Flashcards in Chapter 281 - Cardiac Transplantation and Prolonged Assisted Circulation Deck (35):
Name the current therapeutic options for extraordinary life-extending measures due to advanced heart-failure.
"Current therapeutic options are limited to cardiac transplantation (with the option of mechanical cardiac assistance as a "bridge" transplatation) or permanent mechanical assitance of the circulation."
Are there any experimental therapies for advanced heart failure?
"In the future, it is possible that genetic modulation of ventricular function or cell-based cardiac repair will be option for such patients. Currently, both of the latter approaches are considered to be experimental."
Briefly explain the history behind cardiac transplantation. How many heart transplants are performed globaly and in the United States?
"Surgical techniques for orthotopic transplantation of the heart were devised in the 1960s and taken into the clinical arena in 1967. The procedures did not gain widespread clinical acceptance until the introduction of "modern" and more effective immunossupression in the early 1980s. By the 1990s, the demand for transplantable hearts met, and then exceeded, the available donor worldwide, acoording to data from the Registry of the International Society for Heart and Lung Transplantation (ISHLT). Subsequently, heart transplantation activity in the United States has remained stable at ~2200 per year, but worldwide activty reported to this registry has decreased somewhat. This apparent decline in numbers may be a result of the fact that reporting is legally mandated in the United States but not elsewhere, and several countries have started their own databases."
When was the first heart transplant performed?
Describe the surgical technique for heart transplant as well as the latter technique modifications.
"Donor and recipient hearts are excised in virtually identical operations with incisions made across the atria and atrial septum at mid-atrial level (with posterior walls of the atria left in place) and across the great vessels just above the semilunar valves. The donor heart is generally "harvested" by a separate surgical team, transported from the donor hospital in a bag of iced saline solution, and reanastomosed into the waiting recipient in the orthotopic or normal anatomic position. The only change in surgical technique since this methoed was first described has been a movemenet in recent years to move the right atrial anastomosis back to the level of the superior and inferior venae cavae to better preserve right atrial geometry and prevent atrial arrhythmias."
Is the transplated heart enervated and, if not, does it respond to physical activity as the normal heart would?
"Both methods of implantation leave the recipient with a surgically denervated heart that does not respond to any direct sympathetic or parasympathetic stimuli but does respond to circulating catecholamines. The physiologic responses of the denervated heart to the demands of exercise are atypical but quite adequate for continuation of normal physical activity."
Explain the priority system for heart transplant decision in the United States.
In the United States, the allocation of donor organs is accomplished under the supervision of the United Network for Organ Sharing, a private organization under contract to the federal government. The United States is divided geographically into eleven regions for donor heart allocation. Allocation of donor hearts wihin a region is decided according to a system of priority that takes into account (1) the severity of illness, (2) the geographic distance from the donor, and (3) the patient's time on the waiting list. A physiologic limit of ~3h of "ischemic" (out-of-body) time for hearts precludes a national sharing responsive to input from a variety of constituencies, including both donor families and transplantation professionals."
Matching is generally based on HLA system.
True or False?
"matching generally is based only on compatibility in terms of AB0 blood group and gross body size."
"While HLA matching of donor and recipient would be ideal, the relatively small numbers of patients as well as the time contraints involved make such matching impractical."
What are the patients considered of highest priority?
"At the current time, the highest priority according to severity of illness is assigned to patients requiring hospitalization at the transplantation center for IV inotropic support, with a pulmonary artery catheter in place for hemodynamic monitoring, or to patients requiring mechanical circulatory support - i.e., use of an intra-aortic balloon pump or a right or left ventricular assist device (RVAD, LVAD), extracorporeal membrane oxygenation, or mechanical ventilation."
"The second highest priority is given to patients requiring ongoing inotropic support, but wihout a pulmonary artery catheter in place. All other patients are assigned a priority accorind to time accrued on the waiting list"
Regarding HLA-matching, one should one use prospective cross-matching before heart transplantation?
"some patients who are "presensitized" and have preexisting antibodies to human leukocyte antigens (HLAs) undergo prospective cross-matching with the donor; these patients are commonly multiparous women or patients who have received multiple transfusions."
What are the indications and contraindications for heart transplantation?
"Heart failure is an increasingly common cause of death, particularly in the elderly. Most patients who reach what has recently been categorized as stage D, or refractory end-stage heart failure, are appropriately treated with compassionate end-of-life care. A subset of such patients who are younger and without significant comorbidities can be considered as candidates for heart transplantation. Exact criteria vary in different centers but generally take into consideration the patients physiologic age and the existence of comorbidities such as peripheral or cerebrovascular disease, obesity, diabetes, cancer or chronic infection."
What is the survival rate after heart transplantation?
"A registry organized by the ISHLT has tracked worldwide and U.S survival rates after heart transplantation since 1982. The most recent update reveals survival rates of 83% and 76% 1 year and 3 years after transplantation, respectively, or a posttransplatation "half-life" of 10.00 years. The quality of life of survivors is generally excellent, with well over 90% of patients in the registry returning to normal and unrestricted function after transplantation."
Which drugs are usually used for imunossupression induction regarding heart transplant?
"Most cardiac transplantation programs currently use a three-drug regimen that includes a calcineurin inhibitor (cyclosporine or tacrolimus), an inhibitor of T cell proliferation or differentiation (azathioprine, mycophenolate mofetil, or sirolimus), and at least a short initial course of glucocorticoids. Many programs also include an initial "induction" course of polyclonal or monoclonal antibodies to T cells in the perioperative period to decrease the frequency or severity of early posttransplantation rejection. Most recently introduced have been monoclonal antibodes (daclizumab and basiliximab) that block the interleukin 2 receptor and may prevent allograft rejection without additional global immunosuppresion."
How does one detect rejection of the heart allograft?
"Cardiac allograft rejection is usually diagnosed by endomyocardial biopsy conducted either on a surveillance basis or in response to clinical deterioration. Biopsy surveillance is performed on a regular basis in most programs for the first year postoperatively (or the first 5 years in many programs). Therapy consists of augmentation of immunosupression, the intensity and duration of which are dictated by the severity of rejection."
Survivours of heart transplant might be susceptible to coronary artery disease (CAD). Compare this phenomenon with the "ordinary" atherosclerosis for non-transplanted population.
"Despite usually having young donor hearts, cardiac allograft recipients are prone to develop coronary artery disease (CAD). This CAD is generally a diffuse concentric, and longitudinal process that is quite different from "ordinary" atherosclerosis CAD, which is more focal and often eccentric."
How does one explain the susceptibility of heart allograft recipients to coronary artery disease (CAD)?
"The underlying etiology most likely is primarily immunologic injury of the vascular endothelium, but a variety of risk factors influence the existence and progression of CAD, including nonimmunologic factors such as dyslipidemia, diabetes mellitus, and cytomegalovirus (CMV) infection."
The newer immunosupressive agents might be associated with less risk of heart transplant recipients to develop coronary artery disease (CAD).
True or False?
"Thus far, the immunosupressive agents mycophenolate mofetil and the mammalian target of the rapamycin (mTOR) inhibitors sirolimus and everolimus have been shown to be assocaited with short-term lower incidence and extent of coronary intimal thickening; in anecdotal reports, institution of sirolimus was associated with some reversal of CAD."
Since heart transplant recipients are susceptible to early coronary artery disease, should one administer statins to this population?
"The use of statins also is associated with a reduced incidence of this vasculopathy, and these drugs are now used almost universally in transplant recipients unless contraindicated."
Heart transplant recipients develop early coronary artery disease and thus, angina pectoris is a common complaint in these patients.
True or False?
"Because of the denervated status of the organ, patients rarely experience angina pectoris, even in advanced stages of disease."
Since heart transplant recipients are exposed to chronic immunosupressive therapy, there is an increased risk for malignancy. Which malignancies are those and how can one manage them?
"Lymphoprolifrative disorders are among the most frequent posttransplantation complications and, in most cases, seem to be driven by Epstein-Barr virus. Effective therapy includes reduction of immunosupression (a clear "double-edged sword" in the setting of a life-sustaining organ), administration of antiviral agents, and traditional chemo- and radiotherapy. Most recently, specific antilymphocyte (CD20) therapy has shown great promise. Cutaneous malignancies (both basal cell and squamous cell carcinomas) also occur with increased frequency among transplant recipients and can follow aggressive courses. The role of decreasing immunosupression in the treatment of these cancers is far less clear."
The incidence of infectious complications has reduced since the introduction of cyclosporine.
True or False?
Infections with unusual and opportunistic organisms are still the major cause of death during the first postoperative year and remain a threat to the chronically immunosupressed patient throughout life.
True or False?
Name two common opportunistic agents that one should easily recognize in heart transplant recipients.
CMV and Aspergillus infection.
Briefly explain the history behind prolonged assisted circulation and total artiicial hearts.
"The modern era of mechanical circulatory support can be traced back to 1953, when cardiopulmonary bypass was first used in a clinical setting and ushered in the possibility of brif periods of circulatory support to permit open-heart sugery. Subsequently, a variety of extracorporeal pumps to provide circulatory support for brief periods have been developed. The use of a mechanical device to support the circulation for more than a few hours initially progressed slowly, with the implantation of a total artificial heart in 1969 in Texas by Cooley. The patient survived for 60 h until a donor organ becamse available, at which point he underwent transplantation. Unfortunately, the patient died of pulmonary complications after transplantation. The entire fireld of mechanical replacement of the hrat then took a decade-long hiatus until the 1980s, when total artificial hearts were reintrotuced with much publicity; however, they failed to produce the hoped-for-treatment of end-stage heart disease. Starting in the 1970s, in parallel with the development of the total artificual heart, intense reaserach had addressed the development of ventricular assist devices, which provide mechanical assistance for (rather than replacing) the failing ventricle."
LVADs (Left-Ventricle Assistance Devices) are an alternative to heart transplant.
True or False?
"Although conveived of initiatlly as alternatives to biologic replacement of the heart, LVADs were introduced - and are still employed primarily - as temporary "bridges" to heart transplantation in candidates in whom medical therapy begins to fail befdore a donor heart comes available."
What are the current indications for ventricular assist devices?
"Currently, there are two major indications for ventricular assitance. First, patients at risk of imminent death from cardiogenic shock are eligible for mechanical support. These patients are generally managed with temporary cardiac assist devices. Second, if patients have a left ventricular ejection fraction less than 25% or a peak VO less than 14 mL/kg per min or are dependent on inotropic therapy or support with intraaortic balloon counterpulsation, they may be eligible for mechanical support."
Which two major types of ventricular assist devices are there available? How should one describe its mechanisms of action?
"Pulsatile devices are ventricular assist devices whose mechanism of action mandates the alternating filling and emptying of a volume chamber within the device that mimics the mechasnism of action of the natural heart. Nonpulsatile devices have a mechanism of action that results in continuous blood flow through the device, eliminating the need for pulsatility."
What are the main advantages and disadvantages of pulsatile devices in comparison to nonpulsatile ones?
"The pulsatile devices are larger, bulkier, and associated with greater energy requirements and higher rates of complications than the nonpulsatile devices. However, pulsatile devices provide greater degrees os support and may even be capable of replacing the function of the heart entirely in the form of a total artificial heart. Bcause of the bulkiness of these devices, many patients are too small to be supported with intracorporeal pulsatile pumps. However, paracorporeal versions are available. These devices are versatile and can be used for right, left, or biventricular assistance/replacement."
Which types of nonpulsatile devices are there? What are the different features of each one?
Continuous-flow (nonpulsatile) devices are further categorized on the basis of impeller design and mechanism. The older designs have tended to be axial-flow pumps, which operate on the Archimedes scre principle. These devices have an impeller that is in line with the direction of blood flow, and the inlet direction of blood is the same as the outlet direction."
"The newer devices are centrifugal in design; the blood flow takes a 90º turn between the inlet section of the pump and the outlet section. Another major difference in the newer devices is the absence of blood-washed bearing (with most devices having magnetically leviated impellers). This design allows the construction of smaller pumps with less blood-element activation than the axial-flow designs."
Name the major indications for short-term support with ventricular assistance devices.
"A number of other devices are approved only for short-term support in post-cardiac surgery shock or in cardiogenic shock secondary to acute myocardial infarction or fulminant myocarditis"
Name the only FDA-approved device for severe biventricular failure.
Syncardia, Tucson, AZ - pneumatic, biventricular, orthotopically implanted ventricular assist device with an externalized driveline connecting it to its console.
Name the only FDA-approved device that can be used as destination therapy.
HeartMate II LVAD (Thoratec) - it uses a drainage canula in the left ventricular apex to drain blood into a small chamber, where the blood is driven by an electrically powered motor that spins a rotor, accelerating blood outflow into the asceindg aorta.
What is the only FDA-approved third generation heart pump?
HeartWare Ventricular Assit System with the HVAD pump (HeartWare Inc., Framingham, MA) - centrifugal pump that is housed completely within the patient's pericardial cavity.
Regarding young patients with a ventricular assistance device as "bridging" to heart transplantation, how many are transplated in the first year?