Acute pump failure of the transplanted heart: diagnostic and therapeutic challenges.

Patients with advanced heart failure can continue to experience substantial cardiac dysfunction even after undergoing multimodal therapy with pharmacologic agents, cardiac resynchronization therapy, and ventricular assist devices. Although progress is being made in regard to the long-term implantation of rotary blood pumps, cardiac transplantation continues to be the ultimate treatment for many patients with end-stage heart failure.1 After orthotopic heart transplantation (OHT), combination immunosuppressive therapy is necessary to control the potential complications of acute cellular rejection (ACR) and antibody-mediated (humoral) rejection (AMR), and this last also frequently necessitates plasmapheresis.2 Controlling clinical episodes of acute rejection has a positive effect on the long-term prognoses of patients who undergo OHT; however, chronic cardiac rejection occurs in a substantial number of patients months to years after transplantation. Chronic rejection is characterized by coronary allograft vasculopathy, which is mediated by immunologic mechanisms that involve alloimmune and autoimmune processes in addition to many nonimmunity-related donor and recipient factors.3 Coronary allograft vasculopathy is the leading indication for repeat cardiac transplantation in some patients. Cardiogenic shock accompanying the acute rejection of a transplanted heart is an unusual but life-threatening occurrence. In this situation, mechanical circulatory support (MCS) has been recognized as an important method of short-term support while the immunotherapy is adjusted to control the acute rejection. However, the longer-term use of MCS is largely uncharted territory. In this issue of the Texas Heart Institute Journal, Caceres and colleagues from the Cedars-Sinai Heart Institute present an unusual and dramatic case in which a staged approach to MCS for severe post-transplant rejection with cardiogenic shock was followed by recovered allograft function.4 The patient, a 48-year-old woman with postpartum dilated cardiomyopathy, had undergone OHT 7 months previously. One month after medication side effects necessitated adjustment of the patient's immunosuppressive regimen, she presented with symptoms of cardiac dysfunction that evolved into biventricular failure. Despite readjustment of the immunotherapy, the cardiac failure progressed to severe cardiac decompensation. This led to the implementation of sequential MCS, consisting first of intra-aortic balloon pump placement, then emergent extracorporeal membrane oxygenation (ECMO), and finally the implantation of a biventricular assist device (bi-VAD, Thoratec Corporation; Pleasanton, Calif). Despite 10 days of ECMO and pharmacologic therapy, the patient's left ventricular ejection fraction (LVEF) declined to 0.10. After 5 weeks of bi-VAD support, the patient had normal right ventricular function and an LVEF of 0.60. At that point, the bi-VAD was successfully explanted. No further episodes of severe acute rejection were observed upon one-year follow-up. Several challenging clinical decisions enabled the successful management of this patient's case. Early in the episode, the patient exhibited clinical features of acute cardiac failure, but an endomyocardial biopsy specimen showed only mild (grade 1R) ACR. Nevertheless, a clinical diagnosis of significant acute rejection was made, and the patient's immunotherapy was adjusted. When the bi-VAD was placed, the left ventricular apical core showed severe (grade 3R) ACR without evident AMR, thereby confirming the clinical diagnosis of severe rejection. Subsequently, the biopsy results reverted to grade 0 ACR and negative for AMR. In retrospect, sampling variability could have led to underdiagnosis of the severity of ACR on the first biopsy. Alternatively, the acute event could have been initiated by AMR. The spectrum of AMR ranges from no clinical symptoms to severe cardiac decompensation.5,6 The changes in immunotherapy one month before the event also might have influenced the course of events. In their report, Caceres and colleagues present the various aspects of the clinical decisions involved in their management of the patient. They discuss the approach to sequential changes in immunotherapy in order to suppress the severe rejection. They chose ECMO as the most suitable short-term MCS because of the patient's substantial right and left ventricular failure. Listing her for repeat heart transplantation was considered but was decided against, because of the short time after the first procedure and the known poor results of early repeat OHT. They thought that a more durable form of MCS was necessary, so they implanted the Thoratec bi-VAD. This dramatic case report affirms the paramount importance of clinical observations when one interprets the results of diagnostic tests and a patient's responses to therapy. The report also illustrates how the multiple therapeutic methods of MCS can be applied in a careful and thoughtful manner to manage a severe episode of acute rejection with cardiogenic shock in a patient who has undergone OHT. The circumstances in each such case will necessitate individualized decision-making to improve the patient's prospects of survival.