Heart transplantation vs long-term mechanical assist devices: clinical equipoise?

Abstract

Heart transplantation became a clinical entity in 1967, but reached clinical viability in the early 1980s. Since the first heart transplant the donor’s age has increased, as has the recipient’s. The length of stay for the initial hospitalization has decreased. The time to the first rejection episode has increased. Long-term survival has also improved [1]. The current generation of mechanical assist devices was born in the early 1990s, if we exclude the experience with an artificial heart in 1982. Their clinical usage has steadily increased since the REMATCH trial was published in 2001 [2]. The criteria for destination therapy continue to evolve as we learn more about patient selection and management. For this editorial, let us exclude total artificial hearts, as the experience is limited. There are certain patients who cannot benefit from placement of a left ventricular assist device (LVAD) alone. These are patients with pronounced right ventricular failure, as well as patients with protracted arrhythmias. Those with a restrictive cardiomyopathy do not have a large enough left ventricular chamber to receive an LVAD. Hypertrophic cardiomyopathy patients have too-thick a left ventricle to receive a functioning LVAD. Finally, what about patients who have received various palliative procedures for a single ventricle? Heart transplantation is the appropriate procedure for them [3]. At the University of Minnesota, there have been patients who required temporary biventricular support as a bridge to an implantable LVAD. They underwent eventual LVAD explant and heart transplantation, but then required temporary right ventricular assist support. How long will insurance companies pay for this much surgery? How many patients will recover from this much time in the hospital? All of these operations increase the patient’s exposure to blood products. This increases the number of patients who are sensitized. Sensitized patients increase the challenges of suppressing rejection and infection after heart transplantation. The patient with multiple cardiac operations as well as multiple cardiac catheterizations may develop complications from these treatments such as heparin-induced thrombocytopenia. All programmes are becoming more experienced in dealing with this problem. Plasmapheresis or bivalirudin offer solutions, but it is better to avoid the condition entirely. With obese patients, there is a patient-heart mismatch that contributes to the development of heart failure. Dealing with the obesity epidemic in terms of prevention would cut down on the number of patients requiring a heart transplant or LVAD. There are patients with significant fixed pulmonary hypertension or recent malignancy who are not candidates for heart transplantation. A transpulmonary gradient of ≥15 would mean that the patient should be considered for LVAD over heart transplantation. A patient with a malignancy within the past 5 years should also be considered a candidate for LVAD over heart transplantation. Any evidence of ongoing infection makes the patient a poor candidate for either procedure. The very-sensitized patient is also one who should be considered for a destination LVAD. According to the most recent report of the Registry of the International Society for Heart and Lung Transplantation, the median survival of 96 273 adult and paediatric heart recipients is 10 years [4]. Those who survive 1 year have a 63% chance of living 10 years and a 27% chance of living 20 years. Recipients of ventricular assist devices are significantly fewer in number and post-procedure years. Dr Kirklin presented the Interagency Registry of Mechanically Assisted Circulatory Support (INTERMACS) data on patients who received a continuous-flow LVAD as destination therapy [5]. The patients who were not in cardiogenic shock at the time of implantation were the most favourable group for good outcomes. These patients had survival of 88 and 80% at 1 and 2 years, respectively. The mortality rate for these patients was 10% per year. After heart transplantation, it is 6% per year. Moreno et al. [6] used a probabilistic Markov model to estimate the cost-effectiveness of the HeartMate II LVAD (Thoratec, Pleasanton, CA, USA). They found that the HeartMate II had a mean cost per quality-adjusted life-year of $414 275. The cost of the device alone was $150 720. Medical management of patients awaiting transplant has improved since the REMATCH trial. At least in the UK, the HeartMate II LVAD is not judged to be costeffective as a bridge to transplantation. According to OPTUM health, in the USA a heart transplant hospitalization costs $550 000. The hospitalization for a patient receiving an LVAD is $400 000, beginning on the day that the LVAD is implanted. Length of stay depends on how sick the patient is at the time of transplant or implant. Clinical equipoise suggests that there is true uncertainty about which of two potential clinical treatments is appropriate for a