The introduction of proprotein convertase subtilisin/Kexin type 9 (PSCK9) inhibitors has transformed the approach to low-density lipoprotein cholesterol lowering in the prevention of atherosclerotic cardiovascular disease. This paper aims to determine the longer-term impact of these interventions on major adverse cardiovascular events (MACE) and all-cause mortality. A systematic search of major databases was conducted to identify randomised controlled trials comparing PCSK9 inhibitors with a placebo. Studies were included if they reported cardiovascular events with a follow-up duration greater than 12 months. Frequentist, Bayesian meta-analysis, and trial sequential analysis were utilised to assess the efficacy of PCSK9 inhibitors in reducing MACE. Amongst 11 studies encompassing 52,372 patients, statistically significant reductions were observed in rates of myocardial infarction (risk ratio (RR) 0.78; 95% confidence interval (CI) 0.68 to 0.89, p < 0.01, I2 = 20%), coronary revascularisation (RR 0.83; 95% CI 0.75 to 0.91, p < 0.01, I2 = 9.1%) and ischemic stroke (RR 0.76; 95% CI 0.66 to 0.87, p < 0.01, I2 = 0%) amongst patients on PCSK9 inhibitors compared to placebo based on random-effects meta-analysis. Trial sequential analysis and Bayesian analysis supported these results, with posterior probabilities that PCSK9 inhibitors improve outcomes for myocardial infarction, coronary revascularisation, and ischemic stroke of 83.8%, 82.9%, and 69.4%, respectively. No statistically significant effect was observed for the other outcomes. This meta-analysis demonstrates significant reductions in the rate of myocardial infarction, coronary revascularisation, and ischemic stroke. Further benefits may emerge with longer-term follow-up and alternate methods of targeting PCSK9.
Mechanotransduction is essential for cardiovascular physiology, enabling cells to sense and respond to mechanical forces such as shear stress, stretch, pressure, and extracellular matrix deformation. Among mechanosensitive ion channels, PIEZO1 and PIEZO2 have emerged as critical regulators of cardiovascular mechanobiology. These large trimeric ion channels convert mechanical stimuli into calcium-dependent electrochemical signals that regulate vascular development, endothelial homeostasis, cardiac remodeling, inflammatory activation, and blood pressure control. Recent advances in structural biology, electrophysiology, and molecular genetics have substantially improved understanding of PIEZO channel architecture, mechanogating mechanisms, and downstream signaling pathways. In the cardiovascular system, PIEZO1 functions prominently in endothelial cells, cardiomyocytes, fibroblasts, erythrocytes, and vascular smooth muscle cells, where dysregulated signaling contributes to hypertension, fibrosis, cardiac hypertrophy, ischemic injury, and vascular inflammation. This review summarizes current knowledge of PIEZO-mediated cardiovascular mechanotransduction, emphasizing structural mechanisms, physiological functions, disease implications, and therapeutic potential. Emerging computational approaches, including artificial intelligence and machine learning-assisted electrophysiology, are also discussed as promising tools for advancing mechanobiological research, multiscale modeling, and precision cardiovascular medicine.
Hypertension affects many patients worldwide, and its precise treatment is the focus of clinical research. Currently, conventional clinical methods for monitoring blood pressure can only intermittently measure systolic and diastolic blood pressure and cannot monitor important hemodynamic parameters such as cardiac output (CO), systemic vascular resistance (SVR), and arterial elasticity, thereby affecting the formulation of individualized treatment plans. In recent decades, the emergence of non-invasive hemodynamic monitoring methods has addressed these clinical challenges. These methods use non-invasive methods to monitor parameters such as cardiac pumping function, vascular resistance, and volume status, helping clinicians better understand the pathophysiology of hypertension and facilitating a shift from “empirical blood pressure reduction” to “precision treatment based on hemodynamics”. This article aims to introduce the technical principles, main parameters, and clinical applications of non-invasive hemodynamic monitoring, with a focus on discussing its clinical value in hypertension classification, formulation of individualized treatment plans, assessment of treatment effects, and management of special populations. Based on this, future application and development directions are proposed, aiming to provide references and evidence for the clinical practice of precise hypertension treatment.
Sepsis remains the leading cause of acute respiratory distress syndrome (ARDS) and cardiovascular dysfunction in the ICU. Sepsis-induced cardiomyopathy (SCM) and sepsis-associated ARDS frequently coexist and share overlapping mechanisms, including cytokine-driven injury, endothelial disruption, microvascular dysfunction, and mitochondrial abnormalities. Despite their clinical relevance, these entities are often evaluated in isolation, overlooking the integrated heart-lung interactions that characterize severe sepsis and ARDS. This narrative review synthesizes current evidence on the shared pathophysiology and diagnostic approach to cardiomyopathy and lung injury in sepsis-associated ARDS, emphasizing the physiologic links that unify these syndromes. We review the immunologic, endothelial, and metabolic mechanisms that drive concurrent myocardial depression and alveolocapillary injury, with particular attention to microcirculatory failure, autonomic dysregulation, and mechanical ventilation-associated cardiopulmonary interactions. We then review diagnostic tools, including echocardiography, lung ultrasound, CT imaging, biomarkers, and advanced hemodynamic monitoring, and highlight the impact of integrated assessment on accurate phenotyping and management. Cardiomyopathy and ARDS in sepsis arise from common pathophysiologic drivers and should be understood as a unified cardiopulmonary phenotype rather than isolated organ failures. Early multimodal detection is critical for optimizing management strategies and improving outcomes.
As an anesthetic agent, etomidate provides profound hemodynamic stability, superior to propofol even when it is dose reduced. However, its use has been curtailed due to concerns regarding adrenal cortical suppression demonstrated clinically in the setting of prolonged infusion for sedation in the intensive care unit. In addition, etomidate reproducibly results in significant myoclonus when employed in the absence of other pharmacology. Recently, utilizing both pharmacokinetic and pharmacodynamic considerations, a number of etomidate analogs have been developed that retain the favorable properties of their parent agent, including rapid onset of hypnosis and rapid recovery, amnesia, and cardiovascular stability, but do not result in inhibition of steroidogenesis. A few of these analogs have now entered clinical trials and are poised to transform acute care and anesthesia for critically ill patients.
Aortic aneurysm (AA) is a life-threatening vascular disease characterized by progressive aortic dilatation, wall degeneration, and risk of rupture. Although diameter-based imaging remains central to clinical decision-making, it does not fully reflect the biological processes underlying aneurysm initiation, expansion, and rupture. Recent advances in omics, vascular biology, functional imaging, and nanomedicine provide new opportunities to reinterpret AA pathogenesis. In this review, we propose the Four-Hit Hypothesis as an integrative framework for understanding AA progression. The four hits include disruption of the aortic barrier environment, immune-inflammatory invasion, maladaptive proliferative repair, and aging-associated structural destruction. We discuss their roles across disease stages, the differences between abdominal and thoracic aortic aneurysms, and their implications for biomarkers, imaging, and therapeutic development. This review aims to organize current evidence on AA biology and highlight potential directions for future studies in risk assessment, imaging, and targeted intervention.
