Review of anticoagulation considerations in extracorporeal membrane oxygenation support.

Since its first success in 1975, extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency for pulmonary and cardiopulmonary bypass. Use in adults has increased exponentially since the early 2000s, but despite thousands of international cannulations using both veno-arterial (VA) and veno-venous (VV) ECMO, there are still significant hemocompatibility-related adverse events. Current management of anticoagulation has been based on the Extracorporeal Life Support Organization guidance published in 2014 with recent updates published in 2022. Despite this guidance, there is still limited international consensus on how to manage anticoagulation in ECMO. For this review, we completed a comprehensive search of multiple electronic databases to identify studies pertaining to anticoagulation of adult patients on VV or VA-ECMO. The highest priority was given to sources that were prospective, randomized, controlled studies, but in the absence of such resources, observational studies, retrospective uncontrolled studies, and case series/reports were considered for inclusion. This document serves to provide a comprehensive review of the current understanding of management pertaining to anticoagulation relating to ECMO.

SGLT-2 Inhibitor Use in Heart Failure: A Review for Nurses.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (empagliflozin, canagliflozin, dapagliflozin, and ertugliflozin) are a new class of heart failure medications that have previously been exclusively utilized in the management of type 2 diabetes mellitus (T2DM). The rationale for using SGLT-2 inhibitors in patients with heart failure has stemmed from recent landmark clinical trials in T2DM in which reductions in mortality and hospitalization for heart failure were first observed. On the basis of these robust outcomes, empagliflozin has further been evaluated in heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction and dapagliflozin solely in the management of HFrEF. While cardiovascular outcomes among each agent vary depending on the patient population, updates among both the American and European guidelines have included SGLT-2 inhibitors as pillars of therapy. The exact mechanisms for how SGLT-2 inhibitors are beneficial in heart failure are unknown, but current hypotheses include multiple metabolic and hemodynamic mechanisms. The purpose of this review is to summarize available literature focusing on the use of the SGLT-2 inhibitors as adjunctive therapy in heart failure, as well as evaluate mechanisms for heart failure benefit, adverse effects, and practical considerations for using these agents in the clinical setting.

The Role of sGC Stimulators and Activators in Heart Failure With Reduced Ejection Fraction.

Over the past decade, soluble guanylate cyclase (sGC) activators and stimulators have been developed and studied to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). The sGC enzyme plays an important role in the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) pathway, that has been largely untargeted by current guideline directed medical therapy (GDMT) for HFrEF. Disruption of the NO-sCG-cGMP pathway can be widely observed in patients with HFrEF leading to endothelial dysfunction. The disruption is caused by an oxidized state resulting in low bioavailability of NO and cGMP. The increase in reactive oxygen species can also result in an oxidized, and subsequently heme free, sGC enzyme that NO is unable to activate, furthering the endothelial dysfunction. The novel sGC stimulators enhance the sensitivity of sGC to NO, and independently stimulate sGC, while the sGC activators target the oxidized and heme free sGC to stimulate cGMP production. This review will discuss the pathophysiologic basis for sGC stimulator and activator use in HFrEF, review the pre-clinical and clinical data, and propose a place in the HFrEF armamentarium for this novel pharmacotherapeutic class.

Tolvaptan for Volume Management in Heart Failure.

Volume management in acute decompensated and chronic heart failure (HF) remains a significant challenge. Although progress has been made in the development of mortality-reducing neurohormonal regimens in the reduced ejection fraction population, no clinical trial has yet demonstrated anything more than symptomatic relief or biomarker reduction with pharmacotherapeutic volume-based interventions made in the acutely decompensated individual or those with evolving outpatient congestion. As the number of patients with HF continues to grow, in addition to HF-related hospitalizations, identifying therapies that have the potential to aid in diuresis more safely and efficaciously is paramount to decreasing inpatient length of stay and preventing unnecessary admissions. More recently, a significant amount of research has been dedicated to the use of vasopressin antagonists, specifically tolvaptan, as adjunctive therapy to loop and thiazide diuretics. Although these agents do not seem to have a pervasive role in fluid management in the acute decompensated and chronic HF populations, they are effective tools to have available for specific clinical situations. This review summarizes the literature surrounding the use of tolvaptan for volume management in congestive HF, as well as offering practical guidance for use of this agent.

Lacosamide-Induced Recurrent Ventricular Tachycardia in the Acute Care Setting.

Lacosamide is a new-generation antiepileptic drug (AED) most commonly used adjunctively in the setting of partial-onset seizures refractory to traditional therapy. We describe the first case report, to our knowledge, of a patient who developed recurrent, sustained ventricular tachycardia with multiple administrations of lacosamide in an acute setting. A 70-year-old woman with a history significant for valvular heart disease was admitted to the inpatient cardiology service for worsening heart failure. On hospital day 7, she received a bioprosthetic aortic valve. Prior to surgery and immediately after, the patient's electrocardiogram (ECG) was normal. After developing multiple generalized tonic-clonic seizures refractory to levetiracetam, fosphenytoin, and valproic acid, the decision was made to initiate lacosamide. Two hours following the second lacosamide dose, the patient developed a wide complex QRS that transitioned into sustained ventricular tachycardia requiring electrical cardioversion. Sustained ventricular tachycardia occurred again, just hours after the third dose of lacosamide was given. Following cessation of lacosamide, the patient's QRS interval normalized and has since had no documented episodes of ventricular tachycardia. Clinicians should be aware of the potential for life-threatening rhythmic disturbances in patients initiated on lacosamide and the need for vigilant ECG, electrolyte, and drug-drug monitoring.

PARADIGM-HF Trial: Secondary Analyses Address Unanswered Questions.

Our aim was to summarize published secondary analyses of the PARADIGM-HF trial. In the original trial, published in September 2014, sacubitril/valsartan significantly reduced the primary composite outcome of cardiovascular death or heart failure hospitalization compared to enalapril. This summary provides a resource for clinicians to review subsequent analyses of the landmark trial evaluating the benefit of sacubitril/valsartan in various subgroups and providing information regarding optimal use of this new therapy in the broader heart failure population. A full list of publications of the existing PARDADIGM-HF post hoc analyses was obtained and summarized, grouped by focus (e.g., severity of illness, tolerability). Twenty-six publications and one abstract analyzing the PARADIGM-HF trial were reviewed, summarizing the most important results that compared the benefits of sacubitril/valsartan to enalapril, including pertinent subgroup information from each analysis. Key publications evaluated the treatment effect of sacubitril/valsartan based on heart failure severity (i.e., ejection fraction or heart failure risk scores), impact on alternate outcomes, influence of additional therapies, tolerability in patients with comorbidities (i.e., diabetes), long-term benefits, and cost-effectiveness. In addition, nine ongoing phase III and phase IV clinical trials with sacubitril/valsartan were briefly summarized to address potential future uses in more extensive heart failure settings. The benefit of sacubitril/valsartan over enalapril for the primary endpoint in the PARADIGM-HF trial is maintained throughout numerous secondary analyses. Though the subgroups analyzed are based on participants from a single clinical trial, clinicians can more confidently incorporate this novel therapy into practice with expanded knowledge of these existing analyses as well as ongoing prospective trials.

Evaluation of Systemic Heparin Versus Bivalirudin in Adult Patients Supported by Extracorporeal Membrane Oxygenation.

Systemic anticoagulation is a standard of care in adult patients supported by extracorporeal membrane oxygenation (ECMO) to prevent circuit thrombosis and subsequent thromboembolic events. Unfractionated heparin has long been considered the anticoagulant of choice, but emerging evidence reports successful ECMO runs with direct thrombin inhibitors. This retrospective study sought to determine whether bivalirudin offers distinct clinical benefits as the anticoagulant of choice in ECMO. Primary end points included thrombotic events during the initial 96 hours of anticoagulation, over the course of their entire ECMO run, and at any time during the admission, as well as in-hospital and 30-day mortality. Secondary end points included percent time within therapeutic range for each anticoagulant, neurologic events, vascular complications, and bleeding. Compared with patients receiving heparin, patients receiving bivalirudin show similar rates of thrombotic events across the three time points (17.9% vs. 9.1%; p = 0.47, 21.4% vs. 11.4%; p = 0.41, and 25% vs. 22.7%; p = 1.00, respectively). In-hospital (32.1% vs. 36.4%; p = 0.91) and 30-day mortality (32.1% vs. 36.4%; p = 0.91) were no different. Similarly, no differences were observed in percent time within therapeutic range (83.0% vs. 87.7%, p = 0.34), neurological events (7.1% vs. 11.4%, p = 0.99), vascular complications (57.1% vs. 38.6%, p = 0.20), or major (25.0% vs. 45.5%, p = 0.13) and minor (25.0% vs. 22.7%, p = 1.00) bleeding. These results suggest that bivalirudin is a viable alternative to heparin for anticoagulation in ECMO but may not offer a clinically significant advantage as the anticoagulant of choice.