Comment

Apheresis, introduced 50 years ago, remains a crucial therapy for homozygous familial hypercholesterolemia, a rare gene disorder that causes extreme LDL-cholesterol levels and early cardiovascular death. This Comment also honors the late professor Thompson, a pioneer of apheresis, whose work helped to shape the field.

The 2025 Nobel Prize in Physiology or Medicine honored a scientific breakthrough with hidden cardiovascular potential: regulatory T cells and peripheral immune tolerance. These mechanisms provide a paradigm shift for understanding and treating cardiovascular disease, dampening inflammation without compromising immunity, and offering safer and more effective therapies.

There is great interest in modeling human HFpEF in animals to identify underlying mechanisms and ultimately improve sorely needed therapies. Our current models are a step forward but still fall short in several crucial ways, particularly by not capturing the severity of heart failure features common in patients.

Heart failure and cancer share risk factors and biological pathways, yet their interplay remains underexplored. This Comment calls for coordinated research, precision medicine approaches and policy changes to advance the emerging field of cardio-oncology.

Low-dose colchicine is the only anti-inflammatory drug approved for secondary prevention of coronary disease. The CLEAR-SYNGERY trial of colchicine in acute myocardial infarction challenges the results of previous colchicine trials; however, clinicians should be aware of how its design and the COVID-19 pandemic affected the trial outcome.

The PET radiotracer ¹⁸F-flurpiridaz has undergone rigorous clinical testing and gained FDA approval for the evaluation of coronary artery disease. Its unique properties suggest ¹⁸F-flurpiridaz has the potential to transform the field of nuclear myocardial perfusion imaging and blood flow quantification, with far-reaching effects on cardiovascular care.

The discovery of the genes causing cerebral cavernous malformation (CCM) initially heralded a fruitful search for etiopathogenic molecular pathways in this rare cerebrovascular disease. Recent studies have identified the relevance of CCM proteins for much more common vascular biology and pathologies.

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.