Some studies have found a relatively balanced percentage of ischemic and hemorrhagic strokes [5, 6, 14]. Both Kato et al. and Katz et al. had an ischemic stroke occurrence in 80% of their study population [4, 9, 15]. In contrast, Morgan et al. and Tsiouris et al. reported a greater percentage of patients suffering from hemorrhagic stroke [2, 3]. These differences in stroke etiology may reflect the individual patient cohort and preoperative risk factors. Each patient and their individual risk profiles should be considered preoperatively in order to gear management strategy toward their inherent proclivity toward hemorrhagic or ischemic stroke as best as possible.

The incidence of embolic strokes has many possible causes. As blood travels through the artificial circulatory system, it can be expected that upon contact with foreign surface material platelets and the coagulation cascade may become activated. Goldstein et al. (2013) describe blood-surface contact, platelet activation due to shear stress, and thrombus formation at cannulation or migrated cannula sites as potential causes for thrombus formation [16]. Endothelial cell adherence and activation of coagulation system (such as tissue factor VII) also can contribute to the development of coagulopathy. These factors as a function of the unique VAD position and its inherent functionality and interaction with blood cells and tissue sites can all predispose the VAD patient to development of thrombus and ischemic stroke.

Thus, the inherent thrombogenicity of the device will have an independent effect on the risk profile of a particular patient. The HMII is reported to be less thrombogenic than the previous generation HMI. Thromboembolic events may occur in 25% of patients on LVAD support [17]. Each available device would carry its own set of thrombogenic risk due to the nature of the materials used in its manufacture. However, as most large trials are conducted with the use of the HMII, not enough studies are available to compare adequately due to the large differences in patient enrollment numbers and power of the studies. Several emulation methods and models are being design to test and evaluate the thrombogenic potential and thromboresistance of devices [18–20]. The ability to calculate or accurately numerically quantify the thrombogenicity of any one device remains theoretical as such effects would present an enormous challenge that would require not only a superb ability to control for confounding factors but would also remain a qualitative assessment of one device in comparison to its peers, and it may therefore be impossible to isolate the intrinsic thrombogenic effect and stroke risk profile of any one particular device in a quantitative, predictive manner.

In comparing pulsatile flow devices with continuous flow devices, Yuan et al. demonstrated that the incidence of stroke was not significantly higher for one patient cohort in comparison with the other; however, comparing the pulsatile HMI with the continuous flow HMII, the median postoperative day of stroke occurrence was 19 days compared to 363 days for the HMII device [21]. In demonstrating a better outcome for later-occurring strokes with the HMII device, one can predict that the time frame in which the stroke occurs is likely to have a significant influence on patient recovery and long-term prognosis rather than only the device flow itself.

Many factors may play a role in the development of hemorrhagic stroke in LVAD patients. In addition to the inherent risks of bleeding secondary to cardiopulmonary bypass for on-pump VAD placement, VAD physiology itself can pose increased risk for bleeding and as such stroke. Acquired von Willebrand syndrome can develop in the post-implant period due to the shearing forces created on platelets as they pass through the pump structure; these forces can cause the platelet surfaces to be disrupted, destroy cells, and lead to a decreased amount of available von Willebrand factor, a platelet factor that contributes to the adherence of platelets to disrupted endothelial surfaces. Reduced von Willebrand factor leads to pathologic bleeding and may play a role in the development of hemorrhagic strokes.

The pathogenesis of hemorrhagic stroke in the LVAD patient has not been fully elucidated. Of course, the occurrence of supratherapeutic anticoagulation leading to adverse cerebral bleeding events is a readily discernible cause; however, other cases of its etiology may not be as clear. Aggarwal et al. (2012) describe the rate of intracranial hemorrhage in LVAD patients to 13–14% and describe the current hypotheses to be broken down into three categories. In the first category, hemorrhagic transformation from angiogenesis and reperfusion at the site of a previous infarct is attributed to the migration of prior emboli fragments [22]. The second hypothesis relates to the advent of rupture and bleeding from bloodstream infection seeding that leads to formation of cerebral mycotic aneurysms. Trachtenberg et al. describes the incidence of mycotic aneurysm formation in patient who suffered from hemorrhagic stroke and bacteremia likening the pathology to that of cererbrovascular accidents (CVA) related to embolization and bacterial seeding that occur in patients with infective endocarditis [5]. Aggarwal et al. also purports that infectious vasculitis can also weaken microvasculature in the brain leading to bleeding [22]. Hence, the main themes surrounding the postulations as to the mechanism of hemorrhagic stroke development can be divided into etiologies based on anticoagulation level abnormalities, consequences of pump characteristics, hemorrhagic transformation of ischemic stroke, and the predisposition of infection to increase susceptibility to intracranial hemorrhage.

LVAD studies that have examined the sidedness of strokes suffered by LVAD study participants have showed a greater incidence of right-sided over left-sided strokes. In the Kato et al. study, 58.7% of strokes occurred in the right hemisphere as compared to 28.2% in the left [4]. With no difference in patient anticoagulation profiles, 59.3% of right-sided strokes occurred in patients with either sepsis or LVAD-related infections as compared to 23.1% of those who suffered left-sided strokes. Harvey et al. study concurs with this analysis and gives support to the increased incidence of right-sided strokes and its correlation with patients afflicted by concurrent infection at the time of stroke [6]. The introduction of an LVAD and its related postoperative position of the outflow cannula works along with anatomical positioning of the innominate such that embolic fragments are more frequently directed into the right-sided cerebral vasculature.

Adverse neurological events can have a significant effect on patient mortality, future ability to receive cardiac transplant, and prolong the patient recovery period.

Mortality after stroke is increased twofold and is reported to be as high as 20–25% within 30 days and 30–43% at 1 year. [2, 6, 23] Survival rate at 24 months is reported to be 53.9% in contrast to 74.7% in stroke-free patients [6]. Of those surviving after stroke, 67% remained on ongoing mechanical support [2]. In particular, hemorrhagic stroke and the need for tracheostomy are significant predictors of patient survival [3]. Although some studies have found no significant differences in mortality related to ischemic versus hemorrhagic stroke [6], the mortality rate is reported to be increased 1.5× after hemorrhagic stroke and has been reported with 100% mortality [5–22]. Patient mortality is significantly augmented after the advent of a stroke with evidence for an even more devastating patient course after occurrence of a hemorrhagic subtype.

Aside from effects on patient survival and mortality, patients suffering from strokes on mechanical circulatory support can experience significant quality of life changes or rehabilitation setbacks. In addition, strokes are responsible for upward of 8% of hospital readmissions after implantation [24]. Nearly 56% of patients surviving stroke spend time in a skilled nursing or rehabilitation facility [23]. Stroke is associated with significant decreased rate of nearly threefold less cardiac transplantations per person-year [6].