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Euan Ashley

Publications and source records attributed to Euan Ashley.

4 recordsLinked to original sources
PubMed2026

RBM20 Truncating Variants and Human Cardiomyopathy.

IMPORTANCE: Genetic diagnosis has become increasingly important to guide clinical decision-making for patients with dilated cardiomyopathy (DCM). Pathogenic or likely pathogenic (P/LP) missense variants in the gene RBM20 cause a highly penetrant arrhythmogenic DCM, but the role of RBM20 truncating variants (RBM20tvs) is unclear. OBJECTIVE: To assess the contribution of RBM20 variants to arrhythmogenic DCM. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, participants in the genome-first UK Biobank (UKB) and All of Us populations were evaluated to assess the etiologic fraction, natural history and penetrance of RBM20 variants. Retrospective data were collected from an international cohort of patients with DCM and RBM20 variants identified at centers of excellence for genetic heart disease and compared based on time to event. Study dates are not disclosed because the institutional review board did not authorize the sharing of this information. EXPOSURES: RBM20 variants were compared to known P/LP variants and variants of uncertain significance in RBM20 as well as titin truncating variants (TTNtvs). MAIN OUTCOMES AND MEASURES: Major ventricular arrhythmias, end-stage heart failure, and heart failure hospitalization as measured by medical record review (retrospective cohort) and diagnostic codes (UKB). RESULTS: Two main cohorts were studied for this project. In UK Biobank, a cohort of participants with RBM20tvs, RBM20 synonymous variants, and TTNtvs was studied. Of these 4249 participants, 1869 (44%) were male. The mean (SD) age at enrollment was 56 (8.2) years. In the RBM20 registry, of 179 patients, 105 (58.6%) were male, and the mean (SD) age at enrollment was 43.8 (19.1) years. A validation cohort from the All of Us biobank was also used. This consisted of 7002 participants, 4342 of whom (62.0%) were male, and the mean (SD) age was 52.7 (16.7) years. The etiologic fraction of RBM20 variants in arrhythmogenic DCM was 0.53 (95% CI, 0.32-0.67; P&#x2009;<&#x2009;.001). In genome-first biobanks, lifetime incidence of cardiomyopathy, heart failure, or major ventricular arrhythmia diagnosis was lower in participants with RBM20 variants than in those with TTNtvs (hazard ratio, 0.55; 95% CI, 0.36-0.84; P&#x2009;<&#x2009;.001). Patients with RBM20tvs and DCM presented to referral centers later in life than those with P/LP RBM20 and DCM (mean [SD], 53 [10] vs 34 [18] years; P&#x2009;<&#x2009;.001) and were less likely to have a family history of sudden cardiac arrest (2 of 10 [20%] vs 11 of 17 [65%]; P&#x2009;=&#x2009;.046) or cardiomyopathy (2 of 10 [20%] vs 14 of 18 [78%]; P&#x2009;<&#x2009;.001). There was no significant difference in age- and sex-adjusted incident major heart failure or arrhythmia events between patients with RBM20tv and DCM or those with P/LP RBM20 and DCM, though sex-adjusted lifetime hazard was reduced in those with RBM20tv and DCM (hazard ratio, 0.13; 95% CI, 0.03-0.56; P&#x2009;=&#x2009;.01). CONCLUSIONS AND RELEVANCE: This study found that RBM20 variants contributed to arrhythmogenic DCM phenotypes but conferred reduced lifetime disease penetrance compared to TTNtvs and milder disease severity alone than P/LP RBM20 variants. Their potential for additive interactions with other damaging variants should be considered in patients with DCM and their families.

Humans↗
PubMed2002

Exercise testing scores as an example of better decisions through science.

INTRODUCTION: The application of common statistical techniques to clinical and exercise test data has the potential to become a useful tool for assisting in the diagnosis of coronary artery disease, assessing prognosis, and reducing the cost of evaluating patients with suspected coronary disease. Since general practitioners function as gatekeepers and decide which patients must be referred to the cardiologist, they need to optimally use the basic tools they have available (i.e., history, physical exam, and the exercise test). METHODS: Review of the literature with a focus on the scientific techniques for aiding the decision-making process. RESULTS: Scores derived from multivariable statistical techniques considering clinical and exercise data have demonstrated superior discriminating power when compared using receiver-operating-characteristic curves with the ST segment response. In addition, by stratifying patients as to probability of disease and prognosis, they provide a management strategy. While computers as part of information management systems can calculate complicated equations to provide scores, physicians are reluctant to trust them. Thus, these scores have been represented as nomograms or simple additive tables so physicians are comfortable with their application. Scores have also been compared with physician judgment and been found to estimate the presence of coronary disease and prognosis as well as expert cardiologists, and often better than nonspecialists. CONCLUSION: Multivariate scores can empower the clinician to assure the cardiac patient with access to appropriate and cost-effective cardiological care.

Adult↗
PubMedDate not supplied

Better decisions through science: exercise testing scores.

Statistical tools can be used to create scores for assisting in the diagnosis of coronary artery disease and assessing prognosis. General practitioners and internists frequently function as gatekeepers, deciding which patients must be referred to the cardiologist. Therefore, they need to use the basic tools they have available (ie, history, physical examination and the exercise test) in an optimal fashion. Scores derived from multivariable statistical techniques considering clinical and exercise data have demonstrated superior discriminating power compared with diagnosis only using the ST segment response. In addition, by stratifying patients as to probability of disease and prognosis, they provide a more practical management strategy than a response of normal or abnormal. Although computers, as part of information management systems, can calculate complicated equations and derive these scores, physicians are reluctant to trust them. However, when represented as nomograms or simple additive discrete pieces of information, scores are more readily accepted. The scores have been compared with physician judgment and have been found to estimate the presence of coronary disease and prognosis as well as expert cardiologists and often better than nonspecialists. However, the discriminating power of specific variables from the medical history and exercise test remains unclear because of inadequate study design and differences in study populations. Should expired gases be substituted for estimated METs? Should ST/heart rate index be used instead of putting ST depression and heart rate separately into the models? Should right-sided chest leads and heart rate in recovery be considered? There is a need for further evaluation of these easily obtained variables to improve the accuracy of prediction algorithms, especially in women. The portability and reliability of scores must be ensured because access to specialized care must be safeguarded. Assessment of the clinical and exercise test data and application of the newer scores can empower the clinician to assure the cardiac patient access to appropriate and cost-effective cardiologic care.

Age Factors↗