Heart-Lung Transplantation

Number: 0597

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

---

Policy

Scope of Policy

This Clinical Policy Bulletin addresses heart-lung transplantation.

1. Medical Necessity

   Aetna considers heart-lung transplantation medically necessary for persons with severe refractory heart failure plus either end-stage lung disease or irreversible pulmonary hypertension, when the selection criteria listed in section I.B. below are met and no absolute contraindications listed in section I.C. below are present.

   1. Examples of qualifying conditions include the following:

      1. Chronic obstructive pulmonary disease with severe heart failureFootnotes*
      2. Congenital heart disease associated with pulmonary hypertension that are not amenable to lung transplantation and repair by standard cardiac surgery
      3. Cystic fibrosis with severe heart failureFootnotes*
      4. Eisenmenger’s complex with irreversible pulmonary hypertension and severe heart failureFootnotes*
      5. Irreversible primary pulmonary hypertension with severe heart failureFootnotes*
      6. Connective tissue disease or other causes of severe pulmonary fibrosis with uncontrollable pulmonary hypertension or severe heart failureFootnotes*
      7. Severe coronary artery disease or cardiomyopathy with irreversible pulmonary hypertension.

      Footnotes* Severe (New York Heart Association (NYHA) classification III or IV - see Appendix) heart failure where right ventricular function would not be restored with lung transplant alone. Note: Heart-lung transplantation is considered not medically necessary where lung transplantation alone will restore right ventricular function; every attempt should be made to preserve the heart.

      Note: Heart-lung transplantation may be considered medically necessary for other congenital cardiopulmonary anomalies upon individual case review.

   2. Selection Criteria

      The member must meet the transplanting institution’s selection criteria. In the absence of an institution's selection criteria, Aetna considers heart-lung transplantation medically necessary when all of the criteria below are met:

      1. Absence of chronic high-dose steroid therapy. Due to problems in bronchial healing, persons receiving high-dose steroids are considered inappropriate candidates; and
      2. Absence of acute or chronic active infections that are not effectively treated; and
      3. Absence of malignancy (other than non-melanomatous skin cancers or low-grade prostate cancer) or malignancy has been completely resected or (upon medical review) it is determined that malignancy has been treated with small likelihood of recurrence and acceptable future risks; and
      4. Adequate functional status.  Active rehabilitation is considered important to the success of transplantation. Under established guidelines, mechanically ventilated or otherwise immobile persons are considered poor candidates for transplantation; however, bridge to transplant with ambulatory ECMO does not, in itself, rule out candidacy for heart-lung transplantation; and
      5. Adequate liver and kidney function, defined as a bilirubin of less than 2.5 mg/dL and a glomerular filtration rate (GFR) greater than 40 mL/min/1.73 m²; and
      6. Life expectancy (in the absence of cardiopulmonary disease) of greater than 2 years; and
      7. No active alcohol or chemical dependency that interferes with compliance to a strict treatment regimen; and
      8. No uncontrolled and/or untreated psychiatric disorders that interfere with compliance to a strict treatment regimen; and
      9. HIV/AIDS, if present, is under adequate control, defined as:
         
         
         1. CD4 count greater than 200 cells/mm³ for more than 6 months; and
         2. HIV-1 RNA (viral load) undetectable; and
         3. On stable anti-viral therapy more than 3 months; and
         4. No other complications from AIDS, such as opportunistic infections (e.g., aspergillus, tuberculosis, Pneumocystis carinii pneumonia, toxoplasmosis encephalitis, cryptococcal meningitis, disseminated coccidioidomycosis, other resistant fungal infections) or neoplasms (e.g., Kaposi's sarcoma, non-Hodgkin’s lymphoma).

   3. Contraindications

      Heart-lung transplant is considered not medically necessary for persons with any of the following contraindications because the risks of transplantation exceed the benefits:

      1. Gastrointestinal disease (e.g., bleeding peptic ulcer, diverticulitis, chronic hepatitis, active or recurrent pancreatitis);
      2. Multi-system disease - persons with potentially multi-system diseases such as systemic sclerosis (scleroderma) or other collagen vascular diseases such as systemic lupus erythematosus must be carefully evaluated to ensure that their disease is primarily confined to the lung; persons with diabetes must be carefully evaluated to rule out significant diabetic complications such as nephropathy, neuropathy or retinopathy;
      3. Other effective medical treatments or surgical options are available;
      4. Progressive neuromuscular disease;
      5. Refractory uncontrolled hypertension;
      6. Severe musculoskeletal disease with debilitating thoracic involvement;
      7. Smoking - persons with a history of smoking must be abstinent for at least 3 months before being considered a candidate for lung transplant;
      8. Untreated or unstable cerebrovascular disease.

2. Related Policies

   1. CPB 0546 - Extracorporeal Membrane Oxygenation (ECMO)
   2. CPB 0586 - Heart Transplantation
   3. CPB 0598 - Lung Transplantation
   4. CPB 0654 - Ventricular Assist Devices

---

Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes covered if selection criteria are met:
33930 - 33945	Heart/lung transplant
HCPCS codes covered if selection criteria are met:
S2054	Transplantation of multivisceral organs
S2055	Harvesting of donor multivisceral organs, with preparation and maintenance of allografts; from cadaver donor
S2060	Lobar lung transplantation
S2061	Donor lobectomy (lung) for transplantation, living donor
ICD-10 codes covered if selection criteria are met:
E84.0 - E84.9	Cystic fibrosis
I25.10 - I25.9	Chronic ischemic heart disease
I26.01 - I127.9	Pulmonary heart disease
I42.0 - I43	Cardiomyopathy
I50.1 - I50.9	Heart failure
J40 - J47.9	Chronic lower respiratory diseases
J84.10	Pulmonary fibrosis, unspecified
J84.89	Other specified interstitial pulmonary diseases
M32.0 - M35.9	Diffuse diseases of connective tissue
Q20.0 - Q28.9	Congenital malformations of the circulatory system
T86.20 - T86.298	Complications of heart transplant
T86.30 - T86.19	Complications of heart-lung transplant
T86.810 - T86.819	Complications of lung transplant

---

Background

Combined heart–lung transplantation (HLTx) is an established but infrequently performed therapeutic option reserved for carefully selected individuals with end-stage, irreversible cardiopulmonary failure in whom isolated heart or lung transplantation would not provide adequate physiologic benefit (Le Pavec et al. 2018). The procedure is most commonly indicated for complex congenital heart disease with Eisenmenger physiology and advanced pulmonary vascular disease with associated cardiac dysfunction (Arvanitaki et al. 2022; Humbert et al. 2023). Advances in bilateral lung transplantation, pulmonary arterial hypertension–targeted therapies, and mechanical circulatory support have substantially narrowed the indications for HLTx, resulting in low procedural volumes worldwide (Le Pavec et al. 2018). Contemporary data demonstrate improving outcomes over time; however, early post-transplant mortality may be higher than with isolated thoracic organ transplantation in some analyses, while intermediate- and long-term survival appear comparable in selected populations (Yan et al. 2023). Literature support the role of HLTx as a life-prolonging intervention in highly selected candidates (Shin et al., 2022; Treffalls et al., 2024).

Reduced cardiac output and edema characterize patients with heart failure, while patients with respiratory failure exhibit abnormalities in oxygenation and carbon dioxide elimination that impair the functioning of vital organs. These patients have a lower life expectancy and decreased quality of life. Since its introduction at Stanford University in 1981 and at Pittsburgh University in 1982 for the treatment of Eisenmenger's syndrome and terminal pulmonary vascular disease, heart-lung transplantation has become a successful therapeutic option for patients with end-stage cardiopulmonary disease. Heart-lung transplantation is most frequently performed for patients with congenital heart disease (about 30%), primary pulmonary hypertension (about 27%), cystic fibrosis (about 16%), miscellaneous conditions (about 15%), lung emphysema (about 4%), re-transplantation following a failed primary transplant (about 3%), idiopathic pulmonary fibrosis (about 3%), and alpha-1-antitrypsin deficiency (about 2%).

Adults who have undergone heart-lung transplantation for congenital heart disease are expected to have survival rates comparable to those of adults without congenital heart disease. Furthermore, heart-lung transplantation results in survival rates comparable to those reported for single- or double-lung transplantation for patients with primary pulmonary hypertension. Obliterative bronchiolitis, a form of chronic rejection, is a significant cause of late death.

The frequency of heart-lung transplantation is partly limited by the number of available donor organs. There are fewer donor heart-lung preparations than donor heart preparations alone because brain death may be associated with neurogenic pulmonary edema. In addition, aspiration into the lung is common during the course of severe trauma and resuscitation. Prolonged ventilatory support may also predispose the potential donor to nosocomial infection, and direct thoracic trauma may result in pulmonary contusion. As a consequence, probably less than 20% of potential heart donors have lungs that are suitable for heart-lung transplantation. It should be noted that heart-lung transplantation, in some ways, is a technically easier procedure than heart transplantation since the former requires only right atrial, aortic, and tracheal anastomoses, thus avoiding several of the anastomoses associated with heart transplantation.

Contraindications to heart-lung transplantation include irreversible end-organ diseases (e.g., renal, hepatic), active malignancy or infections, systemic diseases (e.g., autoimmune, vascular, amyloidosis), chronic gastrointestinal disease (e.g., diverticulitis, active or recurrent pancreatitis, bleeding peptic ulcer), psychiatric disorders, cerebrovascular disease, progressive neuromuscular disease, and the use of tobacco products. Under established guidelines, obese patients (greater than 20% of ideal body weight), cachectic patients (less than 80% of ideal body weight), mechanically ventilated, or otherwise immobile patients are considered poor candidates for transplantation.

Early postoperative complications (within the first postoperative month) comprise acute isolated lung rejection, multi-organ failure, and bacterial pneumonia. Late postoperative complications (after 1 postoperative month) comprise viral pneumonia, fungal infection, tuberculosis, and chronic obliterative bronchiolitis.

Zheng et al. (2011) examined the safety and possible benefits of laparoscopic anti-reflux surgery in pediatric patients following lung and heart-lung transplantation. An Institutional Review Board-approved retrospective chart review was performed to evaluate the outcomes and complications of laparoscopic anti-reflux surgery in pediatric lung and heart-lung transplant patients. Spirometry data were collected for bronchiolitis obliterans syndrome (BOS) staging using BOS criteria for children. A total of 25 lung and heart-lung transplants were performed between January 2003 and July 2009. Eleven transplant recipients, including 6 double-lung and 5 heart-lung, with a median age of 11.7 years (range of 5.1 to 18.4 years), underwent a total of 12 laparoscopic Nissen fundoplications at a median of 427 days after transplant (range of 51 to 2310 days). The diagnosis of gastroesophageal reflux disease (GERD) was made based on clinical impression, pH probe study, gastric emptying study, and/or esophagram in all patients. Three patients already had a gastrostomy tube in place, and 2 had one placed at the time of fundoplication. There were no conversions to open surgery, 30-day readmissions, or 30-day mortalities. Complications included 1 exploratory laparoscopy for free air 6 days after laparoscopic Nissen fundoplication for a gastric perforation that had spontaneously sealed. Another patient required a revision laparoscopic Nissen 822 days following the initial fundoplication for a para-esophageal hernia and recurrent GERD. The average length of hospital stay was 4.4 ± 1.7 days. Nine of the 12 fundoplications were performed in patients with baseline spirometry values prior to fundoplication and who could also complete spirometry reliably. One of these 9 operations was associated with improvement in BOS stage 6 months after fundoplication; 7 were associated with no change in BOS stage; and 1 was associated with a decline in BOS stage. The authors concluded that it is feasible to perform laparoscopic Nissen fundoplication in pediatric lung and heart-lung transplant recipients without mortality or significant morbidity for the treatment of GERD. The real effect on pulmonary function cannot be assessed due to the small sample size and lack of reproducible spirometry in the younger patients. The authors stated that additional studies are needed to elucidate the relationship between anti-reflux surgery and the potential for improving pulmonary allograft function and survival in children, as has been previously observed in adult patients.

Olland et al. (2013) reviewed evidence comparing heart–lung transplantation (HLTx) and bilateral-lung transplantation (BLTx) for patients with pulmonary hypertension. The review used a structured best evidence topic protocol and evaluated 9 studies selected from 77 identified articles addressing survival, functional outcomes, and procedure selection across heterogeneous pulmonary hypertension populations including idiopathic pulmonary arterial hypertension and Eisenmenger’s syndrome. Across registry data, 1189 (67%) lung transplantations and 578 (33%) HLTx procedures were reported for idiopathic pulmonary hypertension, while HLTx accounted for up to 70% of transplant procedures in Eisenmenger’s syndrome. Reported survival outcomes showed no overall difference between BLTx and HLTx; registry data indicated BLTx half-life survival of 6.8 years and conditional half-life 9.3 years versus HLTx half-life 5 years and conditional half-life 12 years, with idiopathic pulmonary arterial hypertension subsets showing half-life survival of 4.9 years for lung transplantation and 5 years for HLTx. Individual studies reported no difference in overall survival (P = 0.46) and no difference in waiting time (HLTx 8.7 ± 11.8 vs BLTx 6.7 ± 7.5 months; P = 0.2), while perioperative outcomes included higher primary graft dysfunction in BLTx and lower mechanical ventilation duration (P = 0.02) and bronchial complications (P < 0.001) in HLTx. In Eisenmenger’s syndrome, HLTx demonstrated higher survival compared with lung transplantation (P = 0.002) and improved survival in ventricular septal defect patients (P = 0.0001), with increased mortality risk when treated with lung transplantation (relative risk 1.817; P = 0.035). Selection criteria for HLTx included severe right or left heart dysfunction, cardiac index <2.2 l/min/m², congenital heart disease, or chronic inotropic dependence, with reported cut-off ranges of 10–25% for right ventricular ejection fraction and 32–55% for left ventricular ejection fraction. The review concluded that there is no overall survival advantage between HLTx and bilateral lung transplantation (BLTx), as both are safe but suited to different patient subgroups. HLTx is preferred for patients with congenital heart disease, Eisenmenger’s syndrome, or severe right or left ventricular dysfunction (with decision-making informed by approximate RVEF ranges of 10–25% and LVEF ranges of 32–55%), while BLTx offers comparable outcomes for other patients and allows better organ allocation.

Domino Heart Transplant Following Heart-Lung Transplantation

Maynes and colleagues (2020) stated that the domino-donor operation occurs when a "conditioned" heart from the heart-lung transplantation (HLTx) recipient is transplanted into a separate heart transplant (HT) recipient. In a systematic review, these investigators examined the indications and outcomes associated with the domino procedure. They conducted an electronic search to identify all prospective and retrospective studies on the domino procedure in the English literature. A total of 8 studies reported on 183 HLTx recipients and 263 HT recipients who were included in the final analysis. Indications for HLTx included cystic fibrosis in 58% (95% confidence interval [CI]: 27 to 84%) of recipients, primary pulmonary hypertension (PPH) in 17% (95% CI: 12 to 24%), bronchiectasis in 5% (95% CI: 3 to 10%), emphysema in 5% (95% CI: 0 to 45%), and Eisenmenger's syndrome in 4% (95% CI: 2 to 8%). Indications for HT included ischemic heart disease in 40% (95% CI: 33 to 47%), non-ischemic disease in 39% (95% CI: 25 to 56%), and re-transplantation in 10% (95% CI: 1 to 59%). The pooled mean pulmonary vascular resistance (PVR) in HT recipients was 3.05 Woods units (95% CI: 0.14 to 5.95). The overall mortality in the HLTx group was 28% (95% CI: 18 to 41%) at an average follow-up of 15.68 months (95% CI: 0.82 to 30.54), and 35% (95% CI: 17 to 58%) in the HT group at an average follow-up of 37.26 months (95% CI: 6.68 to 67.84). Freedom from rejection in HT was 94% (95% CI: 75 to 99%) at 1 month, 77% (95% CI: 30 to 96%) at 6 months, and 41% (95% CI: 33 to 50%) at 1 year. The authors concluded that the domino procedure appeared to be a viable option in properly selected patients that can be performed safely with acceptable outcomes.

The authors stated that in their GRADE assessment of the level of evidence, they found that the outcomes were of moderate quality, mostly due to the risk of bias associated with retrospective studies. However, since the confidence intervals (CIs) were relatively narrow for most of the variables assessed, this may have increased the quality of evidence to a higher level. Moreover, they noted that this review had several main drawbacks and must be interpreted with care. Differences existed in patient selection, and there was a relative paucity of literature published on this topic. They were unable to perform a quantitative comparison of HLTx versus HT rejection rates since many of the studies analyzed did not have comparative arms for statistical analysis. Differences were also noted among the studies in terms of patient and donor selection, study design, center experiences, immunosuppressive regimens used, techniques, and clinical management of transplant patients. The authors acknowledged that this heterogeneity in the study population was a fundamental drawback that could not be addressed due to the inability to extract sufficient detail from the pooled data.

Double-Lung Versus Heart-Lung Transplantation for End-Stage Cardiopulmonary Disease

Yan et al. (2023) compared post-transplant outcomes following double-lung transplantation (DLTx) and HLTx, based on a search of PubMed, Cochrane Library, and Embase, from inception to March 8, 2022, for studies that report outcomes of these procedures. These researchers then carried out a meta-analysis of baseline characteristics and post-transplant outcomes. Subgroup analyses were performed according to indication, publication year, and center. A total of 10 studies were included in this meta-analysis, involving 1,230 DLTx patients and 1,022 HLTx patients. The DLTx group was characterized by older donors (p = 0.04) and a longer allograft ischemia time (p < 0.001) than the HLTx group. The 2 groups had comparable 1-year, 3-year, 5-year, 10-year survival rates (all p > 0.05), with similar results identified in subgroup analyses. They found no significant differences in 1-year, 5-year, and 10-year chronic lung allograft dysfunction (CLAD)-free survival, length of intensive care unit (ICU) and hospital stay, length of post-operative ventilation, in-hospital mortality, or surgical complications between the groups (all p > 0.05). The authors concluded that DLTx provided similar post-transplant survival to HLTx for end-stage cardiopulmonary disease. These 2 procedures exhibited a comparable risk of CLAD and other post-transplant outcomes.

---

Appendix

The New York Heart Association (NYHA) classification of heart failure is one of the many parameters used for selecting heart-lung recipient. It is a 4-tier system that categorizes individuals based on subjective impression of the degree of functional compromise:

Table: Four NYHA functional classes

Class	Description
Class I	Patients with cardiac disease but without resulting limitation of physical activity.  Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain.  Symptoms only occur on severe exertion.
Class II	Patients with cardiac disease resulting in slight limitation of physical activity.  They are comfortable at rest.  Ordinary physical activity (e.g., moderate physical exertion such as carrying shopping bags up several flights or stairs) results in fatigue, palpitation, dyspnea, or anginal pain.
Class III	Patients with cardiac disease resulting in marked limitation of physical activity.  They are comfortable at rest.  Less than ordinary activity (i.e., mild exertion) causes fatigue, palpitation, dyspnea, or anginal pain.
Class IV	Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort.  Symptoms of cardiac insufficiency or of the anginal syndrome may be present even at rest.  If any physical activity is undertaken, discomfort is increased.

Source: Heidenreich et al. (2022)

---

References