Calcium (Ca²⁺) signalling is essential for cardiomyocyte function, regulating excitation-contraction coupling and excitation-transcription coupling, and contributing to mitochondrial energy production (excitation-bioener...Calcium (Ca²⁺) signalling is essential for cardiomyocyte function, regulating excitation-contraction coupling and excitation-transcription coupling, and contributing to mitochondrial energy production (excitation-bioenergetics coupling). In this Review, we explore the role of Ca²⁺ microdomains, which compartmentalize Ca²⁺ signalling to ensure efficient cardiac function. We first describe the organization of these microdomains, followed by their functional importance, pathological alterations in heart failure and potential therapeutic strategies targeting key Ca²⁺-signalling mechanisms. The dyad, a crucial excitation-contraction coupling microdomain, brings L-type Ca²⁺ channels and ryanodine receptor Ca²⁺-release channels (RYR2) into close proximity, facilitating Ca²⁺-induced Ca²⁺ release for cardiomyocyte contraction. In heart failure, dyadic remodelling and altered Ca²⁺ handling contribute to cardiac contractile dysfunction and arrhythmogenesis. Emerging research shows that dyads are dynamic, rapidly adapting to modulators such as β-adrenergic signalling, offering new therapeutic targets. Under stress conditions, dyadic proteins can translocate to the nucleus to regulate gene expression. In addition to excitation-contraction coupling, which operates on a beat-to-beat basis, Ca²⁺ has additional roles in cardiomyocytes. Nuclear Ca²⁺ regulates the expression of genes related to hypertrophy, including those encoding Ca²⁺ channels and transporters. Disruptions in these microdomains drive pathological remodelling in heart failure and arrhythmias. Understanding Ca²⁺ microdomains is crucial for developing targeted interventions to restore cardiac function while minimizing pro-arrhythmic risks.
Conventional, rigid simulators and therapeutic devices for cardiovascular disease have several fundamental limitations, such as poor biomimetic fidelity, substantial surgical invasiveness and mismatch at the tissue-devic...Conventional, rigid simulators and therapeutic devices for cardiovascular disease have several fundamental limitations, such as poor biomimetic fidelity, substantial surgical invasiveness and mismatch at the tissue-device interface. Soft robotic devices, with tissue-like materials, structures and functions, are emerging as promising alternatives. In this Review, by matching clinical demands to technological breakthroughs, we identify three emerging complementary frontiers in which soft robotic devices are redefining cardiovascular medicine - soft robotic simulators, such as in vitro ventricular simulators and in vivo assistive simulators; soft robotic interventional instruments, such as percutaneous instruments, endovascular continuum instruments and untethered mini-scale robots; and soft robotic implants for vascular disease, arrhythmia and heart failure. We describe the unique advantages of soft robotic devices as well as their applicable scope and technical implementation. Finally, we highlight promising technological opportunities for next-generation soft cardiac devices, evaluate the clinical maturity of existing devices and propose a translational roadmap for the coming decade. With this Review, we aim to foster further integration of soft robotics into cardiovascular medicine by identifying device solutions with translational potential to address unmet clinical needs.
Over the past two decades, stents have revolutionized the treatment of cardiovascular diseases, particularly coronary artery and valvular heart disease. In this Review, we evaluate the clinical challenges associated with...Over the past two decades, stents have revolutionized the treatment of cardiovascular diseases, particularly coronary artery and valvular heart disease. In this Review, we evaluate the clinical challenges associated with these diseases, as well as the manufacturing strategies for both coronary and heart valve stents, with a focus on the emerging role of 3D printing. Specifically, we assess the advantages and limitations of clinically available metallic and polymeric stents for coronary artery disease and provide an overview of the metallic and biodegradable polymeric stents developed to treat valvular heart disease. Furthermore, we explore the capabilities of key 3D-printing methods for stent fabrication, highlighting their strengths and drawbacks, and discuss the regulatory considerations that govern the clinical translation of 3D printing-based coronary and valvular stents. Taken together, 3D-printing technologies offer new opportunities to customize geometry, control stent degradation and improve stent implantation approaches for patients with complex anatomies. By merging innovations in material science, manufacturing strategies and bioengineering, 3D-printing technology has a major role in the next generation of personalized and multifunctional cardiovascular stents.
Myocarditis is a clinically and aetiologically heterogeneous disease that is associated with substantial morbidity and mortality, with approximately a million new cases and 17,000 deaths annually worldwide. However, the...Myocarditis is a clinically and aetiologically heterogeneous disease that is associated with substantial morbidity and mortality, with approximately a million new cases and 17,000 deaths annually worldwide. However, the incidence of myocarditis varies widely by geographical region, sex and age. The aetiology of myocarditis is multifactorial and shaped by regional, demographic and socioeconomic contexts. In high-income countries, parvovirus B19 and human herpesvirus 6 are the predominant cardiotropic viruses that induce lymphocytic myocarditis, particularly in children. By contrast, in low-to-middle-income countries, dengue virus, human immunodeficiency virus, Plasmodium spp. (malaria) and Trypanosoma cruzi (Chagas disease) are the most common causative pathogens. Systemic autoimmune conditions and genetic predisposition are also implicated in the development of myocarditis, and increasingly recognized iatrogenic triggers of myocarditis include immune checkpoint inhibitors and gene therapies. This Review synthesizes epidemiological insights across diverse age groups and geographical regions, with a particular emphasis on the undiagnosed disease burden in low-resource settings. Variability in diagnostic criteria and the scarcity of heart-biopsy-confirmed data pose challenges to accurate estimates of global prevalence. Priorities for future research include multicentric registries, multi-omics-based risk stratification, and integration of novel biomarkers and advanced imaging techniques to refine myocarditis surveillance and treatment, and improve the accuracy of disease burden estimates.
Drug-coated balloons (DCBs) are devices used for the treatment of both coronary artery disease (CAD) and peripheral artery disease (PAD). One of the hypothesized advantages of DCB angioplasty over stent implantation is t...Drug-coated balloons (DCBs) are devices used for the treatment of both coronary artery disease (CAD) and peripheral artery disease (PAD). One of the hypothesized advantages of DCB angioplasty over stent implantation is that DCB angioplasty does not result in the presence of a permanent metallic scaffold in the vessel wall. However, DCB angioplasty also has some important limitations, such as a potentially lower efficacy compared with other modalities; therefore, the role of DCBs in the treatment of CAD and PAD is not fully defined. Over the past 20 years, many clinical trials have been performed to investigate the use of these devices for a variety of indications. In this Review, we describe the device design and mechanism of action of DCBs and discuss important procedural considerations for successful DCB use. We summarize the scientific and clinical evidence for DCB angioplasty in CAD and PAD. In addition, we highlight the recommendations for DCB use in clinical practice guidelines and provide perspectives on the potential future role that DCB angioplasty might have in the treatment of CAD and PAD.