Comment in 2022

Nature has evolved creative ways to maintain oxygen homeostasis, but what happens when these adaptations are insufficient? Here we discuss biochemical failure points across the oxygen spectrum from ‘too little’ to ‘too much’ oxygen and their potential contributions to cardiovascular disease.

Sleep modulates cardiovascular health, and recent studies have begun to uncover underlying mechanistic links. An integrated translational approach that combines animal models and human trials will enrich scientific discovery, improve therapy, and help to alleviate the global burden of insufficient sleep and cardiovascular disease.

Although cardiac arrhythmias have been observed and described during and after SARS-CoV-2 infection, rigorous studies designed to untangle the complex relationship between this proinflammatory illness and arrhythmogenesis are limited. Despite a pervasive opinion to the contrary, there is presently no definitive data to establish a causal, viral-specific association between COVID-19 and incident arrhythmia.

In the COVID-19 aftermath, academia experiences an unprecedented drought of postdoctoral researchers. The new generation of scientists refuses to face the low odds of starting their own labs in a competitive arena that does not align with their work–life balance needs. We discuss the possible reasons and potential measures needed to sustain talented and passionate early career researchers in academia.

Studies of the genetic architecture of cardiovascular disease once focused on heritable germline factors. Newer work has shed light on the role of somatic mutations in blood cells. These mechanistic and multi-omics studies, along with phenotypic analyses, offer the prospect of new precision cardiovascular medicine paradigms.

The REVIVED trial provides critical evidence on the management of patients with ischemic left ventricular dysfunction, highlighting the importance of optimal medical therapy. At the same time, it is another reminder of the fact that we are far from reaching adequate representation of women in cardiovascular disease trials.

The COVID-19 pandemic has unleashed a tidal wave of psychological distress. Here we discuss the biobehavioral mechanisms through which psychological distress amplifies the adverse effects of SARS-CoV-2 infection on cardiovascular outcomes. We also examine how the stress of caring for patients with COVID-19 increases cardiovascular risk in healthcare workers.

Genomic sequencing in hemophilia is a high-yield test and clinically useful for diagnosis, assessing the risk of developing neutralizing antibodies (‘inhibitors’) against the affected coagulation factor, pregnancy and neonatal management, and family counseling. New genomic technologies can detect several types of DNA change with high sensitivity. Systematic collection of genotype–phenotype data is important to better understand the genetics of hemophilia.

Disease susceptibility and responsiveness to treatment vary among individuals. To understand this diversity, it is crucial to investigate clinical materials and information from large sets of individuals, such as data that can be obtained from biobanks. BioBank Japan is one of the largest biobanks in East Asia and has a complementary role to biobanks from other populations, such as the UK Biobank, given the presence of diverse ethnic variations.

The US FDA recently approved mavacamten, a first-in-class myosin modulator, for obstructive hypertrophic cardiomyopathy. By targeting actin mechanobiology, myosin modulators are emerging as important medicines in cardiology.

Studies over the past five years showing megakaryocytes in tissues beyond the bone marrow have led scientists to question the definition and purpose of these cells beyond platelet production. Here, we look to evolutionary biology to understand the roles of megakaryocytes in platelet function and diversity and mammalian fitness.

Recognition of mechanistic similarities and the interconnection between cardiovascular disease and cancer in recent years offers an opportunity to think more creatively about therapeutic development. Targeting shared pathways, either through drug repurposing or novel compounds, holds the promise of addressing both afflictions at the same time.

Fibrosis is a common sequela of cardiovascular disease that results in structural and functional changes. Targeting the subsets of pathogenic cardiac fibroblasts may be an attractive option for reducing morbidity that is associated with heart disease, but the timing, specificity and extent to which fibroblast-targeting therapies might be used is still debated.

After three decades of work, hypothesis-generating genomic approaches have led to the identification of several intracranial aneurysm risk loci and Mendelian mutations, involving several unexpected genes. These findings opened the door for exciting opportunities, unraveling the genomic architecture of brain aneurysms. The field is now ripe to face the next set of surprises in this long journey.

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.

Improving standards of care and new therapeutics means individuals with cystic fibrosis are living longer, but this brings an increased risk of non-communicable diseases, especially cardiovascular disease (CVD). To improve both longevity and quality of life, it is important to consider CVD risk and prevention in those living with cystic fibrosis.

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.

How do we measure the impact of scientific research? A new study discusses the current publication culture, diverse animal models that are commonly used in cardiovascular studies, the comparison between basic and clinical research paths, and the role of authors and reviewers in bringing these two paths together.