Comment

Although anti-inflammatory drugs have shown promising results in preclinical cardiovascular research, they have yielded little benefit in clinical trials. Before we can expect positive outcomes, we need to find ways of stratifying patients based on their infectious, inflammatory and autoimmune profile, and identify the right time of treatment.

In the USA, scientific merit is the main criterion determining funding for biomedical research, but not for the institutional space or support needed to perform it. Realigning the incentives of academic institutions with those of funding sources could produce better science.

Continuous cardiac rhythm monitoring via cardiac implantable electronic devices finds an increased number of patients with asymptomatic atrial fibrillation. Yet, not all patients with device-detected atrial high-rate episodes are alike. Fine-tuning risk assessment may help identify those who can benefit most from anticoagulation.

Several experimental systems have been used over the past five decades to address important questions in cardiac development and congenital heart disease. Here we discuss the strengths and limitations of available models, and how the use of different models synergistically is needed for a deeper understanding of these complex diseases.

The US Food and Drug Administration (FDA) has approved sotagliflozin with a broad heart-failure indication, even in the absence of trial data in patients without diabetes. No one knows what the benefits or risks of inhibiting SGLT1 in the heart might be.

Sotatercept is the first successful therapy to make it through phase 3 to regulatory submission in pulmonary arterial hypertension that is not proposed to work via vasodilatory mechanisms. The phase 3 STELLAR study of sotatercept treatment challenges established thinking on pulmonary vascular remodeling and offers patients hope for a step change in outcomes.

Over recent decades, shifts toward translational or applied research in many countries have come at the expense of fundamental discovery research. Here we discuss the historical importance of basic science in the cardiovascular field, the risks in its decline and the ongoing need for a strong foundation in fundamental discovery research.

The rapid development of single-cell transcriptomics, epigenomics, proteomics and metabolomics has resulted in a wave of new biological discoveries. Here we explore what this has meant for the cardiovascular field and what the future might hold for developing treatments for patients.

Pregnancy is associated with a substantial risk of short-term and long-term cardiovascular diseases. Here we discuss physiological and social factors that affect the risk of pregnancy-related cardiovascular diseases and opportunities to improve outcomes.

Iron is essential to the production of myocardial energy and proteins critical for cardiovascular function. Nearly 50% of patients with heart failure with reduced ejection fraction (HFrEF) meet current criteria for iron deficiency, and there has been considerable interest in intravenous repletion of iron stores as a therapeutic strategy to improve HFrEF outcomes. However, the data on intravenous iron therapy in HFrEF have been mixed.

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.