Hydroquinidine 300mg modified-release capsules

Background: Short QT syndrome (SQTS) is a rare inheritable channelopathy characterized by a shortened corrected QT interval on an electrocardiogram and a significant risk of atrial and ventricular arrhythmias, potentially leading to sudden cardiac death. Despite advancements in our understanding of SQTS, knowledge gaps persist due to its extreme rarity. This scoping review aims to summarize the available knowledge on its clinical presentations, genetic mutations, and management strategies, while identifying areas for further investigation. Methods: This scoping review was conducted across the PubMed, Scopus, and Cochrane databases and identified relevant case reports, case series, and available studies on SQTS. We focused on articles that reported clinical outcomes, genetic mutations, diagnostic criteria, and management strategies, while excluding studies on the secondary causes of short QT intervals. Results: SQTS is present across a wide age range, from asymptomatic individuals to those experiencing syncope, palpitations, or sudden cardiac arrest. Common genetic mutations include KCNQ1, KCNH2, and KCNJ2. Management strategies vary, with some patients receiving implantable cardioverter defibrillators for secondary prevention and others treated pharmacologically, primarily with hydroquinidine. Our findings highlight the rarity and clinical variability of SQTS, underscoring the need for optimized diagnostic criteria and individualized management strategies. Conclusions: This review emphasizes the need for continued research to better understand the genetic basis of SQTS, optimize diagnostic tools, and improve treatment approaches. Large-scale studies and the integration of genetic and clinical data are critical to addressing the gaps in SQTS management and improving outcomes for patients with this potentially life-threatening arrhythmic disorder.

Abstract licence: CC BY

Colon cancer remains a leading cause of cancer-related deaths, and drug repurposing offers a promising strategy to identify new therapies. Hydroquinidine (HQ), a class I antiarrhythmic agent, has recently been suggested to possess anticancer properties; however, its preclinical safety and efficacy in colorectal cancer are not well defined. The safety of HQ was evaluated in Wistar rats following OECD guidelines. Rats received daily intraperitoneal doses (2.5–25 mg/kg) for 90 days, with hematological, biochemical, and histopathological assessments performed. HQ was well tolerated up to 12.5 mg/kg, whereas 25 mg/kg caused signs of hepatotoxicity without lethality. A 1,2-dimethylhydrazine-induced colorectal cancer model was then used to assess HQ at safe doses (6.25 and 12.5 mg/kg) compared with cisplatin. Tissue histopathology and selected molecular markers associated with inflammation, apoptosis, epithelial–mesenchymal transition, and PI3K/AKT/mTOR pathway activity were analyzed. In the DMH-induced colon cancer model, HQ improved colonic tissue architecture and was associated with lower histopathological scores compared with untreated tumor controls. HQ also modulated tumor-associated markers by reducing IL-6 immunoreactivity, increasing caspase-3 expression, enhancing E-cadherin immunoreactivity, and decreasing vimentin expression. Moreover, HQ was associated with reduced immunoreactivity of mTOR pathway-related markers, suggesting attenuation of pathway activation in this experimental context. Overall, HQ showed an acceptable safety profile at the selected doses and exerted favorable histopathological and molecular modulatory effects, supporting further investigation as a potential repurposing candidate.

Abstract licence: CC BY 4.0