News & Views

Two studies published in Nature report the structure of apolipoprotein B100 on LDL using high-resolution, artificial intelligence-assisted cryo-electron microscopy and uncover its precise molecular interfaces with the LDL receptor. Dimers of LDL particles connected by a pair of receptors are also visualized for the first time. These studies provide key structural insights into the molecular defects linked to familial hypercholesterolaemia and open exciting avenues for translational research and drug development.

Macrophage–fibroblast interactions have a central role in cardiac fibrosis. In response to left ventricular pressure overload, CCR2⁺ cardiac macrophages acquire a fibrogenic phenotype, secreting IL-1β and promoting the activation of a FAP⁺ POSTN⁺ fibroblast subpopulation through the transcription factor MEOX1. Macrophage-derived fibroblast-activating cytokines (such as IL-1β), growth factors and matricellular proteins contribute to the pathogenesis of heart failure.

Consumption of a high-fat diet leads to the progressive growth of atherosclerotic lesions. Two new studies document that, despite similar overall exposure to high-fat diet over a lifetime, an intermittent consumption of high-fat diet early in life accelerates atherosclerosis compared with continuous consumption of a high-fat diet. The mechanisms for accelerated atherosclerosis include reprogramming of macrophages and neutrophils.

In contrast to the ABYSS investigators’ interpretation of the primary results of their trial, we believe that β-blockers can be safely discontinued in the majority of patients after an uncomplicated myocardial infarction. However, in individuals developing symptoms of angina or heart failure, β-blocker treatment remains one of several guideline-recommended therapies.

A study using advanced single-cell technologies has broadened our understanding of the diversity and complexity of brain endothelial cells by uncovering new endothelial subtypes and transcriptional patterns. These findings offer insights into potential therapeutic targets and emphasize the need for further research on vascular lineages and neurovascular interactions.

Understanding how adverse professional life experiences affect the mental well-being of cardiologists is important. An unmet and equally important need is to design and implement strategies to prevent emotional harassment and discrimination at health-care workplaces and to effectively support cardiologists who have been exposed to adverse professional life experiences. These strategies are especially needed for female, younger or divorced cardiologists.

The STRONG-HF and COACH trials have shown a reduction in morbidity and mortality in patients with acute decompensated heart failure, for whom therapeutical options are currently limited, using two different approaches that have in common the aim of more effective treatment optimization through a better transition phase from in-hospital to outpatient care.

Health-care delivery is evolving, with an increased availability of consumer and medical technology-enabled diagnostic devices powered by artificial intelligence. Physicians need to evolve by deprioritizing old skills in favour of new skills in statistics and medical decision-making psychology. Technology moves fast; physicians will need to pivot and adapt quickly.

Cardiopulmonary resuscitation (CPR) provided by a bystander has saved the lives of many patients with out-of-hospital cardiac arrest. Several factors have been hypothesized to contribute to the low rates of bystander CPR, including the race and/or ethnicity of the recipient and the location of the out-of-hospital cardiac arrest.

Cardiovascular disease is both a risk factor and potential outcome of the direct, indirect and long-term effects of COVID-19. A recent analysis in >150,000 survivors of COVID-19 demonstrates an increased 1-year risk of numerous cardiovascular diseases. Preventing and managing this new disease burden presents challenges to health systems and requires a learning health system approach.

A new, very large genome-wide association study has uncovered many novel genetic factors associated with circulating lipid levels. The success of this study came partly from analysing many samples, but mostly from including individuals of non-European ancestry. So, why is studying genetic diversity important and how can it help to fight cardiovascular disease?

In a pooled analysis of 144 high-quality randomized trials involving patients with coronary artery disease, application of the most stringent criteria for surrogacy demonstrated that a reduction in the rates of non-fatal myocardial infarction by any intervention did not necessarily predict a reduction in all-cause or cardiovascular mortality during follow-up.

Care pathways for ST-segment elevation myocardial infarction (STEMI) were interrupted during the coronavirus disease 2019 (COVID-19) pandemic. A new cardiac MRI study has revealed that increased total ischaemic time for patients with STEMI during major public health restrictions was associated with increased infarct size and other markers of myocardial damage.

The field of cardiac cell therapy is under siege. Legacies of excessive hype, scientific misconduct and dead ends have fuelled the prevailing scepticism. However, promising clinical data, along with more trenchant mechanistic understanding, together provide glimmers of hope for the future of cell therapy for the heart.

Nanotherapies are emerging rapidly as options to treat cardiovascular disease. However, insufficient and heterogeneous delivery remain critical issues. Novel strategies to boost targeted delivery of systemically administered nanoparticles by optimizing the particle physical properties or using immune cells as carriers promise to increase nanotherapeutic effectiveness in cardiovascular and other inflammatory diseases.

Mounting evidence from the SPRINT trial and the Blood Pressure Lowering Treatment Trialists points towards the use of absolute cardiovascular risk assessment to guide blood-pressure management. But who will fall between the cracks? We need to be pragmatic in keeping blood-pressure targets, if only to serve the >1 billion people at risk of cardiovascular disease living in low-resource settings.

Surgical mitral valve repair produces exceptional long-term survival, durable relief from mitral regurgitation, and physiological valve performance. Percutaneous mitral valve repair might prohibit subsequent surgical reconstruction. This finding has important implications, including for patient consent and clinical trial design. The objectives of mitral valve intervention must focus on life expectancy and long-term valve function.

Sequencing studies demonstrate a strong clinical association between clonal haematopoiesis driven by acquired mutations and atherosclerotic disease. Previous research supports the idea that this association reflects a direct contribution of some clonal haematopoiesis-related mutations to atherosclerosis. Now, mathematical modelling suggests that atherosclerosis could instead accelerate clonal haematopoiesis.

Although an unplanned, interim analysis from an ongoing randomized trial in Sweden has suggested no significant difference in mortality between patients with peripheral artery disease receiving paclitaxel-coated devices and those receiving uncoated devices for lower-extremity revascularization, the analysis did not resolve the question of whether paclitaxel-coated devices are safe for these patients.

Valve replacement is currently the only treatment for calcific aortic valve disease. Studies of an uncommon, genetic form of aortic valve disease have yielded in vitro and mouse models of the disease and a transcriptomic disease signature. Machine learning-driven screens for compounds that normalize this signature promise to enable medical management of aortic valve disease.