Diversity in modern heart failure trials: Where are we, and where are we going.

Over the last three decades, increased attention has been given to the representation of historically underrepresented groups within the landscape of pivotal clinical trials. However, recent events (i.e., coronavirus pandemic) have laid bare the potential continuation of historic inequities in available clinical trials and studies aimed at the care of broad patient populations. Anecdotally, cardiovascular disease (CVD) has not been immune to these disparities. Within this review, we examine and discuss recent landmark CVD trials, with a specific focus on the representation of Blacks within several critically foundational heart failure clinical trials tied to contemporary treatment strategies and drug approvals. We also discuss solutions for inequities within the landscape of cardiovascular trials. Building a more diverse clinical trial workforce coupled with intentional efforts to increase clinical trial diversity will advance equity in cardiovascular care.

Usefulness of Integrating Heart Failure Risk Factors Into Impairment of Global Longitudinal Strain to Predict Anthracycline-Related Cardiac Dysfunction.

The prediction of cancer therapeutics-related cardiac dysfunction (CTRCD) is an essential aspect of care for individuals who receive potentially cardiotoxic oncologic treatments. Certain clinical risk factors have been described for incident CTRCD, and measurement of left ventricular (LV) longitudinal strain by speckle tracking 2-dimensional echocardiography (2DE) is the best-validated myocardial mechanical imaging assessment to detect subtle changes in LV function during cancer treatment. However, the direct integration of clinical and imaging risk factors to predict CTRCD has not yet been extensively examined. This was a retrospective study of 183 women with breast cancer aged 50.9 ± 10.8 years who received treatment with anthracyclines (doxorubicin dose of 422 ± 69 mg/m2, with 41.2% of subjects also receiving trastuzumab) and underwent 2DE at clinically determined intervals. CTRCD was diagnosed when LV ejection fraction dropped ≥10% to a subnormal (<53%) value by 2DE. Left ventricular global longitudinal strain (LV-GLS) was assessed offline. The risk prediction tool based only on clinical factors previously described by Ezaz et al was applied to our cohort and accurately stratified these subjects into low-, intermediate-, and high-risk groups, with incident CTRCD in 7.4%, 26.9%, and 54.6%, respectively (chi-square = 20.7, p <0.0001). We developed novel multivariate models to predict CTRCD using (1) demographic variables only (c = 0.8674), (2) echocardiographic (peak LV-GLS) variables only (c = 0.8440), or (3) a combination of demographic and echocardiographic variables, with the combined model exhibiting superior receiver-operating characteristics (c = 0.9629). In conclusion, estimation of CTRCD risk should integrate all available data, including both clinical variables and an imaging assessment.

The current approach of atrial fibrillation management.

Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice. Aging populations coupled with improved outcomes for many chronic medical conditions has led to increases in AF diagnoses. AF is also known to be associated with an increased risk of adverse events such as transient ischemic attack, ischemic stroke, systemic embolism, and death. This association is enhanced in select populations with preexisting comorbid conditions such as chronic heart failure. The aim of this review is to highlight the advances in the field of cardiology in the management of AF in both acute and long-term settings. We will also review the evolution of anticoagulation management over the past few years and landmark trials in the development of novel oral anticoagulants (NOACs), reversal agents for new NOACs, nonpharmacological options to anticoagulation therapy, and the role of implantable loop recorder in AF management.

Clinical utility of implantable loop recorders.

Implantable loop recorders provide the highest sensitivity and accuracy of diagnosing cardiac arrhythmia that results in cardiac syncope. When bradyarrhythmia or tachyarrhythmia, including atrial fibrillation, is detected, appropriate secondary prevention therapy will be implemented, which will impact the long-term clinical outcome. An implantable loop recorder enables the clinician to record for a longer period of time, which increases the likelihood of detecting cardiac arrhythmia. Currently, this technology is being evaluated to diagnose a cardiac etiology of ischemic stroke and to optimize atrial fibrillation management that will predict the success of rhythm control and prevent thromboembolic events. This article reviews implantable loop recorder technology, and discusses the current indications, the outcomes of clinical studies and ongoing current studies, and future technological improvements.

Experimental design and multivariate analysis for optimizing poly(D,L-lactide-co-glycolide) (PLGA) nanoparticle synthesis using molecular micelles.

The utility of polymeric nanoparticles as drug delivery systems depends on effective control of synthetic parameters with a significant impact on their physico-chemical characteristics. In this study, a chemometric central composite experimental design (CCD) was used to optimize the synthesis of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles by emulsification solvent evaporation using anionic molecular micelles, such as poly(sodium N-undecylenic sulfate) (poly-SUS), poly(sodium N-undecanoyl-glycinate) (poly-SUG) and poly(sodium N-undecanoyl-L-leucyl-valinate) (poly-L-SULV) as well as conventional emulsifiers, such as anionic sodium dodecyl sulfate (SDS) and non-ionic poly(vinyl alcohol) (PVA). The individual and combined effects of PLGA concentration, emulsifier concentration, homogenization speed, and sonication time (design variables) on particle size and polydispersity index (responses) were investigated using multivariate analysis. The most significant design variables influencing the nanoparticle size and size distribution were PLGA concentration and emulsifier concentration (p < 0.05) in comparison to the other design variables. The quadratic model demonstrated the highest predictive ability when the molecular micelles were used as emulsifiers. The PLGA nanoparticles optimally synthesized according to the CCD were further purified by dialysis and then freeze-dried. Dried nanoparticles synthesized with molecular micelles and PVA were readily re-suspended in water, as compared with SDS for which nanoparticle aggregation occurred. The size of PLGA nanoparticles synthesized using molecular micelles increased after freeze-drying, but remained smaller than 100 nm when poly-L-SULV was used as emulsifier. The PDI values indicated monodisperse nanoparticle suspensions after purification and freeze-drying for all investigated molecular micelles (PDI < 0.100). The nanoparticle suspensions synthesized using molecular micelles were the most stable after dialysis and freeze-drying, having low negative zeta potential values ranging from -54 +/- 1.6 mV for poly-L-SULV to -63.2 +/- 0.4 mV for poly-SUS. Transmission electron microscopy (TEM) micrographs showed spherical shape and smooth surface for the PLGA nanoparticles synthesized using molecular micelles.