Intracranial Hemorrhage in Patients with Durable Mechanical Circulatory Support Devices: Institutional Review and Proposed Treatment Algorithm

Background

Spontaneous intracranial hemorrhage (ICH) is frequently managed in neurosurgery. Patients with durable mechanical circulatory support devices, including total artificial heart (TAH) and left ventricular assist device (LVAD), are often encountered in the setting of ICH. Although durable mechanical circulatory support devices have improved survival and quality of life for patients with advanced heart failure, ICH is one of the most feared complications following LVAD and TAH implantation. Owing to anticoagulation and clinically relevant acquired coagulopathies, ICH should be treated promptly by neurosurgeons and cardiac critical care providers. We provide an analysis of ICH in patients with mechanical circulatory support and propose a treatment algorithm.

Methods

We retrospectively reviewed medical records from 2013–2016 for patients with a durable mechanical circulatory device at Banner–University of Arizona Medical Center Tucson. All patients with suspected ICH underwent computed tomography scan of the brain. Anticoagulation was managed by the cardiothoracic surgeon.

Results

In 58 patients, an LVAD (n = 49), TAH (n = 10), or both (n = 1) were implanted. Both acquired von Willebrand disease and spontaneous ICH were diagnosed in 5 patients (8.6%) who underwent LVAD implantation. Seven neurosurgical procedures were performed in 2 patients. The overall mortality rate was 60%. Two patients had little or no deficits after treatment with modified Rankin Scale score of 1 and 2, respectively.

Conclusions

We propose a novel treatment algorithm to manage patients with a LVAD or TAH and ICH, implemented in a multidisciplinary manner to best avoid neurologic and cardiovascular complications.

Introduction

Spontaneous intracranial hemorrhage (ICH) in patients with coagulopathies is a frequently encountered neurosurgical diagnosis at most tertiary care centers. Management of such patients requires basic knowledge of the coagulation cascade, frequent collaboration with providers from both pharmacy and critical care for appropriate reversal of coagulopathies, and swift clinical judgments to determine if and when it is safe to surgically intervene. Patients with durable mechanical circulatory support devices, including left ventricular assist devices (LVADs) such as the HeartMate II (Thoratec Corporation, Pleasanton, California, USA) and HeartWare (HeartWare, Framingham, Massachusetts, USA), and biventricular assist devices such as the total artificial heart (TAH), comprise a relatively new population of coagulopathic patients who are increasingly encountered by neurosurgeons.

LVADs are implanted artificial hearts that have been used over the last several decades by cardiologists and cardiovascular surgeons to manage advanced systolic heart failure. The device is connected to the left ventricular apex and artificially pumps nonpulsatile blood through to the ascending aorta, bypassing the failing left ventricle (Figure 1). Initially, these devices were used as a bridge to heart transplant to aid circulation, but with advancement in durable technology and a decrease in available donors, in recent years, LVADs are being increasingly considered as a destination therapeutic option to transplant.¹ TAHs are implanted in a smaller subpopulation of patients and are generally reserved for patients with severe biventricular heart failure who cannot be treated with LVAD implantation or patients with anatomic considerations that preclude LVAD implantation.² The left and right ventricles and valves of the native heart are excised and replaced by the TAH, which is connected to the great vessels, completely replacing the ventricular system to artificially pump blood to the lungs and systemically. Together, LVADs and TAHs have effectively provided bridging therapy to heart transplantation as well as destination therapy as permanent implants.

Although durable mechanical circulatory support devices have improved both survival and quality of life in the large population of patients with advanced heart failure, they are associated with complications.³ Hemorrhage (both perioperative and delayed), right heart failure, hemolysis, thromboembolism, and device failure are known complications associated with implantation.¹ The potential for thrombosis within the pump itself and thromboembolism possibly leading to stroke are the main reasons why most of these patients require treatment with warfarin. Therefore, the risk of spontaneous hemorrhage, particularly ICH, both early after device implantation and later is significant. Management of ICH in the setting of supratherapeutic warfarin therapy is not a novel clinical scenario for neurosurgeons, as the reversal of warfarin is routinely performed with fresh frozen plasma (FFP) or prothrombin complex concentrate (PCC). However, there is further reason for hemorrhage in some patients with LVADs resulting in severe cases of ICH, making both reversal of coagulopathy and treatment of hemorrhage in these patients more difficult than expected.

The overall risk of any major hemorrhage, which most often occurs within 30 days of LVAD implantation, is approximately 50%.4, 5 Approximately 25% of patients require surgery for a hemorrhagic event. In several large studies examining outcome in patients with LVADs, ICH was diagnosed in 3%–11% of the patients.4, 5, 6 Warfarin and antiplatelet therapies contribute to the risk of device-related thrombus formation and stroke, increases the risk of hemorrhage. However, it is believed that patients with LVADs acquire an inherent coagulopathy that is not necessarily due to anticoagulation, as their risk of hemorrhage is greater than can be expected from anticoagulation alone.⁷ Acquired von Willebrand disease (AvWD) is a rare disease that was previously associated only with lymphoproliferative disorders and aortic stenosis. It is now thought to significantly contribute to the overall risk of hemorrhage in patients with LVADs.⁸

von Willebrand factor (vWF) is expressed by endothelial cells and facilitates platelet aggregation at sites of vascular injury. Furthermore, it functions as a carrier of factor VIII in the plasma and prevents its proteolytic degradation, thereby enhancing circulating levels of factor VIII and increasing its delivery to sites of vascular injury.9, 10 It is believed that high shear stress within nonpulsatile flow LVADs and narrow pulse pressure produce a conformational change in the molecule and a resultant decrease in vWF multimers that circulate in the plasma. This phenomenon occurs in most patients after LVAD implantation and contributes to gastrointestinal tract bleeding in some patients, but it is yet to be specifically analyzed in patients with ICH.8, 11, 12 Some mechanical circulatory devices, such as the TAH and some types of LVADs, function via pulsatile flow, thus mimicking more physiologic blood flow, and have been shown to be associated with lower shear stress, but these devices have not been associated with a decreased incidence of AvWD or hemorrhagic complications.¹³

At our institution, which is a large academic medical center with a high clinical volume of both heart transplant surgery and neurosurgery, ICH is one of the most feared complications following LVAD and TAH implantation. Because of necessary anticoagulation and clinically relevant acquired coagulopathies, ICH in this patient population is severe and should be treated promptly and comanaged by both neurosurgeons and the cardiac critical care team. In this article, we analyze, for the first time to our knowledge, ICH encountered in patients with mechanical circulatory support devices and propose a treatment algorithm.