Minimum inhibitory concentration changes in relapsed left ventricular assist device driveline infections.

Driveline infection is the most common infectious complication in patients with left ventricular assist devices. Minimum inhibitory concentration changes are not well described in relapsed driveline infections. This retrospective descriptive epidemiology study of patients with left ventricular assist device implantation between January 1, 2013, and August 1, 2017, who developed driveline infection with positive cultures aimed to describe minimum inhibitory concentration changes. Of the 330 patients underwent left ventricular assist device implantation, 30 (9%) met criteria for driveline infection. Median duration of follow-up was 26 months (interquartile range 16, 39) and time to first driveline infection was 171 days (interquartile range 83, 403). There were 74 driveline infections: 40 new and 34 relapsed. Staphylococcus aureus was most common in new and relapsed driveline infection. Thirteen patients comprised the 34 relapsed infections, 9 of which experienced a minimum inhibitory concentration change. Median time to first minimum inhibitory concentration change was 56 days (interquartile range 36-88), and type of minimum inhibitory concentration change was an increase in five cases, decrease in two cases, and both increase and decrease in two cases. Minimum inhibitory concentration changes did not result in resistance in S. aureus but did in Pseudomonas aeruginosa and Mycobacterium fortuitum relapsed driveline infection. Time to first relapse from initial infection was longer in those who received suppressive therapy, 60 days versus 83 days, p = 0.047. Relapsed driveline infections were most common with S. aureus. Minimum inhibitory concentration changes were quite variable and may not be the major contributor to relapsed infection in gram-positive driveline infection.

Pharmacotherapeutic Management of Gastrointestinal Bleeding in Patients with Continuous-Flow Left Ventricular Assist Devices.

Continuous-flow left ventricular assist devices (CF-LVADs) have become an integral component of the management in patients with advanced heart failure, serving as destination therapy or as a bridge to heart transplantation. Despite significant advances in the design and longevity of the device, the ongoing risk for bleeding remains a significant concern. The genesis of gastrointestinal bleeding (GIB) in patients with CF-LVADs is likely multifactorial and may include components of acquired von Willebrand disease, angiodysplasia, and gastrointestinal arteriovenous malformations, as well as additional risk factors such as history of GIB and increased age. Several pharmacotherapy options have been used, but the data surrounding their overall efficacy remain sparse. The necessity for larger prospective studies is essential to further advance the management of this devastating complication. Within this review, we discuss the known pathophysiologic process of CF-LVAD-related GIB and highlight the therapeutic options discussed within the literature. In addition, we discuss potential therapeutic options based on mechanisms of action as they correlate to known pathophysiologic processes of CF-LVAD-related GIB. Finally, we provide recommendations for constructing drug therapy regimens in patients with CF-LVADs who develop GIB.

Pharmacologic Considerations in the Management of Patients Receiving Left Ventricular Percutaneous Mechanical Circulatory Support.

Percutaneous mechanical circulatory support (MCS) devices, including the intraaortic balloon pump, Impella, and TandemHeart, are often used for hemodynamic support in the setting of refractory cardiogenic shock. The thrombotic and bleeding complications associated with these devices is well recognized, and the Impella and TandemHeart devices have unique anticoagulation considerations that may influence patient outcomes. Both devices typically require use of a heparinized purge solution in combination with intravenous unfractionated heparin, thereby providing multiple sources of heparin exposure. Each device also has specific monitoring requirements and goal ranges. This review provides an overview of percutaneous MCS devices commonly used in the acute management of left ventricular failure, with an emphasis on pharmacologic considerations. We review recent evidence and guidelines and provide recommendations for appropriate use of anticoagulation during device support. Approaches to managing heparinized purge solutions, monitoring, and the utility of nonheparin anticoagulants are also provided because high-quality evidence in the literature is limited.

Inhaled Pulmonary Vasodilator Therapy for Management of Right Ventricular Dysfunction after Left Ventricular Assist Device Placement and Cardiac Transplantation.

Right ventricular failure (RVF) after cardiac transplant (CTX) or implantation of a continuous-flow left ventricular assist device (CF-LVAD) is associated with significant postoperative morbidity and mortality. A variety of modalities have been used to treat postoperative RVF, including management of volume status, intravenous inotropes and vasodilators, and right-sided mechanical support. Inhaled vasodilator agents are a unique treatment option aimed at minimizing systemic absorption by delivering therapy directly to the pulmonary vasculature. Current LVAD and CTX guidelines endorse inhaled vasodilators for managing postoperative RVF; however, no guidance is offered regarding agent selection, dosing, or administration. A review of the current literature confirms that inhaled pulmonary vasodilator agents have been shown to decrease pulmonary artery pressure when used in the perioperative period of CF-LVAD implant or CTX. However, the literature regarding the potential impact on clinical outcomes (e.g., survival or risk of developing RVF) is lacking with these medications. Based on our assessment of the literature, we suggest that when RVF occurs in the setting of a normal pulmonary vascular resistance (PVR), traditional inotropic therapy (e.g., dobutamine) should be used. Conversely, if the PVR is elevated (> 250 dynes/sec/cm5 or 3 Wood units), or the patient has other evidence of a high right ventricular afterload (i.e., a transpulmonary gradient > 12 mm Hg), then an inhaled pulmonary vasodilator would be the preferred initial pharmacologic agent. Drug selection depends largely on the institution's capacity to safely prepare and administer the medication, along with formulary considerations, such as the high costs associated with inhaled iloprost and inhaled nitric oxide.

Phenotyping Adverse Drug Reactions: Statin-Related Myotoxicity.

It is unclear the extent to which best practices for phenotyping disease states from electronic medical records (EMRs) translate to phenotyping adverse drug events. Here we use statin-induced myotoxicity as a case study to identify best practices in this area. We compared multiple phenotyping algorithms using administrative codes, laboratory measurements, and full-text keyword matching to identify statin-related myopathy from EMRs. Manual review of 300 deidentified EMRs with exposure to at least one statin, created a gold standard set of 124 cases and 176 controls. We tested algorithms using ICD-9 billing codes, laboratory measurements of creatine kinase (CK) and keyword searches of clinical notes and allergy lists. The combined keyword algorithms produced were the most accurate (PPV=86%, NPV=91%). Unlike in most disease phenotyping algorithms, addition of ICD9 codes or laboratory data did not appreciably increase algorithm accuracy. We conclude that phenotype algorithms for adverse drug events should consider text based approaches.