Reviews & Analysis

The idea of myocardial mechanical reflexes was previously considered, but it struggled to gain traction in mainstream thinking. New research shows PIEZO2 ion channels conferring vagal force sensing in atrial and ventricular myocardium to protect the circulation as blood volume changes with gravity and injury.

Deep learning can identify cardiac abnormalities from echocardiogram videos, but previous work has predominantly used 2D video clips from a single cross-section of the heart. Research now shows that more complex approaches that integrate information from several echocardiographic views can improve deep learning prediction of cardiac abnormalities.

Baudry et al. review the main components and operational considerations for running decentralized clinical trials, outline their specific advantages for the cardiovascular field, and propose strategies to mitigate their downsides and ensure their quality.

Yeow et al. review the pathogenesis of rheumatic heart disease, discuss the role of valve biology in the progression of the disease, highlight ongoing research to address the critical healthcare burden and describe recent advances into the underlying pathogenic mechanisms.

Baudry et al. review regional participation in heart failure clinical trials, summarize region-specific and regulatory elements that hinder the participation of underrepresented regions, and propose strategies to overcome these obstacles.

We performed single-nucleus and spatial transcriptomic analyses of systemic right ventricles from pediatric donors with hypoplastic left heart syndrome after surgical palliation. Our analyses demonstrate widespread senescence in the failing heart, spatially organized into microvascular niches, and show that these pathological states are partially reversible with mechanical unloading.

Idiopathic pulmonary arterial hypertension is a rare, progressive and life-limiting disease that is difficult to diagnose because of its nonspecific symptoms and reliance on invasive right-heart catheterization for diagnosis. Diagnostic delays contribute to a highly heterogeneous patient population. Current blood biomarkers reflect mainly secondary cardiac strain rather than pulmonary vascular pathology, but a new paper highlights the NOTCH3 extracellular domain as a pulmonary vasculature- and idiopathic-specific blood biomarker to support diagnosis and prognosis.

Aberrant immunometabolic signaling promotes cardiac remodeling in type 2 diabetes. Targeting this axis by enhancing the migratory capacity of regulatory T cells improves diabetic cardiomyopathy.

Aortic stenosis is a common cause of valve disease and has a genetic basis. Two complementary papers perform genome-wide association studies: first, of aortic stenosis cases, and second, on aortic valve structure and function. These findings provide a strong foundation for the future development of medical therapy for aortic stenosis.

A smart magnetoelastic stent has now been developed to prevent in-stent restenosis after implantation.

Systemic glucocorticoids actively suppress the intrinsic regenerative capacity of the heart by enforcing a molecular brake on growth factor signaling. A study now shows that transient antagonism of glucocorticoid receptor signaling can lift this restriction and synergize with regenerative cues to restore cardiac repair in vivo.

Diverse mutations in RPL3L, the muscle-specific paralog of the ribosomal protein RPL3, have been associated with severe infantile dilated cardiomyopathy and often fatal heart failure. We show that disease is primarily driven by hotspot RPL3L variants that simultaneously block ribosome biogenesis and induce unproductive splicing of the RPL3 precursor mRNA, thereby preventing any compensatory effects of the ubiquitously expressed RPL3.

Defects in elastin trigger hyperproliferation of smooth muscle cells, which leads to arterial and congenital heart diseases. Research now shows that elastin deficiency induces SPHK1 and S1P signaling by EGR1 in SMCs, and inhibitors of SPHK1 or S1PR1 attenuate smooth muscle cell proliferation and mitigate aortic disease.

Correlating the mitochondrial membrane potential with the redox status of endogenous mitochondrial cytochromes in vitro enabled the real-time determination of the mitochondrial membrane potential in an isolated perfused mouse heart. This model was used to provide insights into cardiac ischemia–reperfusion injury.

Most drugs in phase 2 trials fail to reach regulatory approval. By leveraging machine learning to identify connections between different types of data, including genes, diseases, medications, existing drugs and images, a new approach is shown to increase the level of evidence in identifying drug targets for cardiovascular disease.

The transcription factor TBX5 regulates early cardiac progenitor cells and genes that encode essential patterning cues for the correct formation of the interventricular septum and separation of cardiac chambers in mice. Disruption of a compartment boundary at the developing interventricular septum reveals potential mechanisms that might underlie some congenital heart defects.

Long COVID is a major global health challenge but the underlying mechanisms are unclear, hampering the development of effective therapies. Evidence points to a causal link between thromboembolic processes and symptom persistence, suggesting a role for vascular and coagulation abnormalities in the pathogenesis of this complex syndrome.

Patsy et al. review the relationship between the heart and the nervous system during development and the functional consequences of cardiac innervation. They describe the generation of cardiomyocytes and autonomic neurons and propose a roadmap toward the development of cardiac innervation models.

We developed an adeno-associated virus-based, conditional and reversible gene therapy. Using this approach to transiently induce YAP activation in cardiomyocytes either before or after ischemic injury in mice, we could improve cardiac function.

Genome-wide association studies (GWAS) in coronary artery disease have revealed gene variants highly expressed in vascular smooth muscles cells (SMCs). Research now suggests that loss of one, Prdm16, drives a switch toward a synthetic SMC phenotype, with robust, potentially protective extracellular matrix production and fibrous cap formation.