Heart transplantHeart transplant
Heart transplantation has become an established method of treatment of terminal heart failure. The candidates for a heart transplantation are patients for whom conservative therapy has proved to be ineffective, and other surgical methods of the correction of a heart disease do not show good results due to the failure of myocardial function.
The key points at the heart transplantation are the evaluation and selection of recipients, postoperative management, and immunosuppression therapy. Consistent implementation of these steps, in accordance with the protocols of the heart transplantation is the success of the operation.
Pathophysiology of a heart transplant
The pathophysiological changes in the heart in patients who require a heart transplant depends on the cause of the disease. Chronic ischemia causes damage to cardiomyocytes. At the same time a progressive increase in the size of cardiomyocytes, their necrosis and scarring develops. The pathophysiological process of coronary heart disease can affectedby a matched therapy (cardioprotective, antiplatelet, lipid-lowering), by performing coronary artery bypass surgery and angioplasty with stenting. In this case, we can delay the progressive loss of cardiac muscle tissue. There are also cases of distal coronary lesions; in these cases the surgical treatment is ineffective, the function of the heart muscle is gradually reduced, and the heart cavity expands.
The pathological process underlying dilated cardiomyopathy has not yet been studied. Apparently, the deterioration of the mechanical function of the myocardium is affected by an increase in cardiomyocytes, the expansion of the cavities of the heart and the depletion of energy.
The pathophysiological changes in the transplanted heart have their own peculiarities. Denervation of the heart at transplantation leads to the fact that the heart rate is regulated only by humoral factors. As a result of the reduced innervation, myocardial hypertrophy develops. Right heart function in the postoperative period depends on the time of graft ischemia (from clamping of the aorta during donor organ recuperation to the reimplantation and reperfusion) and the adequacy of protection (perfusion preservative solution, the temperature in the container). The right ventricle is very sensitive to the damaging factors and in the early postoperative period may be passive and may not perform any work. Its function can be restored within a few days.
Pathophysiological changes include the processes of rejection: cellular and humoral rejection. Cellular rejection is characterized by perivascular lymphocytic infiltration, and, in the absence of treatment, is followed by the defeat and myocyte necrosis. Humoral rejection is much more difficult to describe and diagnose. It is believed that humoral rejection is mediated by antibodies, which are deposited in the myocardium and cause cardiac dysfunction. The diagnosis of humoral rejection, mainly clinical, is a diagnosis of exclusion, as endomyocardial biopsy in these cases is uninformative.
The late process, peculiar to cardiac allografts, is atherosclerosis of the coronary arteries. The process is characterized by intimal hyperplasia and smooth muscle of small and medium-sized vessels, and is of a diffuse type. The reasons for this phenomenon often remain unknown, but it is believed that cytomegalovirus infection (CMV) infection and graft rejectionmay play their roles. It is believed that this process depends on the growth-factor in allograft circulating lymphocytes. Currently, there is no treatment of this conditio apart from re-transplantation of the heart.
The clinical picture
Candidates for a heart transplant are the patients with heart failure NYHA Class III-IV.
In order to determine the selection of the treatment tactics, functional evaluation of heart failure is often carried out based on the system of the New York Heart Association (NYHA). This system considers the symptoms according to the level of activity and the quality of life of patients.
The New York Heart Association (NYHA) Functional Classification of Heart Failure
No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath).
Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath).
Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea.
Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases.
The general indication for a heart transplant is a marked reduction in heart function, in which the prognosis of survival for one year is unfavorable.
The specific indications for and conditions of heart transplant
• Dilated cardiomyopathy
• Ischemic Cardiomyopathy
• Congenital heart disease after failure or absence of effective treatment (conservative or surgical)
• ejection fraction less than 20%
• intractable angina or malignant arrhythmia after the failure of other treatment
• pulmonary vascular resistance less than 2 Wood units (calculated as (PAWP-CVP) / MW, where PAWP - pulmonary artery wedge pressure, mm Hg .; CVP - central venous pressure, mm Hg .; SV - cardiac output, l / min)
• Age less than 65 years old
• The desire and ability to follow a plan for further treatment and observation
• Age is older than 65 years old; It is a relative contraindication, and patients older than 65 years are estimated individually
• Sustained pulmonary hypertension with pulmonary vascular resistance of more than 4 Wood units
• Active systemic infection
• Active systemic disease, for example, collagen
• Active malignancy; patients with a predicted survival rate of more than 3 or 5 years can be considered candidates; You should also consider the type of tumor
• Smoking, alcohol abuse, drugs
• Psychosocial instability
• Unwillingness or inability to follow the plan fof urther therapeutic and diagnostic measures
Performed clinical tests: complete blood test with platelet count and formula, urine analysis, biochemical blood assay (enzymes, bilirubin, lipid profile, indicators of nitrogen metabolism), coagulation. The research results must be within normal limits. Pathological changes must be specified and, if possible, corrected.
Blood type, the panel of reactive antibodies are determined, tissue typing is performed. These analyzes form the basis of immunologic matching between a donor and a recipient. Also a cross test with donor lymphocytes and the serum of the recipient (cross-match) (determination of anti-HLA-antibodies) is carried out.
Screening for hepatitis B, C. For the carriers of the disease, and in patients with an active process a heart transplant, as a rule, is not indicated (it is a relative contraindication). In various centers around the world the hepatitis in recipients is treated differently; no consensus on this issue has been reached as of now.
Testing for HIV
Positive HIV test is considered a contraindication for heart transplantation.
Epstein-Barr virus, cytomegalovirus, herpes simplex virus. The exposure to these viruses in the past is analysed (IgG) as well as the presence / absence of an active process (IgM). The presence of infection by these viruses indicates an increased risk of reactivation of the disease. After heart transplantation an appropriate preventive antiviral treatment in such patients is required.
It should be noted that when preparing a patient for a heart transplantation (i.e., during the observation and the inclusion in the waiting list) active infectious diseases must be treated. Patients with a negative test for cytomegalovirus infection are usually prescribed with cytomegalovirus immunoglobulin (Tsitogam). During the monitoring period before transplantation in the United States it is recommended to immunise patients with negative tests for IgG to other viral agents.
Tuberculin skin test
Patients with a positive test require a further evaluation and treatment before being included in the waiting list for a heart transplant.
Serology for fungal infections
Serology for fungal infections also helps predict increased risk of the reactivation process after the surgery.
Screening for cancer
Screening for cancer is performed before inclusion in the waiting list.
The study of prostate-specific antigen (PSA)
The study of prostate-specific antigen (PSA). If the result of the analysis is positive, then an appropriate assessment and treatment is required.
Women should undergo a mammogram. The condition for being included in the waiting list is the absence of the disease on the mammogram. In the presence of pathological formations, screening for cancer should be performed as well as all the neccesary treatment before the inclusion in the waiting list.
The condition for inclusion in the waiting list is the absence of pathological changes. In the presence of a pathology, before adding to the waiting list, it is necessary to perform cancer screening and imply a possible treatment.
- At cardiomyopathy coronary angiography is performed. This study allows to select patients in whom coronary artery bypass grafting (with correction of the valve disease), angioplasty with stenting may be performed.
- Echo cardiography is performed: ejection fraction is determined, the monitoring of a cardiac function in patients on the waiting list for a heart transplant is initiated. Ejection fraction of less than 25% indicates a poor prognosis for long-term survival.
- In order to exclude other pathology of the chest X-ray is performed, perhaps in two projections.
- In order to evaluate pulmonary function the examination of respiratory function is conducted. Severe non-corrective chronic lung disease is a contraindication to heart transplantation.
- With a view to assess the global heart function, the maximum oxygen consumption (MVO2) is determined. This indicator is a good predictor of the severity of heart failure, and correlates with survival. MVO2 below 15 indicates a poor prognosis of one-year survival.
Diagnostic invasive procedures
Endomyocardial biopsy of the myocardium in candidates for heart transplantation is not performed routinely. It is possible to carry out this procedure when there is a suspicion that the cardiomyopathy is a consequence of the system process (eg, collagenoses).
A system process is a contraindication to heart transplantation.
The evaluation of the heart and lungs also includesthe catheterization of the right compartments of the heart. This allows to determine the reversibility of the pulmonary vascular changes and the possibility of other treatments. An important indicator is the pulmonary vascular resistance. Patients with stable pulmonary vascular resistance of more than 4 units do not require heart transplantation, due to irreversible changes in pulmonary circuit. When pulmonary vascular resistance by 2 to 4 Wood units takes place,a test with vasodilators (and/or cardiotonic) is conducted with a view to check the reversibility of these pathological changes. If the changes are possible to reverse,the heart transplantationmay be performed, but the risk of complications in this case increases.
Drug therapy for the recipient before the heart transplantation
During the waiting period of the donor organ a constant monitoring and a regular inspection of the candidate is conducted; This draws attention to the signs of further deterioration in the heart function. Patients receive standard therapy for a heart failure. The treatment and monitoring is carried out in close contact with the transplantolgy center.
In the case of a clinical deterioration the hospitalization into the center of transplantation and cardiac surgery is required for the implantation of aventricular assist device - ventricular bypass - or for the moving the patient up the waiting list. It is important tokeep in mind that the patient's condition may deteriorate to the extent that the transplant will not be efficient due to the irreversible changes in end organs (lungs, liver). The questions regarding the preoperative management of candidates for a heart transplantation are complex and require the participation of qualified professionals, the patient, his/her relatives, and a direct contact with the transplantology center.