Assessment of Temporary Warfarin Reversal in Patients With Left Ventricular Assist Devices: the KVAD Study.

BACKGROUND: Patients with left ventricular assist devices (LVADs) require interruption of warfarin for invasive procedures, but parenteral bridging is associated with many complications. Four-factor prothrombin complex concentrate (4F-PCC) can temporarily restore hemostasis in patients undergoing anticoagulation with warfarin. OBJECTIVES: This pilot study evaluated the strategy of using variable-dose 4F-PCC to immediately and temporarily reverse warfarin before invasive procedures without holding warfarin in patients with LVADs. The duration of effect of 4F-PCC on factor levels and time to reestablish therapeutic anticoagulation post procedure were assessed. METHODS: Adult patients with LVADs and planned invasive procedures were enrolled from a single center. Warfarin was continued uninterrupted. The 4F-PCC dose administered immediately pre-procedure was based on study protocol. International normalized ratio (INR)- and vitamin K-dependent factor levels were collected before and during the 48 hours after 4F-PCC administration. The use of parenteral bridging, International Society for Thrombosis and Haemostasis major and clinically relevant nonmajor bleeding (CRNMB) and thromboembolic events at 7 and 30 days were collected. RESULTS: In 21 episodes of 4F-PCC reversal, median baseline INR was 2.7 (IQR 2.2-3.2). The median dosage of 4F-PCC administered was 1794 units (IQR 1536-2130). At 24 and 48 hours post 4F-PCC administration, median INRs were 1.8 (IQR 1.7-2.0) and 2.0 (IQR 1.9-2.4). Two patients required postoperative bridging. One patient experienced major bleeding within 72 hours, and 2 experienced CRNMB within 30 days. There were no thromboembolic events. Baseline and post 4F-PCC vitamin K-dependent factor levels corresponded with changes in INR values. The median time to achieve therapeutic INR post-procedure was 2.5 days (IQR, 1-4). CONCLUSION: Administration of 4F-PCC for temporary reversal of warfarin for invasive procedures in patients with LVADs allowed for continued warfarin dosing with minimal use of post-intervention bridging, limited bleeding and no thromboembolic events.

The impact of statin therapy on neurological events following left ventricular assist system implantation in advanced heart failure.

BACKGROUND: Stroke is a leading cause of disability and death in advanced heart failure patients supported with a continuous-flow left ventricular assist system (CF-LVAS). Statins (HMG-CoA reductase inhibitors) reduce the risk of major cardiovascular and neurological events such as stroke, but their impact has not been evaluated in patients implanted with a CF-LVAS. We sought to explore the association between use of statin therapy and subsequent occurrence of neurological events, particularly stroke, following CF-LVAS implantation. METHODS: We performed a single center, retrospective, observational cohort study in 200 consecutive adults implanted with a durable CF-LVAS over a 10-year period (2008-2018). We compared patients according to statin use following pump implantation, stratified by an exploratory analysis of pump type (HeartMate II, HeartWare HVAD, and HeartMate 3 [HM3] LVAS). RESULTS: Overall, 24% of CF-LVAS recipients developed at least 1 neurological event, at a rate of 0.11 events per patient-year (EPPY) among those prescribed statins and 0.22 EPPY among non-users (age-adjusted hazard ratio [HR] 0.46; 95% confidence interval [CI],0.24-0.88; p = 0.019). In the cohort without the HM3 pump, ischemic strokes were 62% lower among statin users (0.05 versus 0.12 EPPY for non-users; age-adjusted HR, 0.38; 95% CI, 0.15-0.99; p = 0.048). The risk of ischemic stroke did not differ significantly when HM3 recipients were included in the analysis (age-adjusted HR, 0.51; 95% CI, 0.22-1.21; p = 0.13). However, ischemic stroke rate in HM3 LVAS recipients was similar to the rate in statin users who received a non-HM3 LVAS (0.06 and 0.05 EPPY, respectively). Rates of hemorrhagic stroke and other safety end points were not significantly different according to statin use. CONCLUSION: Statin prescription following CF-LVAS is associated with lower rates of neurological events, driven predominantly by a reduction in ischemic strokes. These findings suggest that most patients with a pre-existing indication for statin therapy may continue using statins following CF-LVAS in an effort to decrease the incidence of ischemic stroke.

Mobile Geolocation Technology to Improve Multidisciplinary Care of Patients With Ventricular Assist Devices: A Feasibility Study.

We evaluated the feasibility of a mobile phone-based geolocation technology in patients with ventricular assist devices (VAD). We prospectively enrolled VAD patients with a smartphone for 6 months. A proprietary mobile technology platform (Position Health, Reading, MA) was downloaded onto Apple or Android smartphones. When a patient entered an emergency department, the app was activated and a "ping" with patient location and contact information was sent to our VAD team pager. Fifty-four patients were approached, and 21 were enrolled. The primary reason for nonenrollment was lack of smartphone (46%). The technology was active for 3780 patient-days and activated on 4 occasions, all cases in which patients were inside a hospital but not seeking emergency care. When surveyed at 3 and 6 months, 90% and 100% of patients, respectively, reported the app remained active on their phones; 14 of 18 (78%) reported the app was helpful and gave them additional reassurance. Implementing this technology for VAD patients was feasible and accepted by patients and providers, but a larger study is needed to demonstrate an impact on care delivery.

Development of Multidisciplinary Anticoagulation Management Guidelines for Patients Receiving Durable Mechanical Circulatory Support.

Patients receiving durable mechanical circulatory support (MCS) require life-long anticoagulation with a vitamin K antagonist (VKA). Due to alternations in hemostasis, concomitant therapy with antiplatelet agents and critical illness, they are at increased risk of thromboembolic and bleeding complications compared with the general population managed on VKAs. To prevent thrombotic events, current guidelines recommend that patients with MCS receive long-term anticoagulation with a VKA to maintain a target international normalized ratio (INR) as specified by device manufacturers, but limited data exist regarding specific routine management of anticoagulation therapy and its potential complications. To optimize anticoagulation management and minimize risk in these patients, we have centralized anticoagulation management in a collaborative approach between the inpatient hemostatic and antithrombotic (HAT) stewardship service and between ambulatory anticoagulation management service (AMS) and the advanced heart disease team. Patients are followed by these three services beginning when the device is implanted and extending the duration that patients have the device. The teams include multiple clinicians from cardiac surgery, cardiology, hematology, pharmacy, nursing, case management, nutrition, and psychiatry, therefore, in order to standardize practice among clinicians without compromising patient centered decision making, we assembled an interdisciplinary team to create multiple treatment guidelines. In addition to a centralized and collaborative approach, our guidelines ensure seamless transitions of care between the inpatient and outpatient settings. We believe our approach has demontrated a positive improvement in the care of these challenging patients. In this article, we present our comprehensive centralized anticoagulation management approach for patients with left ventricular assist systems (LVAS).

Development of an Outpatient Guideline for Optimal Anticoagulation Bridging in Patients With Durable Mechanical Circulatory Support.

Patients with durable mechanical circulatory support are at increased risk of thromboembolic and bleeding complications. Current guidelines recommend that these patients receive chronic anticoagulation with warfarin to maintain a target international normalized ratio (INR) as specified by device manufacturers. Limited data exist regarding management of subtherapeutic INRs in this setting. To standardize clinical practice at our institution, we assembled a multidisciplinary task force including members from various specialties to develop a guideline for managing subtherapeutic INRs that incorporates published data and expert opinion. In this article, we present our clinical practice guideline as a decision support tool to aid clinicians in developing a consistent strategy for managing subtherapeutic INRs and for safely bridging anticoagulation in patients receiving mechanical circulatory support.

Left ventricular dimension decrement index early after axial flow assist device implantation: A novel risk marker for late pump thrombosis.

BACKGROUND: It is increasingly recognized that pump thrombosis most likely represents the end stage of a complex interaction between the patient-pump interface. We hypothesized that early patient/pump mismatch, as manifested by suboptimal left ventricular (LV) unloading early after left ventricular assist device (LVAD) implantation, may be a harbinger of increased risk for later LVAD thrombosis. METHODS: In 64 patients (59 ± 11 years old, 78% men, 44% destination therapy) discharged alive without thrombosis or other device malfunction after first HeartMate II LVAD implantation (between January 2011 and June 2014), LV dimensions in end diastole (LVIDd) and end systole (LVIDs) were compared between pre-implant and optimal set speed pre-discharge echocardiography. LV dimension decrement indices (pre-implant dimension - optimal set speed dimension ÷ pre-implant dimension × 100) for LVIDd [LVIDdDI] and LVIDs [LVIDsDI] were calculated. RESULTS: The incidence of pump thrombosis was 0.06 per patient year (n = 18, median time 8 [interquartile range 2, 17] months). Baseline characteristics including pre-operative LVIDd and LVIDs were similar between LVAD thrombosis and no thrombosis groups. After ventricular assist device implantation, set speed and other ramp parameters did not differ between groups. However, LVIDdDI (19 ± 13% vs 25 ± 11%, p = 0.04) and LVIDsDI (16 ± 16% vs 27 ± 13%, p = 0.008) were significantly lower in patients with later pump thrombosis. A cutoff value of ≤15% using receiver operating characteristic curve analysis was 83% sensitive for LVIDdDI and LVIDsDI for predicting pump thrombosis. Patients with LVIDdDI of >15% vs ≤15% were significantly more likely to be free of pump thrombosis over a median follow-up period of 15 (interquartile range 9, 26) months (log-rank test, p = 0.045). CONCLUSIONS: LV dimension decrement index at optimized speed setting on pre-discharge echocardiography is associated with LVAD thrombosis.