Marin Nishimura

Reversal agents for direct oral anticoagulants: A focused review

For several decades the vitamin K antagonist oral anticoagulants were the only outpatient therapy that existed to reduce the risk of stroke and thromboembolism. When the new direct oral anticoagulants were approved for use and addressed many of the issues associated with oral vitamin K antagonists, a new concern arose-the lack of rapid ability to reverse these agents. Physicians and patients were concerned that in cases of life-threatening bleeding or need for emergent surgery, an antidote to reverse the anticoagulation effect of these agents did not exist. Contemporary research has aimed to produce reversal agents that can be administered to safely neutralize the anticoagulant effect. In this focused review we describe the clinical development as well as mechanisms of action of three agents (idarucizumab, andexanet alpha, and ciraparantag). We review the pharmacokinetics, animal and human study data of these reversal agents and outline the evidence supporting their use. Although questions of safety and appropriate use remain, these reversal agents offer a significant step forward in the widespread use of direct oral anticoagulants and overall management of the anticoagulant effect.

Non–Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and End-Stage Renal Disease

Over the past decade, there have been tremendous advancements in anticoagulation therapies for stroke prevention in patients with atrial fibrillation (AF). Although the non-vitamin K antagonist oral anticoagulants (NOACs) demonstrated favorable clinical outcomes compared with warfarin overall, the decision to anticoagulate and the choice of appropriate agent in patients with AF and concomitant chronic kidney disease (CKD) or end-stage renal disease (ESRD) are a particularly complex issue. CKD and ESRD increase both the risk of stroke and bleeding, and since all of the NOACs undergo various levels of renal clearance, renal dysfunction inevitably affects the pharmacokinetics of the drug in each patient. Furthermore, the randomized controlled clinical trials of each NOAC versus warfarin often did not include patients with advanced CKD or ESRD. In this focused review, we describe the available evidence supporting the use of NOACs for prevention of stroke in patients with AF with concomitant advanced CKD or ESRD. Although questions of safety and appropriate use of these new agents in CKD and ESRD remain, NOACs offer a significant step forward in the anticoagulation management of at-risk patients with AF.

Percutaneous left atrial appendage occlusion in atrial fibrillation patients with a contraindication to oral anticoagulation: a focused review

Stroke is the most feared complication of atrial fibrillation (AF). Although oral anticoagulation with non-vitamin K antagonist and non-vitamin K antagonist oral anticoagulants (NOACs) have been established to significantly reduce risk of stroke, real-world use of these agents are often suboptimal due to concerns for adverse events including bleeding from both patients and clinicians. Particularly in patients with previous serious bleeding, oral anticoagulation may be contraindicated. Left atrial appendage occlusion (LAAO), mechanically targeting the source of most of the thrombi in AF, holds an immense potential as an alternative to OAC in management of stroke prophylaxis. In this focused review, we describe the available evidence of various LAAO devices, detailing data regarding their use in patients with a contraindication for oral anticoagulation. Although some questions of safety and appropriate use of these new devices in patients who cannot tolerate anticoagulation remain, LAAO devices offer a significant step forward in the management of patients with AF, including those patients who may not be able to be prescribed OAC at all. Future studies involving patients fully contraindicated to OAC are warranted in the era of LAAO devices for stroke risk reduction.

The Confounding Effects of Non-cardiac Pathologies on the Interpretation of Cardiac Biomarkers

Purpose of ReviewCardiac biomarkers play important roles in routine evaluation of cardiac patients. But while these biomarkers can be extremely valuable, none of them should ever be used by themselves—without adding the clinical context. This paper explores the non-cardiac pathologies that can be seen with the cardiac biomarkers most commonly used.Recent FindingsHigh-sensitivity troponin assay gained FDA approval for use in the USA, and studies demonstrated its diagnostic utility can be extended to patients with renal impairment. Gender-specific cut points may be utilized for high-sensitivity troponin assays. In the realm of the natriuretic peptides, studies demonstrated states of natriuretic peptide deficiency in obesity and in subjects of African-American race. Regardless, BNP and NT-proBNP both retained prognostic utilities across a variety of comorbid conditions. We are rapidly gaining clinical evidence with use of soluble ST2 and procalcitonin levels in management of cardiac disease states.SummaryIn order to get the most utility from their measurement, one must be aware of non-cardiac pathologies that may affect the levels of biomarkers as although many of these are actually true values, they may not represent the disease we are trying to delineate.A few take-home points are as follows:1.A biomarker value should never be used without clinical context2.Serial sampling of biomarkers is often helpful3.Panels of biomarkers may be valuable

Current and Future Use of Insertable Cardiac Monitors

Insertable cardiac monitors (ICMs) are small, subcutaneously implanted devices offering continuous ambulatory electrocardiogram monitoring with a lifespan up to 3 years. ICMs have been studied and proven useful in selected cases of unexplained syncope and palpitations, as well as in atrial fibrillation (AF) management. The use of ICMs has greatly improved our ability to detect subclinical AF after cryptogenic stroke, and application of this technology is growing. Despite this, current stroke and cardiology society guidelines are lacking in recommendations for monitoring of subclinical AF following cryptogenic stroke, including the optimal timing from stroke event, duration, and method of electrocardiogram monitoring. This focused review outlines the current society guidelines, summarizes the latest evidence, and describes current and future use of ICMs with an emphasis on detection of subclinical AF in patients with cryptogenic stroke.

Reply: A Cautionary Tone Before Expanded Adoption of the Proposed CHA2DS2-VASc R Score

We applaud Kabra et al. (1) for their highly relevant study demonstrating additional stroke risk of AfricanAmerican ethnicity in patients with atrial fibrillation (AF) (1). Calculation of the CHA2DS2-VASc (congestive heart failure, hypertension, age

THE PREVALENCE AND CLINICAL SIGNIFICANCE OF COMPACTED MYOCARDIUM IN DILATED CARDIOMYOPATHY: A CONTRAST ECHOCARDIOGRAPHY STUDY

75 years, diabetes, previous stroke, vascular disease, age 65 to 74 years, and female sex) score is an integral aspect of AF management, and the findings of their study suggest that race adds an additional element to risk stratification in patients with AF. In the United States, it is well known that the prevalence of oral anticoagulation prescription across the spectrum of CHA2DS2-VASc scores falls below guideline-based expectations (2). Although the findings of Kabra et al. (1) are extremely important, we would like to highlight a cautionary tone on the full extrapolation of the results. Due to the inclusion criteria (patients

Gonadotropin-Releasing Hormone Induces miR-132 and miR-212 to Regulate Cellular Morphology and Migration in Immortalized LβT2 Pituitary Gonadotrope Cells

66 years of age), only 1% of the study population had a CHA2DS2-VASc score of 1. This detail is important for 2 main reasons. First, the fact that only 1% of the study population had a CHA2DS2VASc score of 1 is illustrative of the influence of age in the accumulation of points using the CHA2DS2-VASc score. The proportion of patients with a CHA2DS2VASc score of 1 in clinical practice is much higher, ranging from 8.6% to 14.9% (2,3), which likely reflects the preponderance of a single additional point risk factor in younger patients (<65 years of age). Second, it is exactly this critical subpopulation with CHA2DS2VASc scores of 1 that would be most affected by the adoption of the CHA2DS2-VASc R system, as 2 points is the current guideline-based threshold to recommend oral anticoagulation based on the CHA2DS2-VASc score (4). In these patients with CHA2DS2-VASc scores of 1, African-American race would give a CHA2DS2-VASc R score of 2 and thus appear to warrant a strong recommendation for oral anticoagulation therapy. However, it is difficult to extrapolate this investigation’s findings to clinical practice when patients with CHA2DS2-VASc scores of 1 represented only 1% of the studied cohort due to the exclusion of patients #65 years of age. Although we congratulate the authors (1) for their important work, we believe that additional studies need to be performed to investigate the association of race with stroke, particularly in patients #65 years of age, before changing guidelinebased practice.

Abstract 14066: Methamphetamine Associated Heart Failure, a New Epidemic

Background: Patients with dilated cardiomyopathy(DCM) often demonstrate prominent trabeculae in the presence of a diminished thickness of compacted myocardium; a condition that can be well delineated by contrast echocardiography(CON). The goal of this study was to use CON to define the prevalence