Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho.

Daily calorie restriction (CR) and intermittent fasting (IF) enhance longevity and cognition but the effects and mechanisms that differentiate these two paradigms are unknown. We examined whether IF in the form of every-other-day feeding enhances cognition and adult hippocampal neurogenesis (AHN) when compared to a matched 10% daily CR intake and ad libitum conditions. After 3 months under IF, female C57BL6 mice exhibited improved long-term memory retention. IF increased the number of BrdU-labeled cells and neuroblasts in the hippocampus, and microarray analysis revealed that the longevity gene Klotho (Kl) was upregulated in the hippocampus by IF only. Furthermore, we found that downregulating Kl in human hippocampal progenitor cells led to decreased neurogenesis, whereas Kl overexpression increased neurogenesis. Finally, histological analysis of Kl knockout mice brains revealed that Kl is required for AHN, particularly in the dorsal hippocampus. These data suggest that IF is superior to 10% CR in enhancing memory and identifies Kl as a novel candidate molecule that regulates the effects of IF on cognition likely via AHN enhancement.

The frequency of gene variant reclassification and its impact on clinical management in the inherited arrhythmia clinic.

BACKGROUND: Genetic testing in the inherited arrhythmia clinic informs risk stratification, clinical management, and family screening. Periodic review of variant classification is recommended as supporting evidence accrues over time. However, there is limited reporting of real-world data on the frequency and impact of variant reclassification. OBJECTIVE: The purpose of this study was to determine the burden of variant reclassification in our inherited arrhythmia clinic and the impact on clinical management. METHODS: Genetic testing reports for patients referred to our clinic from 2004-2020 were reviewed. Reported variants were reinvestigated using ClinVar, VarSome, and a literature review. Classification was updated using the American College of Medical Genetics and Genomics (ACMG) criteria and tested for association with arrhythmic events and modification of medical management. RESULTS: We identified 517 patients (median age 37 years) who underwent gene panel testing. A variant of uncertain significance (VUS) was reported for 94 patients (18.2%) and more commonly identified when using large gene panels (P <.001). A total of 28 of 87 unique VUSs (32.2%) were reclassified to pathogenic/likely pathogenic (n = 11) or benign/likely benign (n = 17). Of 138 originally reported pathogenic variants, 7 (5.1%) lacked support using ACMG criteria. Variant reclassification was not associated with arrhythmic events; however, it did impact genotype-specific counseling and future therapeutic options. CONCLUSION: In our large real-world patient cohort, we identify a clinically important proportion of both pathogenic variants and VUSs with evidence for reclassification. These findings highlight the need for informed pretest counseling, a regular structured review of variants reported in genetic testing, and the potential benefits to patients for supporting genotype-guided therapy.

Association of Longer Leukocyte Telomere Length With Cardiac Size, Function, and Heart Failure.

Importance: Longer leukocyte telomere length (LTL) is associated with a lower risk of adverse cardiovascular outcomes. The extent to which variation in LTL is associated with intermediary cardiovascular phenotypes is unclear. Objective: To evaluate the associations between LTL and a diverse set of cardiovascular imaging phenotypes. Design, Setting, and Participants: This is a population-based cross-sectional study of UK Biobank participants recruited from 2006 to 2010. LTL was measured using a quantitative polymerase chain reaction method. Cardiovascular measurements were derived from cardiovascular magnetic resonance using machine learning. The median (IQR) duration of follow-up was 12.0 (11.3-12.7) years. The associations of LTL with imaging measurements and incident heart failure (HF) were evaluated by multivariable regression models. Genetic associations between LTL and significantly associated traits were investigated by mendelian randomization. Data were analyzed from January to May 2023. Exposure: LTL. Main Outcomes and Measures: Cardiovascular imaging traits and HF. Results: Of 40 459 included participants, 19 529 (48.3%) were men, and the mean (SD) age was 55.1 (7.6) years. Longer LTL was independently associated with a pattern of positive cardiac remodeling (higher left ventricular mass, larger global ventricular size and volume, and higher ventricular and atrial stroke volumes) and a lower risk of incident HF (LTL fourth quartile vs first quartile: hazard ratio, 0.86; 95% CI, 0.81-0.91; P = 1.8 × 10-6). Mendelian randomization analysis suggested a potential causal association between LTL and left ventricular mass, global ventricular volume, and left ventricular stroke volume. Conclusions and Relevance: In this cross-sectional study, longer LTL was associated with a larger heart with better cardiac function in middle age, which could potentially explain the observed lower risk of incident HF.

Animation-supported consent for urgent angiography and angioplasty: a service improvement initiative.

OBJECTIVE: Patient understanding of angiography and angioplasty is often incomplete at the time of consent. Language barriers and time constraints are significant obstacles, particularly in the urgent setting. We introduced digital animations to support consent and assessed the effect on patient understanding. METHODS: Multi-language animations explaining angiography and angioplasty (www.explainmyprocedure.com/heart) were introduced at nine district hospitals for patients with acute coronary syndrome before urgent transfer to a cardiac centre for their procedure. Reported understanding of the reason for transfer, the procedure, its benefits and risks in 100 consecutive patients were recorded before introduction of the animations into practice (no animation group) and in 100 consecutive patients after their introduction (animation group). Patient understanding in the two groups was compared. RESULTS: Following introduction, 83/100 patients reported they had watched the animation before inter-hospital transfer (3 declined and 14 were overlooked). The proportions of patients who understood the reason for transfer, the procedure, its benefits and risks in the no animation group were 58%, 38%, 25% and 7% and in the animation group, 85%, 81%, 73% and 61%, respectively. The relative improvement (ratio of proportions) was 1.5 (95% CI 1.2 to 1.8), 2.1 (1.6 to 2.8), 2.9 (2.0 to 4.2) and 8.7 (4.2 to 18.1), respectively (p<0.001 for all comparisons). CONCLUSION: Use of animations explaining angiography and angioplasty is feasible before urgent inter-hospital transfer and was associated with substantial improvement in reported understanding of the procedure, its risks and its benefits. The approach is not limited to cardiology and has the potential to be applied to all specialties in medicine.

Paired surveys for patients and physiologists in echocardiography: a single-centre experience.

The British Society of Echocardiography (BSE) highlights the importance of patient questionnaires as part of the quality improvement process, To this end, we implemented a novel system whereby paired surveys were completed by patients and physiologists for transthoracic echocardiography scans, allowing for parallel comparison of the experiences of service providers and end users. Anonymised questionnaires were completed for each scan by the patient and physiologist for outpatient echocardiographic scans in a teaching hospital. In 26% of the responses, patient found the scans at least slightly painful, and in 24% of scans physiologists were in discomfort. The most common reason given by physiologists for technically difficult or inadequate scans was patient discomfort. In 38% of the scans at least one person (the patient or the physiologist) was in at least some discomfort. Comparative data showed that the scans reported as most painful by patients were also reported by the physiologists as difficult and uncomfortable. In summary, these results demonstrate the feasibility of implementing paired surveys. Patient information leaflets by the BSE and National Health Service (NHS) describe echocardiography as painless but the results here indicate this is not always the case.