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Background: Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data. Methods: 2,187 patients admitted to five UK hospitals with a diagnosis of HF and a left ventricular ejection fraction ≥ 40% were identified from the NIHR Health Informatics Collaborative database. Partition-based, model-based, and density-based machine learning clustering techniques were applied. Cox Proportional Hazards and Fine-Gray competing risks models were used to compare outcomes (all-cause mortality and hospitalisation for HF) across phenogroups. Results: Three phenogroups were identified: (1) Younger, predominantly female patients with high prevalence of cardiometabolic and coronary disease; (2) More frail patients, with higher rates of lung disease and atrial fibrillation; (3) Patients characterised by systemic inflammation and high rates of diabetes and renal dysfunction. Survival profiles were distinct, with an increasing risk of all-cause mortality from phenogroups 1 to 3 (p < 0.001). Phenogroup membership significantly improved survival prediction compared to conventional factors. Phenogroups were not predictive of hospitalisation for HF. Conclusions: Applying unsupervised machine learning to routinely collected electronic health record data identified phenogroups with distinct clinical characteristics and unique survival profiles. [ABSTRACT FROM AUTHOR]

Aims: Population‐wide, person‐level, linked electronic health record data are increasingly used to estimate epidemiology, guide resource allocation, and identify events in clinical trials. The accuracy of data from NHS Digital (now part of NHS England) for identifying hospitalization for heart failure (HHF), a key HF standard, is not clear. This study aimed to evaluate the accuracy of NHS Digital data for identifying HHF. Methods and results: Patients experiencing at least one HHF, as determined by NHS Digital data, and age‐ and sex‐matched patients not experiencing HHF, were identified from a prospective cohort study and underwent expert adjudication. Three code sets commonly used to identify HHF were applied to the data and compared with expert adjudication (I50: International Classification of Diseases‐10 codes beginning I50; OIS: Clinical Commissioning Groups Outcomes Indicator Set; and NICOR: National Institute for Cardiovascular Outcomes Research, used as the basis for the National Heart Failure Audit in England and Wales). Five hundred four patients underwent expert adjudication, of which 10 (2%) were adjudicated to have experienced HHF. Specificity was high across all three code sets in the first diagnosis position {I50: 96.2% [95% confidence interval (CI) 94.1–97.7%]; NICOR: 93.3% [CI 90.8–95.4%]; OIS: 95.6% [CI 93.3–97.2%]} but decreased substantially as the number of diagnosis positions expanded. Sensitivity [40.0% (CI 12.2–73.8%)] and positive predictive value (PPV) [highest with I50: 17.4% (CI 8.1–33.6%)] were low in the first diagnosis position for all coding sets. PPV was higher for the National Heart Failure Audit criteria, albeit modestly [36.4% (CI 16.6–62.2%)]. Conclusions: NHS Digital data were not able to accurately identify HHF and should not be used in isolation for this purpose. [ABSTRACT FROM AUTHOR]

This article, published in the Oxford Medical Case Reports, presents a case of a 49-year-old Caucasian male with left ventricular noncompaction cardiomyopathy (LVNC). The patient had severe left ventricular dilation and dysfunction, leading to a referral for transplant assessment. However, as he was asymptomatic on medical therapy, he was discharged to local heart failure services. The patient later developed a large left ventricular thrombus, which led to multi-organ failure and an embolic stroke. Treatment was ultimately withdrawn due to the contraindication for transplant. The article discusses the clinical sequalae of LVNC and the controversy surrounding prophylactic anticoagulation. [Extracted from the article]

Background: Studies predating widespread COVID-19 vaccination identified patients with congenital heart disease (CHD) as a group at increased risk of severe outcomes from COVID-19. Here we evaluate the impact of vaccination on COVID-19 outcomes among patients with CHD., Methods: We conducted a case-control study using linked English electronic health records (n=3 18 135). Patients with CHD were matched with controls by age, sex, ethnicity and GP practice. The 'prevaccination' cohort comprised unvaccinated patients with CHD and matched controls with first-recorded SARS-CoV-2 infection between 1 March and 8 December 2020 (7805 cases, 27 620 controls). The 'post-vaccination' cohort comprised vaccinated patients with CHD and matched controls with first-recorded SARS-CoV-2 infection between 1 March 2021 and 1 April 2022, at least 14 days after vaccination (57 550 cases, 225 160 controls). Odds of severe COVID-19 outcomes were compared using conditional logistic regression. We also compared the rate at which vaccine efficacy diminished, and the incidence of vaccine-associated complications., Results: Compared with the prevaccination cohort, postvaccination patients with CHD exhibited markedly reduced rates of COVID-19-related hospitalisation (0.5% vs 15.8%) and mortality rates (0.5% vs 4.6%). Compared with vaccinated controls, vaccinated patients with CHD remained at increased risk of hospitalisation (0.5% vs 0.2%, adjusted OR 2.24 (1.88-2.65); p<0.001) and death (0.5% vs 0.3%, adjusted OR 1.81 (1.54-2.13); p<0.001). There was no evidence that vaccine efficacy declined faster in patients with CHD, or that patients with CHD experienced a larger increase in incidence of myocarditis, pericarditis or thrombotic events., Conclusion: We observed a lower absolute risk of hospitalisation and death from COVID-19 in CHD patients after vaccination. However, in vaccinated CHD patients, an elevated risk of severe outcomes persists compared with vaccinated people without CHD. These results emphasise the importance of vaccination in the CHD population, and of vigilance among care providers dealing with COVID-19 infection in CHD patients, even if fully vaccinated., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The mitoribosome synthesizes 13 protein subunits of the oxidative phosphorylation system encoded by the mitochondrial genome. The mitoribosome is composed of 12S rRNA, 16S rRNA and 82 mitoribosomal proteins encoded by nuclear genes. To date, variants in 12 genes encoding mitoribosomal proteins are associated with rare monogenic disorders, and frequently show combined oxidative phosphorylation deficiency. Here, we describe five unrelated individuals with biallelic variants in the DAP3 nuclear gene encoding mitoribosomal small subunit 29 (MRPS29), with variable clinical presentations ranging from Perrault syndrome (sensorineural hearing loss and ovarian insufficiency) to an early childhood neurometabolic phenotype. Assessment of respiratory chain function and proteomic profiling of fibroblasts from affected individuals demonstrated reduced MRPS29 protein levels, and consequently decreased levels of additional protein components of the mitoribosomal small subunit, associated with a combined complex I and IV deficiency. Lentiviral transduction of fibroblasts from affected individuals with wild-type DAP3 cDNA increased DAP3 mRNA expression, and partially rescued protein levels of MRPS7, MRPS9 and complex I and IV subunits, demonstrating the pathogenicity of the DAP3 variants. Protein modelling suggested that DAP3 disease-associated missense variants can impact ADP binding, and in vitro assays demonstrated DAP3 variants can consequently reduce both intrinsic and extrinsic apoptotic sensitivity, DAP3 thermal stability and DAP3 GTPase activity. Our study presents genetic and functional evidence that biallelic variants in DAP3 result in a multisystem disorder of combined oxidative phosphorylation deficiency with pleiotropic presentations, consistent with mitochondrial dysfunction., Competing Interests: Declaration of interest The authors declare no competing interests.