Douglas L. Jennings

Thrombosis in Continuous‐Flow Left Ventricular Assist Devices: Pathophysiology, Prevention, and Pharmacologic Management

Continuous‐flow left ventricular assist devices reduce short‐term mortality and improve quality of life in patients with end‐stage heart failure. Unfortunately, device‐related complications remain common, with many patients experiencing adverse events within the first year. New literature suggests that rates of device‐related thrombosis may be increasing since 2011, which is particularly troublesome given that this pathology can result in a disabling stroke, organ damage, and death. In 2013, a group of practitioners in the field of mechanical circulatory support published a treatment algorithm based on their expert opinion. However, a comprehensive review of the pharmacotherapy of this condition is lacking. A search of the literature revealed 20 separate publications of case reports or case series describing outcomes associated with the use of drug therapy for suspected pump thrombosis. Each of these experiences was limited by small sample size, nonrandomized treatment allocation, and nonstandardized medication dosing. Data describing the outcomes of surgical versus medical management of device thrombosis are also sparse, with only three published reports identified. Based on the review of this limited literature, surgical management appears to be the preferred treatment modality, especially in those with organ hypoperfusion or hemodynamic instability. In patients ineligible for surgery, pharmacotherapy options remain limited. Use of all drug classes described in the literature for the HeartMate II device—fibrinolytics, glycoprotein IIb/IIIa inhibitors, and direct thrombin inhibitors—was hindered by either marginal efficacy or bleeding. Based on historical experience with unfractionated heparin in patients under HeartMate II support, we recommend this agent as a possible option for those with suspected pump thrombosis in lieu of surgical device exchange. For the HeartWare HVAD, limited data suggest that direct intraventricular administration of alteplase may be an acceptable treatment alternative. Additional research is clearly needed to further delineate the role of pharmacotherapy and to identify the optimal agent for managing this potentially life‐threatening condition.

Clinical Outcomes Associated With Chronic Antimicrobial Suppression Therapy in Patients With Continuous-Flow Left Ventricular Assist Devices

This retrospective cohort study evaluates the effect of chronic antimicrobial suppression (CAS) therapy on clinical outcomes in patients with continuous-flow left ventricular assist devices (CF-LVADs) and a history of device-related infection. Patients with CF-LVAD implantation between January 2008 and August 2011 who received systemic CAS after index antibiotic treatment of a device-related infection were included. Chronic suppression was defined as continuation of antibiotics for longer than 6 weeks after the index infection. Standard International Society for Heart and Lung Transplantation definitions were used. The primary outcome is failure of CAS, defined as a clinical deterioration resulting in the need for transition from oral to intravenous (IV) therapy or a need to change to a different IV antibiotic, elevation to status 1A on the transplant list as a result of ongoing infection, or device/driveline exchange. Of 140 patients screened, 16 patients were included (69% male, 63% African American, median age 52 years). The driveline was the most common site of infection (69%). Organisms isolated included Gram-positive cocci (n = 7), Gram-negative bacilli (n = 10), and Candida (n = 1). Oral trimethoprim/sulfamethoxazole treatment was most commonly used for suppression (37.5%). Failure of CAS occurred in 5/16 (31%) patients after a mean time of 175 days on therapy (range 10-598). The majority of failures (60%) required device exchanges. Side effects of nausea, vomiting, or diarrhea were reported in three patients; all required changes in oral suppression regimen. Clostridium difficile infection was noted in two patients. These results, which must be confirmed by a larger analysis, suggest that one-third of CF-LVAD patients may develop recurrent infections while on CAS therapy.

Safety of anticoagulation reversal in patients supported with continuous-flow left ventricular assist devices.

The purpose of this study was to characterize the potential thromboembolic risk associated with the reversal of warfarin-based anticoagulation in patients with continuous-flow left ventricular assist devices (CF-LVADs). All patients implanted with a CF-LVAD between January 1, 2008, and August 1, 2012, at our institution were screened, and those who received anticoagulation reversal during an inpatient admission were enrolled. The primary outcome is the incidence of thrombotic events, including stroke, device thrombosis, or venous thromboembolism within 30 days of anticoagulation reversal. Of the 122 patients screened, 25 patients experienced 38 anticoagulation reversal events. All patients received vitamin K at a mean dose of 10 ± 8 mg, while 60% of patients received fresh frozen plasma. Only two patients received prothombin complex concentration and three patients received activated factor VII. The rate of thromboembolism within 30 days of attempted reversal was 2.6% (1/38). This patient developed an ischemic stroke after reversal with a high dose of activated factor VII for an acute intracranial bleed. The mortality rate within 30 days of reversal was 20% (5/25), with three of these deaths associated with acute intracranial hemorrhage. Anticoagulation reversal may be safely attempted in selected patients under CF-LVAD support.

Effective Anticoagulation for a Percutaneous Ventricular Assist Device Using a Heparin-Based Purge Solution

Objective: To report on a series of patients who were successfully anticoagulated with a novel protocol including a heparin-based purge solution. Case Summary: Four patients were supported for a total of 300 hours on the new Impella anticoagulation protocol, which was based on our current nurse-driven cardiology heparin protocol. Three patients were in cardiogenic shock after acute myocardial infarction, and 1 patient was in shock from severe aortic valvular disease. Despite prolonged cardiogenic shock, none of the patients developed significant renal or liver dysfunction while on device support. All 4 patients survived to hospital discharge, and there were no significant bleeding or thromboembolic events. Furthermore, there were no device malfunctions or clotting events within with pump motors. Despite frequent changes to the purge solution flow rate by the Automated Impella Controller, the patients in our cohort had relatively stable activated partial thromboplastin time values. Discussion: Our novel anticoagulation protocol, which incorporates the heparin included in the purge solution into the total hourly heparin dosage, was successful in the first cohort of patients receiving extended Impella support for cardiogenic shock. Our case series also highlights that the Automated Impella Controller makes frequent adjustments to the purge solution, which depending on the heparin concentration, can result in significant fluctuations in the patient’s total hourly heparin dosage. Furthermore, balancing the heparin in the purge solution with the intravenous heparin is important to ensuring adequate anticoagulation in patients supported by the Impella devices in the intensive care unit. Conclusions: Development of a standardized anticoagulation protocol for the Impella device that factors the heparin-based purge into the total heparin dosage and makes appropriate adjustments based on the fluctuating rate of the purge solution can provide effective anticoagulation to patients receiving extended circulatory support from this device.

Dosing of vancomycin in patients with continuous-flow left ventricular assist devices: a clinical pharmacokinetic analysis.

Purpose To describe the pharmacokinetics of vancomycin in patients with continuous-flow left ventricular assist devices (CF-LVADs). Methods Eligible patients were ≥18 years old, implanted with a Heart Mate II CF-LVAD during January 2008-April 2012, and treated with vancomycin ≥48 hours for infection. Key exclusion criteria were unstable renal function, acute heart failure exacerbation, hemodynamic instability, and recent surgery. First-order elimination rate constant (Ke) and volume of distribution (Vd) were estimated using ideal (IBW), adjusted (AdjBW), actual (ABW), and fixed body weights. Estimated parameters were compared with measured pharmacokinetic parameters, which were calculated from steady state peak and trough vancomycin levels using one-compartment model equations. Results Twelve patients were included (age 44.9 ± 15 years, 91.7% male, 58.3% obese, CLcr 79.2 ± 27 mL · min-1). Common treatment indications were health-care associated pneumonia (41.7%), driveline infection (25%), and sepsis (16.7%). All methods of predicting Ke provided overestimates (p<0.05), ranging from 47 to 79%, depending on body habitus. Methods of predicting Vd using ABW in obese patients yielded overestimates of 74.5% (p<0.05), where IBW predictive Vd equations provided accurate assessments regardless of body habitus. Conclusions General population methods may not accurately estimate the pharmacokinetic parameters of vancomycin for compensated heart failure patients implanted with CF-LVADs.

Impact of Platelet Functional Assays on the Cost of Treating Suspected Heparin-Induced Thrombocytopenia

Objectives: To investigate the potential cost savings of using functional platelet assays to confirm the diagnosis of heparin-induced thrombocytopenia (HIT). Methods: This was a single-center study conducted in the United States. We performed a retrospective cost of illness analysis of suspected HIT, comparing patients with the serotonin release assay (SRA) ordered as part of their diagnostic evaluation to those who did not. The primary clinical end point was a composite of mortality and major bleed. Results: A total of 147 patients met the study’s inclusion criteria. An SRA was ordered in 53 patients of whom 17% were positive. Overall, SRA use did not reduce the composite primary clinical end point (32.1% vs 33%, P = .911). Also, there was no difference in the total cost of hospital stay (US

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84781.1 vs US

Clinical outcomes with beta-blockers after myocardial infarction: finding the right patient and the right regimen.

78534.4, P = .409) nor in the direct medical costs related to HIT management (US

Epidemiology and Outcomes Associated With Anemia During Long-Term Support With Continuous-Flow Left Ventricular Assist Devices

7473.5 vs US

Safety of Anticoagulation Reversal in Patients Supported With Continuous-Flow Left-Ventricular Assist Devices

8402.4, P = .393). Early ordering of the SRA (within 48 hours) was associated with shorter length of stay (20 vs 27 days, P = .029) but without a difference in cost of treatment. Conclusion: The use of SRA did not reduce the costs or improve clinical outcomes in patients with suspected HIT.