Understanding Risk Factors for Stroke Subtypes in the ENDURANCE Trials

Purpose Stroke is one of the most devastating morbidities associated with left ventricular assist device (LVAD) support. Improved blood pressure management in LVAD patients has been shown to significantly reduce strokes, in particular hemorrhagic strokes. However, little is known regarding clinical risk factors for stroke subtypes. Methods Patients experiencing a stroke in the combined HeartWare LVAD (HVAD) cohorts of the ENDURANCE (DT) and ENDURANCE Supplemental (DT2) trials were included. Neurological events (ischemic stroke ((ICVA)), hemorrhagic stroke (HCVA) and transient ischemic attack (TIA)) occurring through 2 years were reviewed in detail and analyzed for the presence of risk factors and concurrent adverse events. Perioperative strokes were defined as occurring within 2 weeks of implant. Descriptive statistics were employed to describe these patients and events. Results A total of 604 patients received an HVAD in the DT (n=296) and DT2 (n=308) trials. Over 2 years, 178 (29%) patients experienced a neurologic event, including 104 (17%) ICVA, 67 (11%) HCVA, and 44 (7%) TIAs. Most strokes occurred in the DT study patients. Thirty (17%) patients of 178 had perioperative stroke, of which 22 were ICVA, 5 were HCVA, and 3 TIAs. Subtypes of HCVA included 34 patients with intraparenchymal hemorrhages, 12 with subarachnoid hemorrhages, 5 with subdural hematomas, and 18 with ischemic strokes with hemorrhagic conversion. Comparison of baseline characteristics revealed only a few clinical predictors of stroke: patients having an ICVA tended to have more heart failure of ischemic etiology (64%), and late ICVAs tended toward a higher prior history of stroke (18%). No baseline characteristics predicted HCVA. An event-based analysis of the 30-days before a stroke revealed that the most frequent event preceding an ICVA was bleeding (11.3%) and cardiac arrhythmias (5.3%). The most frequent event preceding a HCVA was bleeding (9.9%), sepsis (9.9%), and pump thrombosis (9.9%). TIA preceded an ICVA in five patients. Conclusion In patients with HVAD, 17% of all strokes were perioperative and overall, there were more ischemic than hemorrhagic strokes or TIAs. The most common adverse event to occur before both types of strokes was bleeding. Careful consideration of antithrombotic therapy after a bleeding episode is needed to mitigate the risk of subsequent stroke.