ABSTRACT: Heart transplant recipients who experience humoral rejection are at risk for hemodynamic instability. We report a case of a 64-year-old male with cardiogenic shock due to allograft rejection requiring mechanical support while undergoing intense immunosuppression. He underwent implantation of a micro-axial endovascular pump (Impella). To our knowledge, this is the first reported case of successful Impella device deployment as a bridge-to-recovery strategy. J INVASIVE CARDIOL 2010;22:E37–E39 Acute allograft rejection is associated with increased morbidity and mortality in heart transplant recipients. Cell-mediated rejection is a more common form of rejection, and antibody-mediated rejection is typically a more severe form. Humoral rejection (HR) results in hemodynamic instability in 47% of patients with a mortality rate of approximately 14%.1 Patients with late HR are more likely to have a preexisting infectious illness or malignancy, and lower ejection fraction when compared with those with early HR.1,2 The optimal therapy in HR is not well defined, but currently accepted practice includes plasmapheresis in combination with intravenous (IV) corticosteroids and immune globulin (IVIG).3 The Impella Recover LP 2.5 (Abiomed, Aachen, Germany) is a percutaneous micro-axial left ventricular mechanical assist device. It has a maximum diameter of 4 mm (13 Fr) at the body of the pump and is powered by an encapsulated electric motor drive connected to an external control unit. Utilizing the Archimedes principle, the pump draws blood from the left ventricle through an inflow cannula and delivers nonpulsatile flow up to 2.5 L/min (50,000 rpm) to the ascending aorta through an outflow port. The beneficial hemodynamic effects include a decrease in mean pulmonary capillary wedge pressure (PCWP),4 as well as an increase in aortic and coronary perfusion pressures5 and improved cardiac index.6 The Impella has been used for temporary hemodynamic support in patients with cardiogenic shock complicating acute myocardial infarction (AMI), after heart surgery and in those undergoing high-risk percutaneous intervention with severely depressed systolic function.6–9 We report a case of Impella implantation as a bridge to recovery in a 64-year-old heart transplant recipient with cardiogenic shock due to an episode of late humoral rejection. Case Report. A 64-year-old male with a history of two orthotopic heart transplantations in 1998 and 2005 presented following 3 months of worsening dyspnea. During a recent hospitalization, he underwent evaluation for allograft rejection. Endomyocardial biopsy revealed grade 1A rejection. Dobutamine stress echocardiography did not demonstrate inducible ischemia. Right-heart catheterization (RHC) without ionotropic support revealed reduced cardiac index (CI) (2.1 L/min/m2) and elevated PCWP (22 mmHg). The patient was treated with diuretics; he improved and was discharged home. However, he was readmitted 2 weeks later with worsening dyspnea, New York Heart Association (NYHA) Class III symptoms, hyponatremia (sodium 132 mmol/L) and elevated NT-pro-BNP (5814 pg/mL). IV diuretics were started. A multiple gated acquisition scan (MUGA) demonstrated a left ventricular ejection fraction (LVEF) of 39% and a right ventricular ejection fraction of 25%. Coronary angiography did not show significant obstructive epicardial coronary artery disease (CAD) or transplant graft coronary artery disease. RHC without inotropic support demonstrated moderate pulmonary arterial and venous hypertension: RA pressure 19 mmHg, pulmonary artery (PA) pressure 45/30 mmHg with a mean of 35 mmHg, PCWP 26 mmHg and CI (1.8 L/min/m2). An endomyocardial biopsy was performed. A presumptive diagnosis of acute cell-mediated rejection was made and IV methylprednisolone was administered. The patient improved initially, but subsequently experienced episodes of bradycardia and hypotension. On hospital day 9, the patient suffered a bradycardic arrest from which he was resuscitated. On combination of dopamine at 10 µg/kg/min and dobutamine at 19 µg/kg/min, RHC showed RA pressure of 19 mmHg, PA pressure of 45/24 mmHg, PWCP of 26 mmHg and CI 1.8 L/min/m2. The patient stabilized and a course of plasmapheresis and IVIG was started for the treatment of humoral rejection. The endomyocardial biopsy results returned showing strong C4D staining of capillaries suggestive of humoral rejection (Figure 1). There was no evidence of cell-mediated rejection (grade 1A) (Figure 2), the Allomap score was 33 and the Immuno test was 139. However, signs of secondary end-organ dysfunction persisted despite increasing IV ionotropic therapy. An intra-aortic balloon pump (IABP) was considered, but was felt to be insufficient for hemodynamic support.9 An LVAD was also considered, but given his numerous prior cardiac surgeries and our hope that immunotherapy would improve his cardiac function, we elected to percutaneously place an Impella 2.5L device. The maximum flow generated by the Impella was 2.0 L/min. After the Impella placement, the patient’s CI improved to 2.5 L/min/m2 and inotropic support was decreased over the next 40 hours. Approximately 48 hours after Impella implantation, a mechanical device failure occurred. After the device was removed and inspected, it appeared that the struts in the inlet area of the device were deformed, which was the likely cause of the device malfunction. The patient completed his plasmapheresis and IVIG regimen. He received a dose of rituximab, was subsequently weaned off all inotropic support and was discharged home on hospital day 24 with NYHA Class II congestive heart failure symptoms. His discharge medications included prednisone, cyclosporine, mycophenolate, gemfibrozil, eryhtropoietin, insulin, ramipril, furosemide, carvedilol, metolazone, omeprazole and multivitamins. Prior to discharge, his MUGA scan revealed an LVEF of 41% and improved right ventricular function to 34% from the admission value of 25%. Nine months after hospitalization, the patient’s endomyocardial biopsy showed weak C4D capillary staining (Figure 3). Coronary angiography showed new severe transplant graft CAD in all three major vessels. Discussion. In approximately 50% of cases, humoral allograft rejection results in significant hemodynamic instability.10 Recovery of myocardial function in many patients may take several days. During this period many patients may suffer from the deleterious effects of low cardiac output. The IABP can be used for circulatory support, however, its limitations include an inability to directly unload the left ventricle and a limited capacity to increase cardiac output and cardiac index by only 0.5 L/min and by 0.7 L/min/m2, respectively.9,11 The use of a percutaneous assist device such as the Impella in the setting of hemodynamically significant humoral rejection may provide the necessary support as a bridge-to-recovery, destination, or re-transplantation. Currently, there are several different devices available for such an approach. Extracorporeal membrane oxygenation (ECMO) offers temporary support in severe cardiopulmonary collapse. It is limited, however, by the need for surgery, its large cannula size and lack of direct LV unloading, and frequent ischemic limb complications. The Tandem Heart™ pVAD (Cardiac Assist Technologies, Inc., Pittsburgh, Pennsylvania,) is a left atrial-to-femoral arterial percutaneous left ventricular assist device (LVAD) that draws oxygenated blood from the left atrium and returns it via a centrifugal pump to the femoral artery. The device is able to deliver up to 4–5 L/min of cardiac output. Potential drawbacks include the need for transseptal puncture, as well as large-sized arterial cannulae (21 Fr), a high risk of limb ischemia and significant bleeding.12,13 The Impella provides less hemodynamic support with continuous flow up to only 2.5 L/min, but requires a smaller cannula size (13 Fr) and is easier to deploy. Limitations of the Impella include severe aortic regurgitation (may work insufficiently and therefore limits the benefit of the pump), the possible need for a surgical cutdown to the femoral artery and the risk of hemolysis. Additionally, the presence of significant aortic stenosis or a mechanical aortic valve are strict contraindications to Impella use.12 The device can be implemented before, during or after interventional cardiac procedures in cases of the inability to wean off cardiopulmonary bypass after heart surgery. Our patient needed temporary circulatory support to allow for the implementation of an aggressive immunosuppressive regimen. Threatened by potentially worsening LV systolic dysfunction, we felt that an IABP would not provide sufficient circulatory assistance. An ECMO or a LVAD would offer the necessary amount of support, however, these were relatively contraindicated in our patient given his history of four re-do sternotomy operations. The TandemHeart was not available at our institution at the time. Therefore, for our patient with hemodynamically significant humoral rejection, we chose the Impella device to provide necessary temporary circulatory support because of the ease of placement and the risk-to-benefit profile. In our case, the use of the Impella device provided a successful bridge-to-recovery option. This case extends the experience and application of the Impella Recover device from previously reported postoperative and post-AMI cardiogenic shock and high-risk cardiac intervention cases to temporary support in heart transplant recipients with hemodynamically significant humoral rejection as a bridge to recovery while intensive immunosuppression is administered.
From the Department of Cardiology, California Pacific Medical Center, San Francisco, California. The authors report no conflicts of interest regarding the content herein. Manuscript submitted July 27, 2009, provisional acceptance given August 3, 2009, final version accepted August 7, 2009. Address for correspondence: Anna T. Beyer, MD, Department: Cardiology, California Pacific Medical Center, 2333 Buchanan Street, 1-111, San Francisco, CA 94115. E-mail: firstname.lastname@example.org
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