Building a Bridge to Heart Transplantation
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《新英格兰医药杂志》
He who saves one life, saves the world entire.
— Hebrew proverb, quoted in
Thomas Keneally, Schindler's List
End-stage heart failure, characterized by marked symptoms at rest or with minimal activity despite optimal therapy, is designated as stage D heart failure. Frequent, recurring exacerbations may often be treated successfully, but decline is inevitable and life expectancy with medical therapy alone is short (survival rates are below 50 percent at one to two years) (see Figure). The addition of palliative measures, such as continuous infusions of inotropic drugs and hospice-like care, may be considered. Cardiac transplantation or permanent mechanical circulatory support is possible only in a select few patients.
Figure. The Course of Stage D Heart Failure.
As hemodynamic status deteriorates in a patient with stage D heart failure, metabolic, cellular, and nutritional health is compromised. The deterioration is marked by frequent exacerbations that may often be treated successfully. Although signs and symptoms of progressive heart failure predominate, the risk of sudden death is also present (dotted lines). Heart transplantation early in the course is associated with excellent results, whereas later transplantation is less successful. Mechanical circulatory support decreases the likelihood of death before transplantation can be performed; restores metabolic, cellular, and nutritional health; and improves the likelihood of successful transplantation in most candidates for heart transplantation. The optimal use of donor hearts is enhanced. Such support appears to be warranted when the patient's health has deteriorated into the red zone, whereas patients with health in the green zone can safely undergo transplantation without prior mechanical circulatory support. NYHA denotes New York Heart Association.
When candidates for heart transplantation have hemodynamic deterioration, metabolic, cellular, and nutritional compromise follow, and the likelihood of survival after transplantation diminishes. Even among patients with moderately compromised function, the likelihood of post-transplantation survival exceeds 80 percent at one year. However, as hemodynamic compromise progresses from moderate to severe, not only is there an increase in the risk of dying before transplantation can be performed, but the results after transplantation also worsen. The timely use of mechanical circulatory support halts further deterioration; decreases the likelihood of death before transplantation can occur; and reverses metabolic, cellular, and nutritional compromise. The temporary use of such support thus permits heart transplantation with a greater expectation of long-term survival and a better quality of life.
The temporary use of mechanical circulatory support before transplantation, known as "bridging," is not to be confused with mechanical circulatory support intended from the outset to be permanent treatment, known as "destination therapy." Bridging is reserved for candidates for transplantation, and success is measured in terms of the proportion of patients surviving to successful heart transplantation.
Since a variety of bridging devices are commercially available, the selection of a device depends on the type of heart failure, the size of the patient, the surgeon's experience, and the institutional preference. Implantable left ventricular assist devices channel blood from the left ventricle to the pump, which then circulates blood to the aorta. The currently available implantable devices are too large for patients with a body-surface area of less than 1.5 m2, but investigations with smaller devices are ongoing. Meanwhile, paracorporeal devices, with the pump placed outside of the body, provide an alternative for the support of one or both ventricles. Left ventricular assist devices are generally inadequate for bridging to transplantation in patients with severe biventricular heart failure, which requires the use of two paracorporeal devices.
When left ventricular assist devices or paracorporeal devices are either difficult to use or contraindicated, the replacement of both ventricles with an implantable device such as a total artificial heart may be warranted. Such circumstances frequently arise in patients with severe aortic insufficiency, intractable ventricular arrhythmias, an aortic prosthesis, an acquired ventricular septal defect, or irreversible biventricular failure requiring a high pump output. In this issue of the Journal, Copeland and colleagues (pages 859–867) show that the CardioWest artificial heart (SynCardia Systems) provides a successful bridge to transplantation in most severely compromised patients and that those whose cardiac function is so bridged do better than similarly compromised patients who instead undergo emergency transplantation. The use of the artificial heart studied by these investigators is generally restricted to patients with a body-surface area of at least 1.7 m2.
Given the overwhelming and growing prevalence of heart failure, why does a report of a nonrandomized study demonstrating successful bridging to transplantation in relatively few patients warrant attention? Since the 1980s, more than 6 million people have died of heart failure in the United States alone. A mere fraction of that group — fewer than 50,000 patients — received transplants. An even smaller number have required mechanical circulatory support before transplantation — a total artificial heart was used in fewer than 500 patients, and left ventricular assist devices in approximately 5000 patients. Some public health officials have derided heart transplantation as obscenely irrelevant; then how relevant is the use of an artificial heart as a bridge to transplantation? Others have argued that bridging to transplantation is much ado about very little, since suitable candidates are always available for transplantation. In short, why bother?
Here's why. A 52-year-old entrepreneur, father of four, grandfather of one, lay dying in an intensive care unit with severe, end-stage, biventricular heart failure. He had been on the waiting list for transplantation for more than a year. Hemodynamic compromise led to incipient renal and hepatic failure. Just 12 hours previously, he had had a cardiac arrest and became obtunded. Cardiogenic shock persisted despite the use of an intraaortic balloon pump and high intravenous doses of inotropic drugs. This doomed man, typical of those whom Copeland and colleagues studied, then received an artificial heart. Had emergency transplantation been performed instead, the likelihood of post-transplantation survival would have been dismal (see Figure), and the donor heart, a very precious commodity, would most likely have been squandered. After the implantation, however, the patient's metabolic, cellular, and nutritional abnormalities resolved. Four months later, he received a transplant. During the subsequent 10 years, he has been able to do all he chooses, living a vigorous and rewarding life. As is typical of heart-transplant recipients, the patient has medical follow-up visits two to four times each year.
Joseph Lister did not need a randomized, controlled trial to prove that an antiseptic approach benefited patients with compound fractures. No more than one administration of ether inhalation by William Morton at an operation at the Massachusetts General Hospital in 1846 was necessary to convince skeptical surgeons about the potential of general anesthesia. Nor should it take more than this report regarding the use of the artificial heart as a bridge to transplantation in certain patients to convince us of the triumph of medical technology in helping patients in dire circumstances.
Although not all patients with heart failure can currently be saved, the Hippocratic ideal holds: we are honor-bound to serve as advocates for individual patients. Therefore, we should not condemn the artificial heart for failing to save all patients with heart failure. Rather, we should embrace this technology because it increases our ability to help some patients, like the man described above. The artificial heart is not "a bridge too far," but a triumph for the afflicted patient. Like Oskar Schindler, we may not be able to save all people in need, but one life is worth the effort.
Source Information
From the Division of Cardiology, University of Utah School of Medicine, and LDS Hospital — both in Salt Lake City.
Related Letters:
A Bridge to Heart Transplantation
Boltwood C. M. Jr., O'Leary M. J., Copeland J. G., Renlund D. G., Kfoury A. G., Renlund A. R.(Dale G. Renlund, M.D.)
— Hebrew proverb, quoted in
Thomas Keneally, Schindler's List
End-stage heart failure, characterized by marked symptoms at rest or with minimal activity despite optimal therapy, is designated as stage D heart failure. Frequent, recurring exacerbations may often be treated successfully, but decline is inevitable and life expectancy with medical therapy alone is short (survival rates are below 50 percent at one to two years) (see Figure). The addition of palliative measures, such as continuous infusions of inotropic drugs and hospice-like care, may be considered. Cardiac transplantation or permanent mechanical circulatory support is possible only in a select few patients.
Figure. The Course of Stage D Heart Failure.
As hemodynamic status deteriorates in a patient with stage D heart failure, metabolic, cellular, and nutritional health is compromised. The deterioration is marked by frequent exacerbations that may often be treated successfully. Although signs and symptoms of progressive heart failure predominate, the risk of sudden death is also present (dotted lines). Heart transplantation early in the course is associated with excellent results, whereas later transplantation is less successful. Mechanical circulatory support decreases the likelihood of death before transplantation can be performed; restores metabolic, cellular, and nutritional health; and improves the likelihood of successful transplantation in most candidates for heart transplantation. The optimal use of donor hearts is enhanced. Such support appears to be warranted when the patient's health has deteriorated into the red zone, whereas patients with health in the green zone can safely undergo transplantation without prior mechanical circulatory support. NYHA denotes New York Heart Association.
When candidates for heart transplantation have hemodynamic deterioration, metabolic, cellular, and nutritional compromise follow, and the likelihood of survival after transplantation diminishes. Even among patients with moderately compromised function, the likelihood of post-transplantation survival exceeds 80 percent at one year. However, as hemodynamic compromise progresses from moderate to severe, not only is there an increase in the risk of dying before transplantation can be performed, but the results after transplantation also worsen. The timely use of mechanical circulatory support halts further deterioration; decreases the likelihood of death before transplantation can occur; and reverses metabolic, cellular, and nutritional compromise. The temporary use of such support thus permits heart transplantation with a greater expectation of long-term survival and a better quality of life.
The temporary use of mechanical circulatory support before transplantation, known as "bridging," is not to be confused with mechanical circulatory support intended from the outset to be permanent treatment, known as "destination therapy." Bridging is reserved for candidates for transplantation, and success is measured in terms of the proportion of patients surviving to successful heart transplantation.
Since a variety of bridging devices are commercially available, the selection of a device depends on the type of heart failure, the size of the patient, the surgeon's experience, and the institutional preference. Implantable left ventricular assist devices channel blood from the left ventricle to the pump, which then circulates blood to the aorta. The currently available implantable devices are too large for patients with a body-surface area of less than 1.5 m2, but investigations with smaller devices are ongoing. Meanwhile, paracorporeal devices, with the pump placed outside of the body, provide an alternative for the support of one or both ventricles. Left ventricular assist devices are generally inadequate for bridging to transplantation in patients with severe biventricular heart failure, which requires the use of two paracorporeal devices.
When left ventricular assist devices or paracorporeal devices are either difficult to use or contraindicated, the replacement of both ventricles with an implantable device such as a total artificial heart may be warranted. Such circumstances frequently arise in patients with severe aortic insufficiency, intractable ventricular arrhythmias, an aortic prosthesis, an acquired ventricular septal defect, or irreversible biventricular failure requiring a high pump output. In this issue of the Journal, Copeland and colleagues (pages 859–867) show that the CardioWest artificial heart (SynCardia Systems) provides a successful bridge to transplantation in most severely compromised patients and that those whose cardiac function is so bridged do better than similarly compromised patients who instead undergo emergency transplantation. The use of the artificial heart studied by these investigators is generally restricted to patients with a body-surface area of at least 1.7 m2.
Given the overwhelming and growing prevalence of heart failure, why does a report of a nonrandomized study demonstrating successful bridging to transplantation in relatively few patients warrant attention? Since the 1980s, more than 6 million people have died of heart failure in the United States alone. A mere fraction of that group — fewer than 50,000 patients — received transplants. An even smaller number have required mechanical circulatory support before transplantation — a total artificial heart was used in fewer than 500 patients, and left ventricular assist devices in approximately 5000 patients. Some public health officials have derided heart transplantation as obscenely irrelevant; then how relevant is the use of an artificial heart as a bridge to transplantation? Others have argued that bridging to transplantation is much ado about very little, since suitable candidates are always available for transplantation. In short, why bother?
Here's why. A 52-year-old entrepreneur, father of four, grandfather of one, lay dying in an intensive care unit with severe, end-stage, biventricular heart failure. He had been on the waiting list for transplantation for more than a year. Hemodynamic compromise led to incipient renal and hepatic failure. Just 12 hours previously, he had had a cardiac arrest and became obtunded. Cardiogenic shock persisted despite the use of an intraaortic balloon pump and high intravenous doses of inotropic drugs. This doomed man, typical of those whom Copeland and colleagues studied, then received an artificial heart. Had emergency transplantation been performed instead, the likelihood of post-transplantation survival would have been dismal (see Figure), and the donor heart, a very precious commodity, would most likely have been squandered. After the implantation, however, the patient's metabolic, cellular, and nutritional abnormalities resolved. Four months later, he received a transplant. During the subsequent 10 years, he has been able to do all he chooses, living a vigorous and rewarding life. As is typical of heart-transplant recipients, the patient has medical follow-up visits two to four times each year.
Joseph Lister did not need a randomized, controlled trial to prove that an antiseptic approach benefited patients with compound fractures. No more than one administration of ether inhalation by William Morton at an operation at the Massachusetts General Hospital in 1846 was necessary to convince skeptical surgeons about the potential of general anesthesia. Nor should it take more than this report regarding the use of the artificial heart as a bridge to transplantation in certain patients to convince us of the triumph of medical technology in helping patients in dire circumstances.
Although not all patients with heart failure can currently be saved, the Hippocratic ideal holds: we are honor-bound to serve as advocates for individual patients. Therefore, we should not condemn the artificial heart for failing to save all patients with heart failure. Rather, we should embrace this technology because it increases our ability to help some patients, like the man described above. The artificial heart is not "a bridge too far," but a triumph for the afflicted patient. Like Oskar Schindler, we may not be able to save all people in need, but one life is worth the effort.
Source Information
From the Division of Cardiology, University of Utah School of Medicine, and LDS Hospital — both in Salt Lake City.
Related Letters:
A Bridge to Heart Transplantation
Boltwood C. M. Jr., O'Leary M. J., Copeland J. G., Renlund D. G., Kfoury A. G., Renlund A. R.(Dale G. Renlund, M.D.)