HEART TRANSPLANT: FINDING DONORS IS DAUNTING!
A heart transplant is unquestionably the most serious operation a human can have. Removing a person’s heart is a terminal event. Unless the patient’s circulation is maintained by a mechanical device called a cardiopulmonary bypass, or a mechanical heart, he or she will die. Even though the operation, itself, is complex technically, the most difficult aspect of a heart transplant is finding a donor. Yes, potential donors die every day, but they may not be suitable candidates for a recipient. Their tissue factors may not match those of the person in need, or their survivors may refuse organ harvesting (removing their organs for transplantation). In the U.S., 106,000 people are on the waiting list to have a heart transplant. If there are between 2000-3000 heart transplants done in the U.S. annually; clearly, a lot of people don’t survive long enough until a donor is identified.
Additionally, the donor must not only be brain dead, but he/she must also be on life support to keep the heart beating. Extensive laboratory evaluation is also needed to determine if the blood and tissue factors specific to the donor and the recipient are a match. If they don’t match, rejection of the transplanted organ is a certainty.
Heart transplantation was first performed in 1967. In the 1980’s, with the introduction of anti-rejection drugs, and the use of techniques to detect early rejection, survival statistics for heart transplant improved well enough for it to become a viable option for end-stage heart failure. In the last ten years, 31,328 heart transplants have been done, worldwide. A Canadian man is the longest surviving heart transplant recipient. As of May, 2021, his record was 34 years, 359 days. Another 14 months later, I was unable to find if he is still living. The median survival after heart transplant is 12.5 years. Survival rates obviously decline as the heart ages. The one year survival rate is 85-87%, five year rate is 69%, and after 10 years, 57%. The donor heart must be under 55 years of age. The oldest recipient was 67 years old, and the longest surviving American is a Green Bay, WI man who as of June, 2021 was approaching 35 years.
The only heart transplant patient I knew was Wiley Embry, a south side Indianapolis man, who at age 38 underwent “five unsuccessful bypass surgeries.” His heart function deteriorated so severely, afterward, he had to retire. After waiting 26 months, he had a heart transplant. His operation gave him a second chance at life. For the next 24 years, he lived as normally as anyone and even competed in the transplant patient Olympics. But after surviving for 24 years, he suddenly died in his sleep at the age of 72. Embry was well-known by the south side medical community. He was a patient of the Indiana Heart Physician’s group and became a friend of many physicians. We all marveled at his longevity as well as his optimism and enthusiasm in spite of his serious situation.
There are many heart diseases that damage or weaken the heart so severely that the only alternative to death is a heart transplant. Hypertrophic cardiomyopathy (HCM) is such a condition. In HCM, the heart muscle (myocardium), for unknown reasons, thickens excessively and is unable to effectively pump the blood to maintain adequate circulation. Shortness of breath and extreme weakness are the major symptoms. Over time the patient’s health worsens, and he/she become bedfast. Patients with HCM often require a cardiac defibrillator because the weakened myocardium is very susceptible to serious arrhythmias.
Heart failure eventually develops, the patient reaches a terminal state, and heart transplant becomes the only procedure left. It is lifesaving if complications or rejection are prevented. But as I stated before, finding donors is a problem. Unlike our kidneys, we only have one heart. Kidney transplants are done more often because a lot of people are willing to donate one of their kidneys to a matched recipient. One can live normally with only one kidney. The heart is different. Voluntary donation is existent only posthumously.
However, “the need for lifesaving organ transplants exceeds the availability of transplantable organs….in 2021, approximately 12,000 patients died or developed complications that precluded them from receiving a transplanted organ…..the first step…..is to be placed on a national waiting list, ranked according to objective clinical criteria intended to reflect medical necessity.” The sickest patients are prioritized. Financial resources are also factored, and that can influence the order in which some patients are chosen with well-insured individuals transplanted first. The issue of organ compatibility is a selection criterion as well.
Rejection is the biggest problem after heart transplantation and occurs when the recipients immune system detects a foreign object has entered the patient’s body. Rejection occurs for a number of reasons, all of which are related to reactions by the immune system, and based on when they occur, are classed as:
Hyper-acute—occurring a few minutes after transplantation
Acute—occurring any time from one week to 3 months after transplant
Chronic—occurring over many years; constant attacks by the immune system damage
the transplanted organ
The risk of rejection is highest in the first six months after transplantation. Women, young adults, and African Americans have a greater risk. Numerous anti-rejection drugs are currently available for use. The list includes prednisone (a corticosteroid), tacrolimus (Prograf), cyclosporine (Neoral), mycophenolate mofetil (CellCept), azathioprine (Imuran), rapamycin (Rapamune, Sirolimus).
Anti-rejection drugs are used, first as Induction agents given at the time of the transplant, or as Maintenance agents to protect the transplanted organ long term. According to the National Kidney Foundation, the most commonly used combination is the following:
Tacrolimus (Prograf)
Mycophenolate Mofetil (CellCept)
Prednisone
Cyclosporine and Sirolimus are prescribed often, as well, but this is beyond the scope of this blog.
Rejection causes symptoms, but by the time symptoms occur, it’s often too late to save the heart. To address that problem, scientists have developed biopsy techniques to detect signs of rejection early. Called endomyocardial biopsy, at pre-determined intervals, samples of the inner lining of the heart are taken for analysis. If signs of rejection are found, adjustments to the dose and combination of anti-rejection drugs is made. A biopsy of this type is no small thing since it is invasive and similar to a heart catheterization.
Other complications such as infection, bleeding, and an unusual form of coronary artery disease occur as well. Cardiac allograft vasculopathy (CAV) is a progressive thickening of the walls of the coronary arteries that is often responsible for the death of transplant patients after five years. It appears to be caused by severing of nerves to the heart occurring during organ harvesting and transplantation. Our old friends, statin drugs, are helpful post-transplant for preventing CAV.
“Solid organ transplantation is one of the greatest medical achievements of the 20th century.” Heart transplantation is an example of a complex, highly risky, and expensive procedure, but according to an editorial in JAMA it “remains out of reach for too many.” Inequities in selection and preference for the well-insured over welfare patients portends bias. That is for another discussion, however.
Heart transplantation improves survival and the quality of life for patients with advanced heart failure. Since the potential for severe complications is quite high, cardiac transplantation is “not a definitive cure” for heart failure. It does give thousands of patients a new life, but a life that is not guaranteed. Multiple problems can occur. Although those extra years are physically rewarding, they are emotionally very difficult knowing you carry a higher than normal risk of death. Any day could be your last. Living with this knowledge is a psychological burden, but every day of improved quality of life is a bonus!
References: Alba AC, et al. Complications after Heart Transplantation: Hope for the Best, but Prepare for the Worst. Int J Transpl Res & Med. 2:022.
“Wiley Embry was a man with a tremendous heart.” Indianapolis Star 2015 Oct 13.
Frigerio M, Oliva F, et al. Changes in patient survival and quality of life after heart transplantation. G Ital Cardiol 2008 Jul;9(7):461-471.
Zhuo DX, Ginder K, Hardin EA. Markers of Immune Function in Heart Transplantation: Implications for Immunosuppression and Screening for Rejection. Current Heart Fail Rep 2021 Apr;18(2):33-40.
Kilic A, et al. Donor Selection in heart transplantation. J Thoracic Dis 2014;6(8):1097-1104.
Wadhwani SI, Lal, JC, Gottlieb LM. Medical Need, Financial Resources, and Transplant Accessibility. JAMA 2022 April 19;327(15):1445-1446.
