Background Structural and electrophysiological remodeling characterize heart failure (HF) enhancing arrhythmias. PKD1 (protein kinase D1) is upregulated in HF and mediates pathological hypertrophic signaling, but its role in K+ channel remodeling and arrhythmogenesis in HF is unknown. Methods and Results We performed echocardiography, electrophysiology, and expression analysis in wild‐type and PKD1 cardiomyocyte‐specific knockout (cKO) mice following transverse aortic constriction (TAC). PKD1‐cKO mice exhibited significantly less cardiac hypertrophy post‐TAC and were protected from early decline in cardiac contractile function (3 weeks post‐TAC) but not the progression to HF at 7 weeks post‐TAC. Wild‐type mice exhibited ventricular action potential duration prolongation at 8 weeks post‐TAC, which was attenuated in PKD1‐cKO, consistent with larger K+ currents via the transient outward current, sustained current, inward rectifier K+ current, and rapid delayed rectifier K+ current and increased expression of corresponding K+ channels. Conversely, reduction of slowly inactivating K+ current was independent of PKD1 in HF. Acute PKD inhibition slightly increased transient outward current in TAC and sham wild‐type myocytes but did not alter other K+ currents. Sham PKD1‐cKO versus wild‐type also exhibited larger transient outward current and faster early action potential repolarization. Tachypacing‐induced action potential duration alternans in TAC animals was increased and independent of PKD1, but diastolic arrhythmogenic activities were reduced in PKD1‐cKO. Conclusions Our data indicate an important role for PKD1 in the HF‐related hypertrophic response and K+ channel downregulation. Therefore, PKD1 inhibition may represent a therapeutic strategy to reduce hypertrophy and arrhythmias; however, PKD1 inhibition may not prevent disease progression and reduced contractility in HF.

The non-invasive prenatal test (NIPT) is a highly sensitive blood analysis tool that allows for the early detection of multiple chromosomal abnormalities, including Down syndrome. Prenatal testing in general and a positive test outcome in particular leave pregnant parents facing difficult ethical decisions and life-changing dilemmas. The language used by medical practitioners in this context has the potential to exert a strong influence on parents in their decision-making process. During counseling, health care professionals (HCPs) are expected to encourage parents to make an informed yet autonomous decision, which hinges on maximally unbiased, clear and consistent communication from the HCP. It is still unclear whether medical students are aware of this importance of unbiased communication, how they perceive the role of HCPs in the prenatal counseling process, and what perspectives they have regarding the disabilities screened for. Our research project aims to address this gap, presenting the results of a transdisciplinary survey completed by 245 medical students at KU Leuven. In particular, the survey investigates: (1) the students' view on the ideal prenatal counseling process; (2) their knowledge of NIPT and Down syndrome (the most prevalent disability NIPT screens for); and (3) their general attitudes towards disabilities. Results reveal that more than 50% of medical students do not feel prepared for genetic counseling. The survey further shows a lack of knowledge and some clearly negative attitudes towards life with disability; 20% of medical students agree that a life with Down syndrome should be avoided. Overall, results indicate fairly heterogeneous distribution of knowledge and fairly diverse attitudes of the students, suggesting revisions in the current curriculum might be needed to increase the homogeneity towards counseling and disabilities in the medical student population.

No abstract