Reviews & Analysis

The metabolism of lipids accumulated in blood vessel walls and the heart produces sphingolipids, such as ceramides, which are associated with the development of diabetes mellitus, atherosclerosis, hypertension and heart failure. In this Review, the authors discuss ceramides as drivers of cardiovascular disease and therapeutic strategies to lower plasma and cardiac levels of ceramides.

In this Review, Sermesant and colleagues discuss the applications of artificial intelligence (AI) in cardiovascular imaging and explain how pre-existing clinical knowledge can be included in AI methods to increase robustness. They also discuss the limitations of AI approaches in cardiovascular imaging and how they can be overcome.

In this Review, Holmes and colleagues compare and contrast the use of Mendelian randomization to evaluate potential drug targets versus quantitative traits and explain how genetic epidemiological studies can be used to assess the aetiological roles of biomarkers in disease and to prioritize drug targets, including designing their evaluation in clinical trials.

In this Review, Elshazly and colleagues summarize the basic engineering principles of common wearable sensors and discuss their broad applications in cardiovascular disease prevention, diagnosis and management.

In this Review, Nahrendorf and colleagues discuss the electrophysiological properties of leukocytes and how these cells relate to conduction in the heart, aiming to bridge the knowledge gap between electrophysiology and immunology and to explore the roles of leukocytes in cardiac conduction and arrhythmia.

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.

In this Review, Simons and colleagues present the current knowledge of organ-specific signalling pathways involved in the maintenance of endothelial quiescence and the pathologies associated with their disruption. This knowledge will assist the development of innovative preventive strategies and identification of new therapeutic targets.

In this Review, Ren and colleagues summarize the latest advances in understanding the unfolded protein response and endoplasmic reticulum stress in the pathogenesis of cardiovascular disease and discuss potential therapeutic strategies aimed at restoring endoplasmic reticulum proteostasis in cardiovascular diseases.

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.

In this Review, Díez and colleagues summarize the mechanisms of diffuse myocardial fibrosis in heart failure, discuss imaging techniques and circulating biomarkers to characterize the variability of this lesion in patients, and highlight the available and potential future therapeutic strategies for personalizing the prevention and reversal of diffuse myocardial fibrosis.

In this Review, Heusch summarizes the pathophysiology of myocardial stunning and hibernation and highlights potential treatments and clinical implications. A better understanding of these characteristic reperfusion phenomena is important for the potential indication for revascularization and its consequences in patients with chronic coronary syndromes.

In this Review, Friedman and colleagues summarize the use of artificial intelligence-enhanced electrocardiography in the detection of cardiovascular disease in at-risk populations, discuss its implications for clinical decision-making in patients with cardiovascular disease and critically appraise potential limitations and unknowns.

For therapeutic materials to be delivered to the heart, several barriers need to be overcome. In this Review, Ishikawa and colleagues discuss strategies for targeted delivery of therapeutic materials to the heart, including the use of adeno-associated viruses and exosomes, with a focus on agents directed at modifying gene expression.

In this Review, Hollenberg and Singer explore the definition, epidemiology, diagnosis and pathophysiology of septic cardiomyopathy, with an emphasis on how best to interpret this condition in the clinical context in order to optimize interventions and improve outcomes.

This Review summarizes the latest knowledge on cardiac lymphatic development, structure and function, discusses the role of the cardiac lymphatics after myocardial injury during fibrotic repair and regeneration, and highlights the therapeutic potential of targeting the cardiac lymphatics in myocardial infarction.

Heart failure with preserved ejection fraction (HFpEF) affects half of all patients with heart failure worldwide. In this Review, Mishra and Kass and provide a roadmap of the signalling pathways and mechanisms of HFpEF that are being characterized and which might lead to more patient-specific therapies and improved clinical outcomes.

Mouse embryonic organoids that model cardiac development ex vivo could be used as a high-throughput, experimentally tractable system to evaluate crucial cell populations and environmental factors that contribute to normal and abnormal cardiogenesis.

Statin nocebo effects have been demonstrated in numerous randomized, double-blind, placebo-controlled and active-controlled trials. Emerging evidence suggests that brain pathways might mediate statin nocebo hyperalgesia. Evidence-based pain-management approaches can be used to manage nocebo symptoms that occur during statin therapy.