Heart-Lung Transplantation

Indications

Conceptually, dual organ failure requiring heart-lung transplants may be due to:

• A primary cardiac disease leading to pulmonary failure
• A primary pulmonary disease leading to cardiac failure
• A systemic process causing both cardiac and pulmonary failure [6]

The most common indications (35%) for heart-lung transplants are congenital cardiac malformations causing Eisenmenger syndrome and secondary pulmonary arterial hypertension.[7][8][9] The secondary pulmonary disease becomes unsalvageable when the pulmonary vascular resistance remains greater than 3 to 5 Woods units despite a trial of inotropes and MCS.[8][10] When a heart transplant alone is performed in the face of such high resistance, there is a risk of acute right heart failure.[8]

The second most common group of indications (27%) for heart-lung transplants are primary pulmonary hypertension disorders causing right heart failure.[7][8] The criteria for unsalvageable right heart failure vary between centers, given comparable outcomes between double lung transplant and heart-lung transplant for these patients.[11] Most centers would consider the patient for a heart-lung transplant if cardiomegaly precluded the donor lung from fitting inside the chest or if the right heart is infarcted or fibrotic.[11] Patients with a systemic disease that causes both cardiac and pulmonary failure, such as cystic fibrosis, or with lifestyle factors, such as smoking, which causes both emphysema and ischemic cardiac disease, can be considered for a dual transplant.[8] In the case of cystic fibrosis, the newly explanted recipient heart may be used as a donor organ for another recipient in a so-called “domino” transplant.[3]

Contraindications

Many contraindications for independent lung transplantation and heart transplantation also apply to the combined operation. Active malignancy or a history of malignancy in the last 2 to 5 years is a contraindication to transplant. Active substance use disorder, uncontrolled psychiatric disorders, noncompliance, poor functional status, and poor social support are likewise contraindications to transplant surgery.[11] Blood-type (eg, ABO) incompatibility and a positive crossmatch are contraindications for transplant between a specific donor and recipient. Human leukocyte antigen matching cannot be performed under the ischemic time constraints imposed by current thoracic organ preservation technology. Maximum cold ischemia time for hearts and lungs is described as 4 to 6 hours and 6 to 10 hours, respectively, but the best outcomes are obtained by minimizing all ischemic time.

A large mismatch of donor-recipient lung size is a contraindication to transplant. Although some discrepancy can be tolerated, outside of a range of 10% above or below the recipient’s height or weight, either atelectasis or hyperexpansion pulmonary edema may result.[1][12] Advanced age was previously considered a contraindication to transplant, but the latest pulmonary guidelines now suggest considering the comorbidities and age on a case-by-case basis.[11][13]

A prior history of thoracic surgery was previously considered to be a contraindication to transplant, given the increased risk of blood loss from lysis of pleural and mediastinal adhesions during explantation. However, increasing technical experience and using antifibrinolytic agents have made this consideration obsolete.[11] Classically, serum total bilirubin levels of 2.1 mg/dL or greater were a sign of advanced pulmonary hypertension and early postoperative mortality of 58%.[14] Concomitant liver failure must be approached with caution and may make the patient a candidate for a combined heart-lung-liver transplant.[15]

Preparation

Recipient candidates must undergo an interprofessional care team review and evaluation before being listed for transplant. In the United States, heart-lung transplant recipients are currently listed under the heart allocation system to take advantage of more favorable wait times. The European system has a separate allocation for concomitant heart-lung candidates.[11] The ideal timing of listing a candidate for transplant is a multifactorial decision that varies by the underlying etiology of organ failure.[16]

The local organ procurement organization should adequately evaluate the donor. Donation criteria are occasionally revised to maximize benefits in chronic international donation shortage conditions. There are now standard criteria for lung donors and expanded criteria for lung donors.[17]

Technique or Treatment

There are 3 different operations performed during a heart-lung transplant.[18]  

Donor Procurement

The donor procurement technique varies somewhat between institutions.[19] Generally, after the operating surgeon performs a bronchoscopy confirming adequately healthy airways, the procurement proceeds through a median sternotomy. The pericardium and bilateral pleural spaces are entered, and all anatomy is inspected. The pulmonary ligaments are divided, as are the innominate and azygos veins, allowing for mobilization of the superior and inferior venae cavae, aorta, and proximal trachea. Care is taken not to dissect the distal trachea so as not to jeopardize the blood supply. When all abdominal procurement teams and the thoracic team are ready, IV heparin (approximately 300 U/kg) is administered. Prostaglandin E1 is injected into the main pulmonary artery to combat hypoxic vasoconstriction, and after a brief waiting period, the aorta is cross-clamped.

Cold organ preservation solution is delivered to the heart via an aortic cannula proximal to the aortic clamp and to the lungs via a pulmonary artery cannula. The absence of aortic insufficiency is confirmed to ensure the preservation of the coronary flow solution. The left atrial appendage is amputated and allowed to drain to decompress the heart as ice saline is applied to the organs. After administration of preservation solution, the heart and lung are removed en bloc. The inferior vena cava is divided, leaving enough cuff for the liver team; the superior vena cava is divided with a more generous cuff to avoid damage to the sinoatrial node. The pericardium is separated from the diaphragm. The aorta is divided at the level of the innominate artery. The anesthesia team is asked to pull upward on the endotracheal tube, then mildly inflate the lungs and keep them inflated at low pressure as the trachea is stapled with a thoracoabdominal stapler. Some surgeons will dissect the trachea from the esophagus in the donor's chest; others perform this maneuver on the back table. The organs are then packaged for transport.[1][19]

Recipient Explantation

The recipient explantation (cardiopneumonectomy) proceeds through a median sternotomy, with careful dissection into the pericardium and bilateral pleural spaces, especially in patients with a prior thoracic surgical history. Dissection is often complicated in patients requiring heart-lung transplants, particularly those with Eisenmenger syndrome, on account of their extensive mediastinal venous collaterals. During dissection, avoiding injury to the phrenic, vagus, and recurrent laryngeal nerves is essential. Once dissection is complete, the patient is cannulated through the aorta, superior vena cava, and inferior vena cava and is placed on cardiopulmonary bypass and cooled. The heart is resected, dividing the aorta just distal to the aortic valve and the pulmonary artery to the pulmonic valve. When the right atrium is entered to divide it, some teams will divide at the level of the atrium to leave a cuff of atrial tissue around both the superior and inferior venae cavae; however, other teams will divide at the level of the cava proper, to avoid incorporating arrhythmogenic tissue in the anastomosis.

The left atrium is divided at the level of the atrioventricular groove. After the heart has been removed, the lungs are explained by clamping or stapling each mainstem bronchus and dividing the bronchi and hilar vessels distally. The lungs are then removed en bloc from the chest. The mediastinum can be prepared with the heart and lungs no longer obscuring the field. The remnant pulmonary arteries are excised, except at the ligamentum arteriosum, to provide a buffer for the recurrent laryngeal nerve. The trachea is prepared by dividing it at the level of the right mainstem bronchus. Many centers will implant the new donor hila anterior to the phrenic nerve pedicles for improved mobility to inspect the posterior mediastinum. However, some centers still implant the hila posterior to the phrenic nerve pedicles for improved exposure if reoperation is required. Whichever strategy is chosen, the dissection is completed without phrenic injury, and mediastinal hemostasis is achieved before the donor heart and lungs are implanted and again obscure the exposure.[1]

Recipient Implantation

The recipient implantation procedure begins with preparing the graft on the back table. Nonessential mediastinal tissue is resected, and any atrial defects in the heart are closed. The donor trachea is trimmed to the level of the first or second cartilaginous ring above the carina. Generous saline irrigation and a dedicated suction catheter are used to clear the donor lungs of mucus. When all is ready, the graft is lowered into the recipient's chest and kept cold with periodic cold irrigation or cold gauze pad wrappings.

The anastomoses begin with the trachea; the recipient trachea at the former level of the right mainstem is sutured to the donor trachea at the level 1 or 2 rings above the carina. Some surgeons use only running permanent sutures; others use running sutures on the membranous trachea and interrupted sutures on the cartilaginous trachea. The tracheal anastomosis is covered with nearby tissue, either lymphatic or pericardial, to give a buffer against erosion into the neighboring great vessels.

Once this anastomosis is complete, the chest is irrigated to dilute potential tracheal contamination. Then, attention is turned to the blood vessels. Different surgeons prefer differing orders of anastomoses of the aorta, superior vena cava, and inferior vena cava. The prior left atrial appendage defect created as a vent during donor procurement may be used again as a vent before it is then sutured closed. Once all anastomoses are complete and the circulation is aspirated for air, attention is turned toward meticulous hemostasis. The grafts may need to be gently rotated during hemostasis to achieve adequate exposure. Finally, the patient's anticoagulation is reversed, cardiopulmonary bypass is weaned, chest tubes and pacer wires are placed, the patient's chest is closed, and the patient is brought to recover in the intensive care unit.[1]

Complications

Patients with a heart-lung transplant are at risk for a multitude of early complications, as would be expected after major thoracic transplant surgery. In particular, primary graft dysfunction of the lung from ischemic reperfusion injury results in increasingly severe hypercapnia and hypoxia, with an incidence of 15% to 20% after 48 to 72 hours.[17] Primary cardiac graft failure, defined by severe sustained hemodynamic status without alternative explanation, is another high-risk complication with an incidence of up to 22% and mortality of 53% and seems to be more associated with idiopathic hypertension and sarcoidosis in the recipient.[17] As with any tracheal surgery, the patient is at risk of acute airway emergencies, but this incidence has been reported to be reasonably low, cited to be 3.8% in 1993.[20]

Later complications arise from the transplant conundrum of balancing immune suppression, infections, and medication adverse events against the risk of rejection. Chronic rejection of the lung graft manifested as bronchiolitis obliterans syndrome occurs in 7% and 31% of patients at 1 and 5 years, respectively.[21] Chronic rejection of the heart graft, manifesting as coronary artery vasculopathy, occurs in 8%.[16] 

Immunosuppression protocols and rejection surveillance with echocardiography (with endomyocardial biopsy considered if echocardiography is abnormal), surveillance bronchoscopy with endobronchial biopsy, and spirometry remain center-specific and patient-dependent.[8] Immune suppression must be carefully titrated because, on the other side of the balance, infection in these patients has historically caused 40% of all mortality, with fungal infections being prevalent in the first month and involved in up to 14% of infectious complications.[22] 

Medication-induced adverse events are also common in a high percentage of transplant recipients, eg, 88% with posttransplant hypertension, 70% with hyperlipidemia, 17% to 27% with diabetes, and 46% with renal dysfunction—with 2% to 4% progressing to dialysis.[16][21] These patients must also be monitored for posttransplant malignancies, especially posttransplant lymphoproliferative disorder, which seems to have a higher incidence of 7.6% in those with heart-lung transplant, compared to 5.4% with heart transplant alone and in the lung without heart (3.1%). This complication may occur within the first year.[8] There has been some enthusiastic speculation that multiorgan transplants may have an increased tendency to promote recipient tolerance to the donor organs, in contrast with a single organ transplanted alone. However, this hypothesis does not seem supported in a heart-lung transplant.[21]

Several complications may arise from a complicated surgical dissection. Injury or excess manipulation of the vagus nerves may lead to gastroparesis, gastroesophageal reflux disease, and aspiration. These conditions can be quite adverse to the lung graft and are risk factors for bronchiolitis obliterans syndrome. Injury to the phrenic nerves may result in diaphragmatic paresis manifesting as acute to chronic dyspnea; injury to the thoracic duct may lead to chylothorax.[8]

Clinical Significance

Since the first successful heart-lung transplant in 1981, nearly 4000 patients have been transplanted.[8] With improvements in patient selection and technique, the median survival for heart-lung transplant has been increasing, from 2.1 years (1982-1993) to 3.7 years (1994-2003), to 5.8 years (2004-2016).[21] After the first year postoperatively, survivors can expect a median survival of 10.3 years. One high-volume center (n= 34 over a decade) has reported survival rates of 82%, 69%, 62%, 54%, and 54% at 1, 3, 5, 10, and 15 years, respectively.[16]

This median survival must be seen in the context of patients who are critically ill with dual organ failure, for whom any survival without transplant is virtually unthinkable. Many of these patients are young and would otherwise be in the prime of life; 68% to 78% are younger than 50, and 30% to 35% are between 18 and 34 in North America and Europe, respectively.[21] With improving care for children with congenital cardiac anomalies, survivorship to adulthood is now 75% to 85%. But with longevity comes wear and tear on even the most durable repair of an anomalous circulation; up to 10% to 20% of these patients will still require a transplant in their lifetimes.[16] Heart-lung transplantation provides a valuable extension for quality years of life.[23]

Enhancing Healthcare Team Outcomes

A heart-lung transplant, as a highly complex and life-altering intervention, demands the coordinated efforts of a dynamic, multifaceted team. This team typically includes surgeons, cardiologists, pulmonologists, anesthesiologists, nurses, transplant pharmacists, physical and occupational therapists, respiratory therapists, dietitians, social workers, and clinical psychologists. Each healthcare professional plays a critical role, from preoperative assessments to postoperative care. Effective collaboration and interprofessional communication are crucial to ensuring patient-centered care, minimizing complications, and improving long-term outcomes. For instance, pharmacists ensure proper immunosuppressive therapy, while dietitians and therapists promote recovery and physical function. Social workers and psychologists help address psychosocial, behavioral, and demographic factors, which are increasingly recognized as important for long-term transplant success.[24]

Care coordination among team members is pivotal in navigating the intricate transplant process, where even minor miscommunications can lead to adverse outcomes. Psychosocial, demographic, and behavioral factors are now recognized as significant determinants of long-term survival in transplant recipients.[25] Thus, the team must work closely with patients and their families, offering education and support to ensure adherence to posttransplant care plans and lifestyle modifications. This collaborative approach enhances patient-centered care, improves long-term outcomes, and promotes team performance, ensuring patients receive the highest standard of care throughout their transplant journey.