Heart Transplant

POLICY NUMBER

A.7.03.09

DESCRIPTION

A heart transplant and a retransplant consist of replacing a diseased heart with a healthy donor heart. Transplantation is used for individuals with refractory end-stage cardiac disease.

Solid Organ Transplantation

Solid organ transplantation offers a treatment option for patients with different types of end-stage organ failure that can be lifesaving or provide significant improvements to a patient’s quality of life. Many advances have been made in the last several decades to reduce perioperative complications. Available data supports improvement in long-term survival as well as improved quality of life, particularly for liver, kidney, pancreas, heart, and lung transplants. Allograft rejection remains a key early and late complication risk for any organ transplantation. Transplant recipients require life-long immunosuppression to prevent rejection. Patients are prioritized for transplant by mortality risk and severity of illness criteria developed by Organ Procurement and Transplantation Network and United Network for Organ Sharing.

Heart Transplant

In 2023, 46,632 transplants were performed in the United States procured from more than 39,679 deceased donors and 6,953 living donors. Heart transplants were the third most common procedure with 4,039 transplants performed from both deceased and living donors in 2023. As of June 2024, there were 3,440 patients on the waiting list for a heart transplant. Rose and colleagues reported a 62% lower rate of heart transplants among women compared with men and a 46% lower rate in Black men compared with White men in a retrospective database review from 2010 to 2018.

Most heart transplant recipients now are hospitalized as status 1 patients at the time of transplant. This shift has occurred due to the increasing demand for the scarce resource of donor organs resulting in an increased waiting time for recipients. Patients initially listed as status 2 candidates may deteriorate to a status 1 candidate before a donor organ becomes available. Alternatively, as medical and device therapy for advanced heart failure improves, some patients on the transplant list will recover enough function to be delisted. Lietz and Miller (2007) reported on survival for patients on the heart transplant waiting list, comparing the era between 1990 and 1994 with the era of 2000 to 2005. One-year survival for a United Network for Organ Sharing status 1 candidate improved from 49.5% to 69.0%. Status 2 candidates fared even better, with 89.4% surviving 1 year compared with 81.8% in the earlier time period.

Johnson and colleagues reported on waiting list trends in the United States between 1999 and 2008. The proportion of patients listed as status 1 increased, even as the waiting list and posttransplant mortality for this group have decreased. Meanwhile, status 2 patients have decreased as a proportion of all candidates. Completed transplants have trended toward the extremes of age, with more infants and patients older than age 65 years having transplants in recent years. Bakhtiyar and colleagues (2020) evaluated survival among patients (N=95,323) wait-listed for heart transplantation between January 1, 1987 and December 29, 2017 using UNOS data. Results revealed 1-year survival on the wait list increased from 34.1% in 1987 to 1990 to 67.8% in 2011 to 2017 (difference in proportions, 0.34%; 95% CI, 0.32% to 0.36%; p<.001). One-year wait list survival also significantly increased for candidates with ventricular assist devices from 10.2% in 1996 to 2000 to 70% in 2011 to 2017 (difference in proportions, 0.60%; 95% CI, 0.58% to 0.62%; p<.001).

Alshawabkeh and colleagues reported on the 1-year probability of the combined outcome of death or delisting due to clinical worsening for patients on the heart transplant waiting list, comparing the periods of April 1, 1986 to January 19, 1999, (early era) and January 20, 1999 to June 2, 2014 (current era). For adults without congenital heart disease (CHD), the probability of the combined outcome was lower in the current era compared with the early era, regardless of whether the patient was listed in status I (14.5% vs 22.7%; p<0.0001) or 2 (9.0% vs 12.8%, p<0.0001). When comparing the current and early eras in adults with CHD, a reduction in the probability of the combined outcome was demonstrated in those listed in status I (17.6% vs 43.3%, respectively; p<0.0001), whereas the outcome remained unchanged for those listed in status 2 (10.6% vs 10.4%, respectively; p=.94).

In adults with CHD, factors associated with waitlist death or delisting due to clinical worsening within 1 year were also examined by Alshawabkeh and colleagues. A multivariate analysis identified that an estimated glomerular filtration rate less than 60 ml/min/1.73 m² (hazard ratio [HR], 1.4; 95% confidence interval [CI], 1.0 to 1.9; p=0.043), albumin less than 3.2 g/dl (HR, 2.0; 95% CI, 1.3 to 2.9; p<0.001), and hospitalization at the time of listing in the intensive care unit (HR, 2.3; 95% CI, 1.6 to 3.5; p<0.001) or a non-intensive care hospital unit (HR, 1.9; 95% CI, 1.2 to 3.0; p=0.006) were associated with waitlist death or delisting due to clinical worsening within 1 year.

Magnetta and colleagues reported outcomes for children on the heart transplant waiting list, comparing the periods of December 16, 2011 to March 21, 2016 (era 1) and March 22, 2016 to June 30, 2018 (era 2). There was a significant decrease from era 1 to era 2 in the proportion of patients listed as status 1 (70% vs 56%; p<0.001), while the proportion of patients with CHD significantly increased across eras (49% to 54%; p=0.018). The median time on the waitlist increased from 68 days to 78 days (p=0.005). There were no significant differences across eras in the cumulative incidence of death on the waitlist among all candidates (subdistribution hazard ratio, 0.96; 95% CI, 0.80 to 1.14; p=.63) and among those listed status 1A (subdistribution hazard ratio, 1.16; 95% CI, 0.95 to 1.41; p= .14). Graft survival at 90 days was also similar across eras in the overall population and in those with CHD (p>.53 for both).

As a consequence, aggressive treatment of heart failure has been emphasized in recent guidelines. Prognostic criteria have been investigated to identify patients who have truly exhausted medical therapy and thus are likely to derive the maximum benefit for heart transplantation. Maximal oxygen consumption (VO₂max), which is measured during maximal exercise, is a measure suggested as a critical objective criterion of the functional reserve of the heart. The American College of Cardiology and American Heart Association have adopted VO₂max as a criterion for patient selection.

Methods other than VO₂max have been proposed as predictive models in adults. The Heart Failure Survival Scale and the Seattle Heart Failure Model (SHFM) are examples. In particular, the SHFM provides an estimate of 1-, 2-, and 3-year survival with the use of routinely obtained clinical and laboratory data. Information on pharmacologic and device usage is incorporated into the model, permitting some estimation on the effects of current, more aggressive heart failure treatment strategies. Levy and colleagues introduced the model using a multivariate analysis of data from the Prospective Randomized Amlodipine Survival Evaluation-1 heart failure trial (N=1125). Applied to the data of 5 other heart failure trials, SHFM correlated well with actual survival (r=0.98). SHFM has been validated in both ambulatory and hospitalized heart failure populations, but with a noted underestimation of mortality risk, particularly in Black adults and device recipients. None of these models has been universally adopted by transplant centers.

Solid organ transplants are a surgical procedure and, as such, are not subject to regulation by the U.S. Food and Drug Administration.

The U.S. Food and Drug Administration regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation Title 21, parts 1270 and 1271. Solid organs used for transplantation are subject to these regulations.

Indications for Heart/Lung Transplant are discussed in another policy.

POLICY

No benefits will be provided for a covered transplant procedure unless the Member receives prior authorization through case management from Blue Cross & Blue Shield of Mississippi.

A human heart transplant is considered medically necessary for selected adult and pediatric patients with end-stage heart failure who meet the following criteria below (I) and fall within acceptable guidelines for patient selection below (II), and fall within the highest priority of allocation (III) as indicated below:

I. Patients must meet all of the following criteria:

• Adequate pulmonary, liver, and renal status

• Absence of significant infection that could be exacerbated by immunosuppressive therapy (e.g., chronic active viral hepatitis B, hepatitis C, and human immunodeficiency virus

• Absence of significant systemic disease or condition that could be exacerbated by immunosuppressive therapy after transplant (e.g., systemic lupus erythematosus)

• No history of malignancy within 5 years of transplantation, excluding nonmelanomatous skin cancers

• Documentation of patient compliance with medical management

II. The following indications are to be used as a guideline for patient selection

A. For Adult Individuals: (The American College of Cardiology (ACC) has established the following recipient guidelines for potential adult heart transplant recipients):

• Accepted Indications for Cardiac Transplantation:

1. For hemodynamic compromise due to heart failure demonstrated by any of the following 3 bulleted items,

• Maximal VO₂ (oxygen consumption) <10 mL/kg/min with achievement of anaerobic metabolism;

• Refractory cardiogenic shock;

• Documented dependence on intravenous inotropic support to maintain adequate organ perfusion or

2. Severe ischemia consistently limiting routine activity not amenable to bypass surgery or angioplasty, or

3. Recurrent symptomatic ventricular arrhythmias refractory to ALL accepted therapeutic modalities.

• Probable Indications for Cardiac Transplantation:

1. Maximal VO₂ <14 mL/kg/min and major limitation of the individual's activities, or

2. Recurrent unstable ischemia not amenable to bypass surgery or angioplasty, or

3. Instability of fluid balance/renal function not due to individual noncompliance with regimen of weight monitoring, flexible use of diuretic drugs, and salt restriction.

• Inadequate indications for cardiac transplantation unless other factors as listed above are present:

1. Ejection fraction <20%; 2. History of functional class III or IV symptoms of heart failure; 3. Previous ventricular arrhythmias; 4. Maximal VO₂ >15 mL/kg/min.

B. For Pediatric Individuals: (A 2007 American Heart Association statement lists the following indications for pediatric heart transplantation)

• Individuals with heart failure with persistent symptoms at rest who require one or more of the following:

1. Continuous infusion of intravenous inotropic agents, or

2. Mechanical ventilatory support, or

3. Mechanical circulatory support.

• Individuals with heart disease and symptoms of heart failure who do not meet the above criteria but who have:

1. Severe limitation of exercise and activity (if measurable, such individuals would have a maximum oxygen consumption <50% predicted for age and sex), or

2. Cardiomyopathies or previously repaired or palliated congenital heart disease and significant growth failure attributable to the heart disease, or

3. Near sudden death and/or life-threatening arrhythmias untreatable with medications or an implantable defibrillator, or

4. Restrictive cardiomyopathy with reactive pulmonary hypertension, or

5. Reactive pulmonary hypertension and potential risk of developing fixed, irreversible elevation of pulmonary vascular resistance that could preclude orthotopic heart transplantation in the future, or

6. Anatomic and physiologic conditions likely to worsen the natural history of congenital heart disease in infants with a functional single ventricle, or

7. Anatomic and physiologic conditions that may lead to consideration for heart transplantation without systemic ventricular dysfunction.

Heart retransplantation after a failed primary heart transplant may be considered medically necessary in individuals who meet the criteria for heart transplantation.

Heart transplantation is considered investigational in all other situations.

III. The following indications are to be used as a guideline for priority allocation.

Cardiac-Specific Criteria

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 the United Network for Organ Sharing (UNOS). Donor thoracic organs are prioritized by UNOS on the basis of recipient medical urgency, distance from donor hospital, and pediatric status. Patients who are most severely ill (status 1A) are given the highest priority. Criteria from OPTN for listing status are as follows (Organ Procurement and Transplantation Network, 2015):

A heart transplant should be considered under the members contract transplant benefit.

Coverage is not provided for:

• Services for which the cost is covered/funded by governmental, foundation, or charitable grants

• Organs sold rather than donated to the recipient

POLICY EXCEPTIONS

None

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

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 diseases 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 the ability to adhere to therapy.

Policy-specific potential contraindications:

1. Pulmonary hypertension that is fixed as evidenced by pulmonary vascular resistance (PVR) greater than 5 Wood units, or transpulmonary gradient (TPG) greater than or equal to 16 mm/Hg despite treatment*

2. Severe pulmonary disease, despite optimal medical therapy, not expected to improve with heart transplantation.*

*Some individuals may be candidates for combined heart-lung transplantation (see Heart/Lung Transplant medical policy)

Individuals must meet the United Network for Organ Sharing (UNOS) guidelines for status 1A, 1B, or status 2 (and not currently be Status 7).

A candidate who does not meet the criteria for Status 1A or 1B is listed as Status 2.

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

Cardiac-Specific Criteria

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. Donor thoracic organs are prioritized by UNOS on the basis of recipient medical urgency, distance from donor hospital, and pediatric status. Individuals who are most severely ill (status 1A) are given the highest priority. The following factors are considered in assessing the severity of illness: reliance on continuous mechanical ventilation, infusion of intravenous inotropes, and/or dependency on mechanical circulatory support (ie, total artificial heart, intra-aortic balloon pump, extracorporeal membrane oxygenator, ventricular assist device).

Additional criteria, which are considered in pediatric individuals, include diagnosis of an OPTN-approved congenital heart disease, presence of ductal dependent pulmonary or systemic circulation, and diagnosis of hypertrophic or restrictive cardiomyopathy while less than one year old. Of note, pediatric heart transplant candidates who remain on the waiting list at the time of their 18th birthday without receiving a transplant continue to qualify for medical urgency status based on the pediatric criteria.

Specific criteria for prioritizing donor thoracic organs for retransplant include severe coronary allograft vasculopathy, mild or moderate coronary allograft vasculopathy with a left ventricular ejection fraction less than 45%, coronary allograft vasculopathy with restrictive physiology, or symptomatic graft dysfunction without evidence of active rejection.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B. appropriate with regard to standards of good medical practice; and

C. not solely for the convenience of the Member, his or her Provider; and

D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

8/1998: Approved by Medical Policy Advisory Committee (MPAC).

5/1/2002: Type of Service and Place of Service deleted.

7/21/2005: Review by MPAC: Policy updated; "HIV positivity is not an absolute contraindication to transplant. Each individual transplant center will determine patient selection criteria for HIV positive patients."

10/26/2005: Code Reference section updated: HPCS S2152 added; ICD-9 procedure code 00.93 added, 5th digit added to 37.51; ICD-9 Diagnosis code: 398.0, 422.91, 422.92, 422.93, 425.0, 425.3, 425.4, 428.0, 428.1, 428.22, 428.23, 428.32, 428.33, 428.42, 428.43, 428.9, 429.1, 429.3 added.

3/27/2006: Coding updated. CPT4 2006 revisions added to policy.

12/31/2008: Policy reviewed, prior authorization for evaluation removed.

11/23/2009: Policy Description revised to add link to Heart-Lung Transplantation policy, Policy Statement Section revised to add new medically necessary criteria being patients must now meet specific criteria, fall within patient selection ACC guidelines and priority allocation UNOS guidelines, specific medically necessary criteria added, revised ACC guideline information added, revised UNOS priority allocation information added, non-coverage information added, Coding Section revised to add ICD9 procedure codes 37.99 and 39.61 to Covered Codes Table, ICD9 Diagnosis codes 422.91, 422.92, 422.93 replaced incorrect codes 442.91, 442.93, 442.94 on the Covered Codes Table.

02/24/2012: Contraindications moved to the Policy Guidelines section, and the absolute and relative contraindications were combined. Deleted outdated references from the Sources section.

03/31/2013: Policy reviewed; no changes.

04/24/2014: Added the following policy statements: 1) Heart retransplantation after a failed primary heart transplant may be considered medically necessary in patients who meet criteria for heart transplantation. 2) Heart transplantation is considered investigational in all other situations.

02/19/2015: Policy description updated. Policy statement criteria for pediatric patients regarding anatomical and physiological conditions updated to change "natural history or congenital heart disease" to "natural history of congenital heart disease." In the UNOS priority allocation statement, "donor heart organs" changed to "donor thoracic organs." Added the following statement for Status 1A Adult Patients: If criteria a, b, c, and d are not met, such status can be obtained by application to the applicable Regional Review Board. Revised the statement for Status 1A Pediatric Patients to state that a candidate who does not meet the criteria specified in a, b, c, d, or e may be listed as Status 1A if the candidate has a life expectancy without a heart transplant of less than 14 days, such as due to refractory arrhythmia.

08/25/2015: Code Reference section updated to add ICD-10 codes. Removed ICD-9 procedure codes 37.99 and 39.61.

03/04/2016: Policy description updated regarding 2014 and 2015 data for heart transplants. Policy section updated regarding cardiac-specific criteria for adult and pediatric patients. Policy guidelines section updated to list the policy-specific potential contraindications separately from the potential contraindications subject to the judgment of the transplant center. Added medically necessary and investigative definitions.

06/01/2016: Policy number A.7.03.09 added.

09/29/2017: Code Reference section updated to add new ICD-10 diagnosis codes I50.810, I50.811, I50.812, I50.813, I50.814, I50.82, I50.83, I50.84, and I50.89. Revised description for ICD-10 diagnosis code I50.1. Effective 10/01/2017.

12/05/2017: Policy description updated with new data regarding patients with heart failure. Policy statements unchanged. Policy Guidelines updated to add cardiac-specific criteria.

09/04/2018: Policy description updated regarding new heart transplant data for 2017 and 2018. Added information regarding prioritization of candidates. Policy statements unchanged.

09/13/2019: Policy reviewed; no changes.

09/18/2020: Policy description updated regarding solid organ transplantation and heart transplants. Policy statements unchanged.

12/28/2021: Policy description updated regarding new data for transplants performed in the United States. Policy statements unchanged. Policy Guidelines updated regarding cardiac-specific criteria. Changed "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

11/15/2022: Policy description updated regarding new data for transplants. Policy statements and Policy Guidelines updated to change "patients" to "individuals." Added "cardiac" to policy statements for accepted and inadequate indications for adult individuals.

10/09/2023: Policy description updated regarding new data for transplants. Policy statement updated to change "patient's" to "individual's."

10/23/2024: Policy description updated regarding new data for transplants. Policy statements unchanged.

SOURCE(S)

Blue Cross Blue Shield Association policy #7.03.09

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes

CPT copyright American Medical Association. All rights reserved. CPT is a registered trademark of the American Medical Association.