Ashwin K. Ravichandran

Hemolysis in left ventricular assist device: A retrospective analysis of outcomes

BACKGROUND Hemolysis is becoming increasingly recognized as a major complication of left ventricular assist device (LVAD) support. Data regarding risk factors, prevalence, and outcomes are limited. To better define the characteristics and prognosis of hemolysis, we present a retrospective case-control study of LVAD patients in our institution. METHODS A detailed record review was conducted of 18 patients supported with the HeartMate II (HMII; Thoratec Corp, Pleasanton, CA) who were diagnosed with hemolysis, and their data were compared with 82 patients who received an LVAD implant during the same period who did not develop hemolysis. Patients were excluded if they did not survive hospitalization at the time of LVAD implantation. The primary end points of this analysis were time to death and time to first hospitalization. RESULTS Of 100 total patients, 18 HMII patients (18%) were diagnosed with hemolysis. Those with hemolysis were younger, had significantly higher lactate dehydrogenase and bilirubin levels, lower international normalized ratio, and no difference in cannula velocities by transthoracic echocardiography. Patient survival in the hemolysis group was markedly decreased at 1 year (38.9% vs 89.3%, p < 0.001), but no differences in hospitalization (p = 0.57) were observed. Partial to complete thrombosis was noted in all of the pumps at explant. CONCLUSIONS These findings demonstrate that hemolysis is associated with high mortality, likely serving as a marker of pump thrombosis. Elevated lactate dehydrogenase and bilirubin levels are important indicators for hemolysis, and lower international normalized ratio may pre-dispose for this worrisome condition. Diagnosis should prompt clinicians to consider pump exchange or explant, listing for transplantation, or intensifying anti-coagulation.

Rituximab is associated with improved survival in cardiac allograft patients with antibody-mediated rejection: a single center review

Antibody‐mediated rejection (AMR) after cardiac transplantation is associated with significant mortality, and the optimal treatment of this condition is poorly defined. Rituximab has been used successfully for the treatment for antibody‐mediated diseases; however, its role in AMR is unclear. We review our experience with rituximab in patients with cardiac allograft AMR. We conducted a retrospective analysis of cardiac transplant patients with a diagnosis of AMR from 2001 to 2011. Inclusion criteria were clinical suspicion of rejection with the presence of C4d complement staining on endomyocardial biopsy and the absence of cellular rejection of grade 2R or greater. Patients were divided into Rituximab and NoRituximab groups. The primary endpoint was all‐cause mortality. Secondary endpoints were infection, change in ejection fraction (EF), and rehospitalization. Thirty‐three patients met inclusion criteria, of whom 13 received rituximab and 20 did not. Baseline characteristics were similar between groups. Kaplan–Meier curves for a three‐yr follow‐up period demonstrate improved survival in the Rituximab group (p = 0.0089). There were no differences in secondary endpoints. We found that rituximab therapy was associated with improved survival in cardiac allograft AMR. Further prospective, randomized studies in larger patient populations are needed to confirm this finding and to define ideal timing for rituximab administration.

Antibody-mediated rejection of the heart in the setting of autoimmune demyelinating polyneuropathy: a case report and review of the literature.

Background. Antibody-mediated rejection (AMR) is caused by the production of donor-specific antibodies (DSA) which lead to allograft injury in part via complement activation. The inflammatory demyelinating polyneuropathies (IDP) are inflammatory disorders of the nervous system, involving both cellular and humoral immune mechanisms directed against myelin. Case Report. A 58-year-old man five years after heart transplant presented with progressive dyspnea, imbalance, dysphagia, and weakness. Nerve conduction studies and electromyogram were consistent with IDP. Plasmapheresis and high-dose steroids resulted in improvement in neurologic symptoms. Within two weeks, he was readmitted with anasarca and acute renal failure, requiring intravenous furosemide and inotropic support. Echocardiogram and right heart catheterization revealed reduced cardiac function and elevated filling pressures. DSA was positive against HLA DR53, and endomyocardial biopsy revealed grade 1R chronic inflammation, with strong capillary endothelial immunostaining for C4d. Plasmapheresis and intravenous immunoglobulin (IVIG) were initiated. His anasarca and renal failure subsequently resolved, echocardiogram showed improved function off inotropes, and anti-DR53 MFI was reduced by 57%. Conclusions. This is an example of a single immune-mediated process causing concurrent IDP and AMR. The improvement in cardiac function and neurologic symptoms with plasmapheresis, IVIG, and high-dose steroids argues for a unifying antibody-mediated mechanism.