Treatments

Heart transplant is performed on patients with end-stage heart (cardiac) disease.  This is usually due to the following reasons:

• Complex congenital heart defects that cannot be set right by routine repair surgeries
• Eisenmenger syndrome (i.e., atrioventricular canal defect, transposition of the great vessels, and truncus arteriosus)
• Irreversible right-heart failure secondary to pulmonary hypertension
• Cystic fibrosis and end-stage bronchiectasis with compromised cardiac function.
• Ischemia, or lack of oxygenated blood to the heart (coronary heart disease), leading to heart attack and permanently damaged heart muscle
• Heart valve disease, such as with damage from rheumatic fever
• Infections of heart tissue, especially heart valves or heart muscle
• Untreated, uncontrolled high blood pressure
• Heart muscle disease, secondary to multiple causes
• Certain drugs

Usually lung transplants are performed for

• Chronic obstructive lung diseases such as emphysema
• Cystic fibrosis
• Idiopathic pulmonary fibrosis
• Primary pulmonary hypertension – High pressure in the arteries (of unknown cause) that supply blood to the lungs
• Alpha1 antitrypsin deficiency

Patients having end stage heart and lung diseases are given combined heart and lung transplants.

Contraindications

• The upper age limit is usually 60 years but the physiological age and fitness for surgery is considered
• Other significant cardiovascular disease, such as a stroke, splanchnic or peripheral vascular disease
• Kidney failure
• Mental disabilities
• HIV positive

Symptoms of Heart failure

Most important symptoms of heart failure to watch out for are:

• Shortness of breath – on exertion, but later at rest (Dyspnoea)
• Short of breath when lying flat (Orthopnoea).
• Waking up breathless in the middle of the night, needing to sit or stand upright (Paroxysmal Nocturnal Dyspnoea).

Other symptoms can be:

• Nausea and vomiting
• Weight gain
• Confusion
• Swelling of your arms and legs (oedema)
• Severe fatigue and tiredness
• Decreased urine

Symptoms of Lung Disease

• Coughing, wheezing.
• Severe shortness of breath limiting routine activity
• Dependence on bronchodilators, steroids and oxygen
• Recurrent pneumonias and excessive sputum production
• Fatigue, tiredness
• Cyanosis or bluish discoloration of the skin and lips (due to poor oxygenation)

Pre-operative work-up is extremely important for proper treatment and recovery.

• A team, consisting of a Cardiologist, Pulmonologist, Nephrologist, Infectious diseases specialist and Psychiatrist is involved in the pre-operative planning of the patient’s evaluation and treatment.
• Complete review of medical, surgical, genetic and family history, co-morbidities, medications, lifestyle and environmental exposure
• Full physical examination with particular attention to signs of co-morbidities including gastrointestinal (GI) disturbances, bleeding, vascular insufficiency, and occult cancer.
• Laboratory tests
  • Hepatitis panel, HIV testing, testing for Epstein-Barr virus (EBV), cytomegalovirus (CMV), and herpes simplex virus (HSV)
  • Fungal serologic testing and tuberculin (TB)
  • Prostate-specific antigen (PSA) in males
  • Papanicolaou test in females.
  • Alpha 1-antitrypsin levels
  • Complete blood count (CBC) with differential
  • Platelet count
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT)
  • Complete blood chemistry – liver function tests, lipid profile, urinalysis,
  • Blood typing and screening
  • Panel-reactive antibody (PRA) testing
  • Tissue typing
• Imaging studies
  • Computed tomography (CT) of the thorax, and chest X Rays for thorax size and to rule out other diseases
  • Echocardiography and dynamic magnetic resonance imaging (MRI) – to determine right ventricular ejection fraction (RVEF).
  • Bilateral mammograms in females
• Cardiac and pulmonary evaluation
  • Pulmonary function test results, including diffusion capacity of lung for carbon monoxide (DLCO) and maximal venous oxygen consumption (MVO2)
  • Right- and left-heart catheterization – to determine whether the disease process is reversible or can be treated without transplant.
  • Evaluating the pulmonary vascular resistance – low resistance would indicate heart transplant only is required.
• Biopsy – This is indicated in systemic sarcoidosis

Pre-operative support measures

Clinical condition is maintained optimally with the following:

• Medicines to improve the condition of the heart and lung
• Exercise and weight-loss programs to improve overall condition and help in post-operative recovery
• Psychological counselling to prepare for the peri operative period as well as life after transplant.

In patients with severe cardiac failure, the following support can be used while waiting for a transplant:

• A “bridge” device (assisted device) – a balloon pump is inserted into the aorta and is attached to a battery generator device that can help the heart to provide blood flow to the body. This is very short term support only.
• Implantation of a Left Ventricular Assist Device (LVAD) – a mechanical pump to help pump the blood. This can be used for months or even years.
• Total artificial hearts, (rare and expensive).

Surgery:

A median sternotomy incision (the rib cage is split down the sternum) is made for initial inspection of the heart and lungs. Cardiopulmonary bypass is used.

The heart and lungs are removed, with care taken to preserve the phrenic nerves and to address the bronchial artery circulation so as to prevent postoperative bleeding complications.

Next, the new heart and lungs are inserted. The tracheal anastomosis is performed first. The right atrial anastomosis is performed next, followed by the aortic anastomosis. Care is taken to keep the donor trachea as short as possible because of the limited vascularity of the area.

Complications

Rejection

Cardiac rejection is monitored by serial endomyocardial biopsies. Lung rejection is monitored by radiographic changes in the lung fields, and examination of the cellular content of the Broncho alveolar lavage fluid.

Even if there is a suspicion of rejection, anti rejection treatment with steroid pulses (methylprednisolone 500-1000 mg/day for 3-5 days), monoclonal antibody treatment, or polyclonal antibody therapy is instituted.

Implantation response

This is a transient and reversible deterioration in compliance, gas exchange, and pulmonary vascular resistance that occurs immediately after the operation and can last for a week.  This is attributed to lymphatic disruption, ischemia-reperfusion injury, denervation, surgical trauma, fluid overload, and inadequate preservation.

Infection

Cytomegalovirus (CMV) infection – This may be a reactivation of recipient disease caused by the immunosuppression or a de novo infection arising from donor tissue, transfused blood, or other sources. The process proceeds rapidly to respiratory failure and death if aggressive treatment is not initiated. For prophylaxis, patients are generally started on ganciclovir 5 mg/kg/day; for treatment, the same drug and dosage are used.

Other viral, fungal, and bacterial infections can occur, depending on exposure and diagnosis and treatment should be immediate.

Early mobilization of the patient and aggressive chest physiotherapy and treatment can help prevent this complication.  Bacteriologic culture of the donor and recipient trachea may demonstrate potential pathogens and guide appropriate prophylaxis. Diagnosis is confirmed by taking a careful history of the patient’s exposure and by obtaining a Broncho alveolar lavage specimen for culture.

Allograft vascular disease and bronchiolitis obliterans

A concentric myointimal hyperplasia develops in the coronary arteries, and squamous metaplasia and fibrous replacement of the bronchioles in the lungs and is the main causes of late graft failure and death.

Retransplantation is the only treatment.

Patient Education and Consent

A careful medical and psychosocial evaluation of the candidate is mandatory and the family is also involved in this process.

A written contract is negotiated between the transplant center and the patient, with the stipulation that noncompliance with the guidelines is grounds for removal from the program. Both patient and treating doctor must agree to these stipulations.

Patients are instructed to monitor temperature, blood pressure, and pulse oximetry after the procedure and to be alert for symptoms of rejection (which are carefully discussed with the treating doctor). At the first sign of an alteration in their usual state of health, they are to call the transplant centre. Patients are educated in detail about the immunosuppressive medications, their actions, and adverse effects.

Because heart-lung transplant patients are at risk for infection caused by their immunosuppressed state, patients should avoid being in crowds, and wear a mask, and avoid chemical sprays, noxious conditions, fires, and smoke.

Dietary discipline and modifications, viz  low-sodium, low cholesterol diet, are taught to balance the adverse effects of immunosuppressant drugs.

Routine graded exercise is encouraged to maintain muscle tone.

Post surgery rehabilitation is instituted early to assist the patient in regaining normal functional status and good general health.

Monitoring and Follow-up

• Postoperative endomyocardial biopsies are performed at weekly intervals for up to a month to monitor rejection
• Chest X Rays and spirograms are done to check for rejection or infection.  If the imaging shows signs, then bronchoalveolar lavage with transbronchial biopsy is performed.
• Routine outpatient follow-up care is needed at least thrice a week after discharge, to monitor immunosuppression and infection
• Long-term out patient follow-up is done every 3 months, and the following screening tests are performed:
  • Routine tests – electrolytes, cholesterol, glucose, and liver functions, and immunosuppressant drug levels
  • Pulse oximetry and spirometry
  • Cardiac evaluations – echocardiography

Care at home

Both the patient and the family should work together to ensure that post operative rehabilitation is successful.

• Patient can return to work once the treating team gives the go ahead which is usually after 3 to 6 months.
• Proper dental care is a must to prevent dental sepsis leading to systemic infection
• Regular exercise
• Dietary modifications
• To look out for symptoms/ signs of sepsis or rejection
  • Opening of surgical incision; Fluid, blood, or pus leaks from the incision.
  • Fever, sudden weight gain, increase in blood pressure.
  • Shortness of breath, a persistent cough, or sputum.

Post-transplant Medicines

A triple therapy of anti rejection drugs is used – Tacrolimus, Steroids and Azathioprine.

• Tacrolimus – This is used immediately after the transplant.  Common side effects include tremor, high blood pressure, and kidney damage. Other minor side effects include excessive hair loss, high blood pressure, and diabetes. These side effects are usually related to the dose and can often be reversed with proper dosing.
• Corticosteroids – This is used at high doses initially after the transplant and if rejection is detected. Side effects, including easy bruising of the skin, osteoporosis, damage or death of portions of bone, high blood pressure, high blood sugar or diabetes, stomach ulcers, weight gain, acne, mood swings, and a “moon” face.
• Azathioprine – Used for long-term maintenance of immunosuppression. The most common side effects of this drug are suppression of bone marrow functions, such as making blood cells, and liver damage. Many transplant centers are now using a newer drug called mycophenolate mofetil instead of azathioprine.
• Other drugs include cyclosporine, sirolimus, and mizoribine and may have lesser side effects.

Prognosis

• With advances in surgical techniques and immune-suppressing drugs, more than 80% of heart recipients survive more than 3 years after the operation.
• Lung transplantation is a relatively new procedure that continues to be improved. Currently, more than 65% of lung recipients survive at least 3 years after a transplant.