Coronary artery obstruction is a rare but devastating complication of transcatheter aortic valve replacement. Current techniques (transcatheter leaflet modification or snorkel stenting) cannot prevent obstruction in all cases.

Catheter ablation of scar-dependent ventricular tachycardia (VT) is frequently hampered by hemodynamic instability, long procedure duration, and high recurrence rates. Magnetic resonance imaging-based personalized heart digital twins may overcome these challenges by noninvasively predicting VT circuits and optimum ablation lesion sites. In this combined clinical and digital twin study, we investigated the relationship between digital twin-predicted VTs and optimum ablation lesion sets with their invasively mapped counterparts during clinical VT ablation.

Despite current treatment strategies for atherosclerotic vascular disease focusing on lifestyle modification and lowering cholesterol, a significant residual risk of major atherosclerotic complication remains, prompting investigation into lipoprotein(a) (Lp(a)) as a potential predictive biomarker. The objective of this study was to determine the usefulness of Lp(a) in identifying patients at high risk of incident extracoronary atherosclerotic vascular disease and complications.

Efforts to enhance risk stratification in patients with coronary artery disease have driven the pursuit of early detection of rupture-prone plaques-before destabilization and the onset of life-threatening thrombosis-giving rise to the concept of the vulnerable plaque (VP). Invasive diagnostic modalities closely mirror histology and provide instrumental information on VP hallmarks and their prognostic significance. However, limited positive predictive value and invasive nature restrict their use for systematic screening. Noninvasive techniques offer broader application potential, but their specificity and resolution remain inferior to those of invasive techniques. A deeper understanding of the complex interplay between traditional ischemic risk factors, anatomic settings, rheological effects and systemic influences contributing to plaque evolution and rupture has refined our approach to identifying and managing VPs. Systemic therapies have been shown to counteract plaque progression and stabilize VPs by thickening the fibrous cap, decreasing atheroma and necrotic core volumes, and reducing inflammation. In parallel, the hypothesis of sealing and passivating VPs by intravascular imaging-guided preventive stenting is gaining support after the promising results of clinical trials and substantial advances in contemporary device performance and biocompatibility. Upcoming evidence will be instrumental in defining the net benefit of novel diagnostic tools and therapeutic strategies for VPs.

Cardiovascular disease remains the leading cause of death worldwide, calling for the development of novel therapeutics. Over the past 3 decades, substantial investments in human genetic research have unveiled the genetic architecture of cardiovascular disease, offering promising novel therapeutic targets. These discoveries have been instrumental in the development of several cardiovascular drug development programs, such as those targeting proprotein convertase subtilisin/kexin type 9, lipoprotein (a), apo C3, and angiopoietin-like 3. Large-scale resources such as population-based biobanks and data repositories, now enable human genetic data to be leveraged at scale and inform not only target selection, but also clinical drug development. This review highlights the transformative potential of human genetics in cardiovascular drug development, focusing on IL (interleukin)-6 signaling as a case study. Specifically, we discuss how IL-6 signaling was pinpointed as a key causal mediator of atherosclerosis by genetic data, shaping the current development landscape for anti-IL-6 therapeutics in cardiovascular disease. Recent genetic studies employing innovative methodologies have provided key insights into prioritizing indications for clinical testing, informing repurposing strategies, optimizing clinical trial design for population selection, and assessing safety signals. Despite this progress, methodological challenges, such as pleiotropic effects of genetic variants, extrapolation of small genetic associations to large interventional effects, and the predominance of European-derived data, highlight the need for careful interpretation. Continued methodological advances, coupled with the emergence of high-throughput omics data and detailed cardiovascular phenotyping, promise unprecedented opportunities to refine drug discovery and development.