Faculty Bibliography

BACKGROUND/UNASSIGNED:There is a lack of robust data evaluating outcomes of enoxaparin "bridge" therapy in left ventricular assist device (LVAD) patients. METHODS/UNASSIGNED:We performed a retrospective study of HeartMate II (HM II) and HeartWare HVAD recipients that received therapeutic enoxaparin as "bridge" therapy to describe bleeding and thrombotic events and compare outcomes between devices. The primary endpoint was the incidence of bleeding within 30 days of "bridge" episode. Major bleeding was defined by INTERMACS criteria. RESULTS/UNASSIGNED:= .02). We observed 3 (1%) thromboembolic events in 2 (4%) patients with an HVAD device. On multivariate analysis, the presence of a HM II device was associated with a 4-fold increased risk of bleeding. CONCLUSION/UNASSIGNED:We found the use of enoxaparin "bridge" therapy to be associated with a higher incidence of bleeding in patients with a HM II device compared with an HVAD device. Assessment of device- and patient-specific factors should be evaluated to minimize bleeding events.

Pump thrombosis remains a feared complication for patients implanted with durable left ventricular assist devices. Optimal treatment is unknown, but consists of either pharmacologic fibrinolysis or surgical pump exchange. Fibrinolysis is less invasive, but carries a significant risk of intracerebral hemorrhage. We present four cases of LVAD pump thrombosis successfully treated with a novel protocol that consists of low-dose four-factor prothrombin complex concentrate to reverse baseline INR elevation prior to alteplase administration to minimize the risk for intracerebral hemorrhage.

Study: Despite advances in design and hemocompatibility, pump thrombosis remains a significant cause of morbidity for patients implanted with durable left ventricular assist devices (LVAD). Pharmacologic fibrinolysis may be preferred as initial therapy because it obviates a surgical procedure. Yet, it historically has been associated with a significant risk of secondary intracerebral hemorrhage (ICH).
Method(s): We implemented a novel protocol to treat HVAD pump thrombosis and minimize risk of ICH that consisted of the following: initiation of a non-titrating heparin infusion at 500 units/hr; normalization of international normalized ratio (INR) by giving a flat dose of 1,000 units of four-factor prothrombin complex concentration (4F-PCC); and administration of alteplase as a 10 mg bolus followed by 40 mg given over 3 hours.
Result(s): Two patients underwent treatment with the above protocol for presumed HVAD pump thrombosis based on clinical signs of hemolysis and elevations of power on log-file analysis. One patient was 2 months from HVAD implant and the other 13 months. Both patients had subtherapeutic INR in the preceding weeks. Following administration of alteplase, log-file analysis demonstrated immediate resolution of power elevations (Fig. 1). Both patients had a subsequent rise in power requiring repeat alteplase dosing. No bleeding or thrombotic events occurred with treatment. One patient underwent heart transplant a month after treatment and is doing well; the second patient is stable on HVAD support 4 months following alteplase. Combining 4F-PCC to temporarily normalize the INR with repeat dosing of alteplase was effective at resolving HVAD pump thrombosis without bleeding complications and should be investigated further

BACKGROUND:The Impella (Abiomed) ventricular support system is a family of temporary mechanical circulatory support (MCS) devices used to treat patients with cardiogenic shock, acute cardiogenic decompensation, and for high-risk percutaneous or surgical revascularization. These devices include the percutaneously implanted 2.5/cardiac power (CP) and the surgically implanted 5.0/left direct (LD). Despite the beneficial effects and increased usage of these devices, data to assess adverse outcomes and guide clinician decision-making between the Impella CP and 5.0/LD are limited. METHODS:This is a retrospective analysis of 91 consecutive patients who required at least 24 h of Impella support, from January 1, 2015 to December 31, 2019. Groups were stratified based on either initial Impella CP or 5.0/LD placement. Clinical outcomes and in-hospital complications were compared. RESULTS:Impella CP was implanted in 66 patients (mean age: 61 ± 15 years, male 71.2%) and Impella 5.0/LD was implanted in 25 patients (mean age: 62 ± 9 years, male 84.0%). There was greater stability of device position (p = .033), less incidence of hemolysis (p < .001), and less frequent need for additional MCS (p = .001) in patients implanted with the Impella 5.0/LD compared with Impella CP in this study cohort. Patients with Impella 5.0/LD were more likely to survive from Impella and survive to discharge. CONCLUSIONS:This study suggests that for patients who require temporary MCS for more than 24 h, the Impella 5.0/LD may have a more favorable device-specific adverse profile compared with the Impella CP.

BACKGROUND:Increased utilization of hepatitis C virus (HCV)-positive donors has increased transplantation rates. However, high levels of viremia have been documented in recipients of viremic donors. There is a knowledge gap in how transient viremia may impact acute cellular rejections (ACRs). METHODS:In this study, 50 subjects received hearts from either viremic or non-viremic donors. The recipients of viremic donors were classified as nucleic acid amplification testing (NAT)+ group, and the remaining were classified as NAT-. All patients were monitored for viremia levels. Endomyocardial biopsies were performed through 180 days, evaluating the incidence of ACRs. RESULTS:A total of 50 HCV-naive recipients received hearts between 2018 and 2019. A total of 22 patients (44%) who received transplants from viremic donors developed viremia at a mean period of 7.2 ± 0.2 days. At that time, glecaprevir/pibrentasvir was initiated. In the viremia period (<56 days), 14 of 22 NAT+ recipients (64%) had ACR vs 5 of 28 NAT- group (18%) (p = 0.001). Through 180 days, 17 of 22 NAT+ recipients (77%) had a repeat rejection biopsy vs 12 of 28 NAT- recipients (43%) (p = 0.02). NAT+ biopsies demonstrated disparity of ACR distribution: negative, low-grade, and high-grade ACR in 84%, 12%, and 4%, respectively, vs 96%, 3%, and 1%, respectively, in the NAT- group (p = 0.03). The median time to first event was 26 (interquartile range [IQR]: 8-45) in the NAT+ group vs 65 (IQR: 44-84) days in the NAT-. Time to first event risk model revealed that NAT+ recipients had a significantly higher rate of ACR occurrences, adjusting for demographics (p = 0.004). CONCLUSIONS:Transient levels of viremia contributed to higher rates and severity of ACRs. Further investigation into the mechanisms of early immune activation in NAT+ recipients is required.

We conducted a retrospective review of thoracic transplant recipients (22 heart and 16 lung transplant recipients) prospectively enrolled in a single-center observational study of HCV NAT+ organ transplantation in HCV NAT- recipients. All recipients were treated with 8 weeks of glecaprevir-pibrentasvir (GP) for HCV viremia in addition to standard triple immunosuppression post-transplant. Thoracic transplant recipients of HCV NAT- organs were used as a control (24 heart and 22 lung transplant recipients). Our primary outcome was to assess the effect of GP on tacrolimus dose requirements. Secondary objectives included assessing drug interactions with common post-transplant medications, adverse effects, and the need to hold or discontinue GP therapy. The median tacrolimus concentration-to-dose (CDR) in the cohort was 184 (99-260) during GP therapy and 154 (78-304) over the first month after GP (p=0.79). Trends in median tacrolimus CDR were similar on a per-week basis and per-patient basis. In three instances, concomitant posaconazole and GP led to hyperbilirubinemia and interruption of posaconazole. GP therapy was held in one heart transplant recipient, and discontinued in another, due to unresolving hyperbilirubinemia. Utilization of GP to treat HCV viremia post-thoracic transplant is feasible and safe, but requires modifications to post-transplant pharmacotherapy and careful monitoring for adverse effects.