A, Mehta A, Kang W, et al. Pretransplant malignancy as a risk factor for posttransplant malignancy after heart transplantation. Transplantation. Feb 2015;99(2):345-350. PMID 25606783
  20. Aguero F, Castel MA, Cocchi S, et al. An update on heart transplantation in human immunodeficiency virus-infected patients. Am J Transplant. Jan 2016;16(1):21-28. PMID 26523614
  21. Working Party of the British Transplantation Society. Kidney and Pancreas Transplantation in Patients with HIV. Second Edition (Revised). British Transplantation Society Guidelines. Macclesfield, UK: British Transplantation Society; 2017.
  22. Weill D, Benden C, Corris PA, et al. A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. Jan 2015;34(1):1-15. PMID 25085497
  23. Center for Medicare & Medicaid Services (CMS). Decision Memo for TRANSPLANT Centers: Re-Evaluation of Criteria for Medicare Approval (CAG-00061N). 2000; https://www.cms.gov/medicare-coverage-database/details/nca-decision- memo.aspx?NCAId=75&NcaName=Transplant+Centers*3a%24+Re- Evaluation+of+Criteria+for+Medicare+Approval&CoverageSelection=National&KeyWord=transp lant&KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAABAAEAAA&. Accessed July 16, 2018.

Coding Section

Codes Number Description
CPT 33930 Donor cardiectomy-pneumonectomy (including cold preservation)
  33933 Backbench standard preparation of cadaver donor heart/lung allograft prior to transplantation, including dissection of allograft from surrounding soft tissues to prepare aorta, superior vena cava, inferior vena cava, and trachea for implantation
  33935 Heart/lung transplant with recipient cardiectomy-pneumonectomy
  33960-33961 Prolonged extracorporeal circulation code range
ICD-9 Procedure 33.6 Combined heart/lung transplantation
  39.61 Cardiopulmonary bypass
ICD-9 Diagnosis 277.02 Cystic fibrosis with pulmonary manifestations
  416.0 Primary pulmonary hypertension
  416.8 Other chronic pumonary heart diseases (includes pulmonary hypertension, secondary)
  428.1-428.9 Heart failure, code range
  491.20-491.22 Chronic obstructive bronchitis code range (includes COPD)
  492.0-492.8 Emphysema code range
  515 Pulmonary fibrosis
  745.4 Eisenmenger complex or syndrome
HCPCS No code  
ICD-10-CM (effective 10-01-15) E84.0, E84.8-E84.9 Cystic fibrosis code range
  I27.0 Primary pulmonary hypertension
  I27.1-I27.9 Other pulmonary heart diseases (includes Eisenmenger's complex)
  I50.1-I50.9 Heart failure code range
  J43.0-J43.9 Other chronic obstrctive pulmonary disease code range
  J84.1 Other interstitial pulmonary diseases with fibrosis
ICD-10-PCS (effective date 10/01/15) 02YA0Z0 Surgical, heart and great vessels, transplantation, heart, open allogeneic
  0BYK0Z0, 0BYL0Z0, 0BYM0Z0 Surgical, respiratory system, transplantation, open, allogeneic, code by bilateral, left or right lung(s)
Type of Service Surgery  
Place of Service Inpatient  

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive. 

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross and Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

"Current Procedural Terminology© American Medical Association.  All Rights Reserved" 

History From 2013 Forward     

01/17/2019 

Annual review, no change to policy intent. Updating background, rationale and references. 

02/14/2018 

Annual review, no change to policy intent. Updating background, description, rationale and references. 

01/04/2017 

Annual review, no change to policy intent.

01/25/2016 

Annual review, no change to policy intent. Updating background, description, rationale and references. 

01/14/2015 

Annual review, no change to policy intent. Updated background, description, rationale and references. Added coding.

01/14/2014

Annual review. Added related policies, update rationale and references. Correct the outline format in the cardiac specific area of the guidelines. Updated policy verbiage to include verbiage regarding retransplantation and investigational situations.  


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