Volume 1 Issue 3, March 2022

The intended purpose of machine learning (ML) in cardiovascular medicine is to help guide clinical diagnoses as well as promote scientific discovery. Whether ML is implemented by most clinical cardiologists and cardiovascular researchers will likely depend on the successful resolution of concerns fueling hesitancy to embrace ML. This commentary discusses caveats related to ML in clinical practice, and offers suggestions for stakeholders on how to bridge knowledge gaps and clinicians’ misgivings to bring this powerful approach to the clinic to improve care of the patients we serve.

The amount of iron in the body and the concentration of iron in blood plasma are closely regulated by an endocrine system centered on the binding of the hormone hepcidin to its receptor and cellular iron exporter ferroportin. The discovery of hepcidin, the mechanisms of its action and its regulation have transformed our understanding of the pathogenesis of iron-related diseases from anemias to hemochromatosis and have led to the development of novel therapeutics for iron disorders.

Statins continue to make a difference and are here to stay. A new study provides further evidence that statins can function beyond inhibition of cholesterol synthesis by increasing the rate of macrophage efferocytosis, via a reduction in the ‘don’t eat me’ signal CD47, thereby decreasing the atherosclerotic plaque burden.

ABCA1 promotes the efflux of cholesterol from cells to HDL and has anti-atherogenic activities. Sun and Li present cryo-EM structures of ABCA1 in the ATP-free and ATP-bound states, which reveal bound cholesterol molecules and suggest a transmembrane cholesterol-transport mechanism.

Mauro Giacca and Ajay M. Shah discuss the most recent advances in the bidirectional relationship between COVID-19 and an array of cardiovascular diseases.

Joseph A. Hill and colleagues discuss basic and translational data focusing on the most common form of heart failure with preserved ejection fraction (HFpEF), cardiometabolic HFpEF, emphasizing the bidirectional cross-talk between metabolic dysregulation triggering immune events—and vice versa—in syndrome pathogenesis.

In this Review, Hwa and colleagues summarize the latest advances in platelet biology and function and appraise the technical and biological challenges in platelet investigations.

Sun and Li propose and validate a model for cholesterol engagement and transport via the ATP-binding cassette transporter ABCA1, via generating and comparing high-resolution cryo-EM structures of three distinct states of the transporter: with and without ATP and a mutant form unable to export cholesterol that is relevant to human pathology

Snellings et al. show that an identical PIK3CA mutation is found in both developmental venous anomalies (DVAs) and associated cerebral cavernous malformations (CCMs). However, an activating MAP3K3 mutation appears only in CCMs, supporting a mechanism where DVAs develop as the result of a PIK3CA mutation.

Jarr and colleagues show that statins augment efferocytosis by inhibiting the nuclear translocation of NF-κB1 p50 and suppressing the expression of the key ‘don’t-eat-me’ molecule CD47, which in part explains the pleiotropic effects of statins and provides a basis for future translational efforts.

Koenig et al. present integrated single-cell and single-nucleus RNA-sequencing data of cardiac samples obtained from 27 healthy donors and 18 individuals with dilated cardiomyopathy. This extensive resource provides insights on cell composition and gene expression changes driven by the disease status, sex or age of the patients.