Evaluation of adjusted international normalized ratio goal in patients with HeartMate 3 left ventricular assist devices.

BACKGROUND: The HeartMate3 left ventricular assist device (HM3 LVAD) has shown a low incidence of thrombosis, but bleeding risk is as high as 43%. We aim to describe the impact of lower international normalization ratio (INR) goal on clinical outcomes. METHODS: In February 2019, our tertiary care institution lowered INR goal in HM3 patients from manufacturer recommendations to 1.8-2.2 and retrospectively analyzed the data. Two cohorts were compared: patients with lower INR goal upon implant (De novo) and those with subsequently lowered INR goal (Adjusted). The Adjusted group also served as its own historical control. Both groups continued aspirin 81 milligrams daily per manufacturer recommendations. The primary outcomes were incidences of bleed and thrombosis events within 12 months. Secondary outcomes included survival free of disabling stroke or reoperation to remove or replace the device and Rosendaal time in therapeutic range (TTR) over 12 months. RESULTS: Thirty-one patients were evaluated for inclusion with 26 meeting criteria. Within 12 months, incidence of bleeding events was 25% and 28.6% in the De novo and Adjusted groups, respectively. Incidence of thrombotic events within 12 months was 0% in the De novo group and 7.1% in the Adjusted group. Twelve-month survival free of disabling stroke or reoperation to remove or replace the device was higher over 12 months for patients in the De novo group (91.7% vs. 78.6%). Median 12-month TTR was 36%, which was primarily attributable to subtherapeutic deviations. CONCLUSIONS: A lower INR goal may be safe when initiated De novo following implantation of the HM3. This study informs the need for larger prospective studies.

Retrospective review of secondary prevention strategies for gastrointestinal bleeding and associated clinical outcomes in left ventricular assist device patients.

BACKGROUND: Gastrointestinal bleeding (GIB) is one of the most common bleeding complications associated with left ventricular assist devices (LVAD). Currently, there is no strong evidence or clear guidance for which secondary GIB prophylaxis strategy should be implemented after the discontinuation of aspirin. METHODS: Our single-center study describes the outcomes of 26 LVAD patients who experienced a total of 49 GIB events: these individuals were either in Group-1 (lower INR target range) or Group-2 (lower INR target plus a hemostatic agent) as the secondary prophylaxis strategy. Each GIB event was considered an independent event. Outcomes assessed were bleeding reoccurrence rates, time to next GIB, acute GIB strategies, GIB-free days, thromboembolic events, survival, coagulation, and hematologic parameters. RESULTS: GIB reoccurrence rates were not statistically different: Group-1, 9 (40.9%), versus Group-2, 15 (55.6%); p = 0.308. Danazol was utilized 81.5% of the time as the designated hemostatic agent. Additionally, no significant differences were observed with all of our secondary outcome measures for bleeding, ischemic events, or survival. CONCLUSION: While our study was not powered to assess the clinical outcomes related to survival and thromboembolic events, no discernable increased risk for ischemic events including pump thrombosis were observed. Our data suggest that a lower INR target range plus danazol does not confer any additional benefit over a lower INR target range only approach. The results of this report are hypothesis-generating and additional studies are warranted to elucidate the optimal antithrombotic strategy and role of hemostatic agents in reducing the risk of recurrent GIB events.

Comparison of Bivalirudin Versus Unfractionated Heparin for Anticoagulation in Adult Patients on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) contributes to coagulopathy, necessitating systemic anticoagulation to prevent thrombosis. Traditionally, unfractionated heparin (UFH) has been the anticoagulant of choice, however, due to many inadequacies new evidence suggests benefit with the use of direct thrombin inhibitors. This retrospective cohort sought to evaluate the safety and efficacy of bivalirudin compared to UFH in ECMO patients. Primary endpoints included incidence of bleeding and thrombosis. Percent time in therapeutic range (TR), time to achieve TR and number of dose titrations required to maintain TR were calculated to assess efficacy of institutional protocols. Overall incidence of thrombosis was low, with one event in the bivalirudin group and no events in the UFH group. No difference was found in rates of bleeding between groups (6% vs . 10%, P = 0.44). Bivalirudin yielded higher percent time in TR (86% vs. 33%, P < 0.001), faster time to TR (2 vs . 18 hr, P < 0.001) and required fewer dose adjustments to maintain TR (2 vs . 11, P < 0.001) compared to UFH. These results suggest bivalirudin and UFH are associated with similar rates of bleeding and thrombosis in patients requiring ECMO support. Our results demonstrate the favorable pharmacokinetic profile of bivalirudin, and its ability to consistently maintain TR when compared to UFH.

Evaluation of Bivalirudin as the Primary Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation for SARS-CoV-2-Associated Acute Respiratory Failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population. OBJECTIVE: The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure. METHODS: This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h. RESULTS: There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%. CONCLUSION AND RELEVANCE: In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.

Cisatracurium Continuous Infusion Versus No Neuromuscular Blockade for Acute Respiratory Distress Syndrome on Venovenous Extracorporeal Membrane Oxygenation.

The benefit of continuous infusion neuromuscular blockade concurrently with venovenous (VV) extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome who are receiving mechanical ventilation remains unclear. Adult patients with severe acute respiratory distress syndrome requiring VV ECMO were analyzed in 2 groups: continuous infusion neuromuscular blockade with cisatracurium vs no neuromuscular blockade. Similar mechanical ventilation strategies were used. The primary end point was duration of VV ECMO. This single-center, retrospective observational cohort included a total of 47 patients, 28 of whom received continuous infusion cisatracurium and 19 patients who did not receive neuromuscular blockade. There was no difference in the duration of VV ECMO in patients who received cisatracurium, 226.5 hours (interquartile range, 119-362.3) vs 187.0 hours (interquartile range, 108-374) in the group who did not receive a paralytic (P = .64). There were no differences in secondary outcomes of days in the hospital, days free of organ dysfunction, ECMO survival, or discharged alive. Among patients with severe ARDS who were managed with VV ECMO, patients who received continuous infusion cisatracurium had no difference in the duration of VV ECMO compared to the nonparalytic comparator group.

The effects of propofol on extracorporeal membrane oxygenation oxygenator exchange.

The objective of this study was to determine if propofol administration to veno-venous (VV) extracorporeal membrane oxygenation (ECMO) patients was associated with more incidents of oxygenator failure when compared to patients who did not receive propofol. This was a single center, retrospective cohort study. The primary outcome of the study is oxygenator exchanges per ECMO day in patients who received propofol versus those who did not receive propofol. Patients were 18 years or older on VV-ECMO support between January 1, 2015 and January 31, 2018. Patients were excluded if they required ECMO support for less than 48 h or greater than 21 days. There were five patients in the propofol arm that required oxygenator exchanges and seven patients in the control arm. The total number of oxygenator exchanges per ECMO day was not significantly different between groups (p = 0.50). When comparing those who required an oxygenator exchange and those who did not, there was no difference in the cumulative dose of propofol received per ECMO hour (0.64 mg/kg/h vs 0.96 mg/kg/h; p = 0.16). Propofol use in patients on VV-ECMO does not appear to increase the number of oxygenator exchanges.

Comparison of Venous Thromboembolism Prophylactic Measures Post Coronary Artery Bypass Graft Surgery.

BACKGROUND: There is considerable debate surrounding venous thromboembolism (VTE) prophylaxis in patients post coronary artery bypass grafting (CABG) procedures. The American College of Chest Physicians guidelines report weak recommendations for starting VTE prophylaxis, but provide no specific guidance regarding timing or preferred prophylactic agent. METHODS: This retrospective cohort study was designed to compare outcomes of post-cardiac surgery patients admitted to the cardiovascular intensive care unit (ICU) who received subcutaneous unfractionated heparin (UFH), with those who received subcutaneous enoxaparin for VTE prophylaxis. Between January 2013 and September 2017, 1085 patients were identified, and, after propensity score matching, 850 patients were selected for analysis. The primary outcomes were postoperative VTE and the occurrence of bleeding events up to 30 days postoperatively. Secondary outcomes included chest tube output, days mechanically ventilated, ICU length of stay, total hospital length of stay, and 30-day readmission rates. RESULTS: During the study period, rates of 2.03% for VTE events and 1.38% for bleeding events were reported in the entire cohort. After matching, the rates of VTE events (2.12% vs. 1.41%, p = 0.43) and bleeding events (1.18% vs. 0.94%, p = 1.00) were more frequent in the heparin group versus the enoxaparin group; these differences were not statistically significant. However, we did find a statistically significant increase in several secondary endpoints, including chest tube output, days mechanically ventilated, ICU length of stay, and total hospital length of stay, within the heparin cohort. Bleeding rates were similar to those previously published, despite the early initiation of VTE prophylaxis. CONCLUSIONS: We report no statistical difference in the rates of VTE or bleeding between chemical agents, but our results suggest enoxaparin may be a preferred agent over UFH.

Use of Alternative Antiplatelet Agents for Clopidogrel Hypersensitivity.

Clopidogrel is a widely used agent for secondary prevention of vascular events and is a cornerstone of dual antiplatelet therapy in patients with acute coronary syndrome (ACS) post coronary stent implantation. Hypersensitivity reactions to clopidogrel are well documented and may range from localized to systemic in presentation. This can lead to discontinuation of therapy, thus increasing the risk of vascular events. The authors have developed recommendations for potential alternative agents for the management of clopidogrel hypersensitivity reactions. Proposed strategies include treatment with an alternative P2Y12 inhibitor, cilostazol or warfarin.

Antithromboembolic Strategies for Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention.

We set out to synthesize available data on antithrombotic strategies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI), with a focus on triple antithrombotic therapy (triple therapy [TT]; dual antiplatelet therapy plus an anticoagulant) versus dual therapy (DT; one antiplatelet agent and an anticoagulant). We searched OVID MEDLINE and PubMed from January 2005 to September 2017 using the search terms oral anticoagulant, triple therapy, dual therapy, acute coronary syndrome, percutaneous coronary intervention, and atrial fibrillation (limited to randomized controlled trials, observational studies, English language, minimum 6-12 months of follow-up, minimum 100 human patients). We excluded surveys, literature reviews, articles not directly related to TT versus DT, incomplete studies, and short-term in-hospital studies. All eligible studies were reviewed to evaluate possible antithrombotic management strategies for patients with AF undergoing PCI. Extracted studies were categorized according to the specific anticoagulant (vitamin K antagonist vs. direct-acting oral anticoagulant) and P2Y12 inhibitor used. Each category review was followed by a discussion providing insight into the quality of evidence and implications for practice. We found that the risk of bleeding with TT was higher than with DT, without demonstrated added benefit of reducing major adverse cardiovascular events. TT use should be minimized in patients with high bleeding risk, and patient-specific factors should be critically analyzed to select appropriate antiplatelet and anticoagulant agents.

Safe and Effective Use of Pharmacologic and Device Therapy for Peripartum Cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is an uncommon, idiopathic complication of pregnancy associated with significant (10-30%) mortality. The disease occurs late in pregnancy or in the months following delivery, resulting in reduced systolic function and heart failure (HF) symptoms. Limited direction is provided for the management of PPCM, and the safe and effective use of medications in pregnant and breastfeeding women with PPCM presents a unique challenge. Although several HF therapies in pregnant and lactating women are supported by robust evidence, evidence to support the use of other therapies is significantly lacking. Current guidelines recommend treatment as in other forms of HF with reduced left ventricular ejection fraction (LVEF) but with consideration for the important nuances in this population as well as the unique and potential teratogenic effects of these therapies. Since most patients with PPCM recover their LVEF, the duration of therapy is currently unknown and warrants further study. We review the available literature surrounding pharmacologic and device therapy for PPCM and provide insight into managing patients with the condition.