Comprehensive Analysis of Stroke in the Long-Term Cohort of the MOMENTUM 3 Study

Abstract

Background: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support. Methods: MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score >3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined. Results: In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1–733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181–730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08–0.63; P =0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke). Conclusions: The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (>6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02224755.

Do we need aspirin in HeartMate 3 patients?

“…This study shows safety and efficacy of an aspirin‐free antithrombotic regimen in reducing HRAEs in patients implanted with the HM3, and further expands the results by Lim et al , suggesting the potential benefit of primary warfarin monotherapy after discharge in patients stratified according to bleeding risk scores. Our data are further corroborated by Colombo et al who recently reported a higher risk of haemorrhagic stroke in HM3 patients managed with aspirin vs. patients on oral anticoagulation alone (86% vs. 57%), and a comparable incidence of ischaemic stroke in the two groups, meaning that aspirin might exacerbate the pathophysiology of bleeding disorders in HM3 patients, and that anticoagulation alone is effective and safe in preventing these phenomena. In this perspective, the value of low‐intensity anticoagulation (INR target 1.5–1.9) and aspirin therapy, as proposed by Netuka et al in the Minimal AnticoaGulation EvaluatioN To aUgment heMocompatibility (MAGENTUM 1) study, appears less attractive to reduce HM3 HRAEs.…”

“…Indeed, this strategy did not completely blunt the incidence of recurrent bleeding episodes . Furthermore, according to Colombo et al , we cannot exclude that reduced anticoagulation levels might portend a higher risk of ischaemic stroke.…”

“…The HeartMate 3 (HM3, Abbott Laboratories, Inc., Lake Forest, IL, USA) is a fully magnetically levitated left ventricular assist device that has abated the incidence of pump thrombosis and revealed an extremely low rate of thromboembolic events . However, the occurrence of bleeding events with this cardiac pump is still an issue.…”

Assessing Cerebrovascular Hemodynamics Using Transcranial Doppler in Patients with Mechanical Circulatory Support Devices

“…Early survival after implantation is satisfactory, although at times at the expense of device‐related complications 1‐3 . Significant improvement of the hardware and implantation procedure has greatly reduced device failure 4‐6 . Neurologic adverse events continue to represent a significant challenge to the long‐term outcomes after MCS device placement 2,5,7‐11 …”

Randomized trial of a left ventricular assist device as destination therapy versus guideline‐directed medical therapy in patients with advanced heart failure. Rationale and design of the SWEdish evaluation of left Ventricular Assist Device (SweVAD) trial

“…The clinical significance of these features is a decreased risk of haemocompatibility‐related SAEs compared with its predecessor, the HMII (which consisted of an axial continuous‐flow pump with mechanical bearings), and, theoretically, a lower risk of thromboembolism than with other devices operating on similar principles. Compared with the HMII, the HM3 was associated with fewer haemocompatibility‐related events during short‐term (6 months) follow‐up and a marked reduction in the incidence of stroke in the long‐term follow‐up phase (up to 2 years) of the MOMENTUM 3 trial (odds ratio 0.23, 95% confidence interval 0.08–0.63; P = 0.01) . Implantation of an HM3 pump was the only independent predictor of a lower incidence of stroke in MOMENTUM 3, a finding of significance when it is considered that the occurrence of stroke of any type or of any functional severity was predictive of poor 2‐year clinical outcome.…”