Single-Cell RNA Sequencing Reveals Cardiac Fibroblast-Specific Transcriptomic Changes in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common cause of heart failure, with a complex aetiology involving multiple cell types. We aimed to detect cell-specific transcriptomic alterations in DCM through analysis that leveraged recent advancements in single-cell analytical tools. Single-cell RNA sequencing (scRNA-seq) data from human DCM cardiac tissue were subjected to an updated bioinformatic workflow in which unsupervised clustering was paired with reference label transfer to more comprehensively annotate the dataset. Differential gene expression was detected primarily in the cardiac fibroblast population. Bulk RNA sequencing was performed on an independent cohort of human cardiac tissue and compared with scRNA-seq gene alterations to generate a stratified list of higher-confidence, fibroblast-specific expression candidates for further validation. Concordant gene dysregulation was confirmed in TGFß-induced fibroblasts. Functional assessment of gene candidates showed that AEBP1 may play a significant role in fibroblast activation. This unbiased approach enabled improved resolution of cardiac cell-type-specific transcriptomic alterations in DCM.

Alcohol consumption and progression of heart failure in those at risk for or with pre-heart failure.

BACKGROUND: This study aims to understand the dose-response relationship between alcohol consumption, progression of left ventricular dysfunction (LVD) and/or symptomatic heart failure (HF) in an older European population at risk for HF (stage A) or with pre-HF (stage B). METHODS: This longitudinal, observational, secondary analysis of the St Vincent's Screening TO-Prevent Heart Failure (STOP-HF) follow-up study, excluded former alcohol drinkers and included patients with documented alcohol intake and echocardiography at baseline and follow up ≥18 months. It evaluated the relationship between alcohol intake and progression of LVD/symptomatic (stage C) HF in those at risk for or with pre-HF. RESULTS: Of 744 patients (mean age 66.5 [SD 9.8] years), 395 (53.1%) were female, and 260 (34.9%) had pre-HF at baseline. Overall, 201 (27.0%) patients reported no alcohol usage, 356 (47.8%) reported ≤70g/wk (low) alcohol intake and 187 (25.1%) reported >70g/wk (moderate-high). Over a median follow up of 5.44 [IQR 4.33;6.73] years, 84 (11.3%) patients had progression of LVD/symptomatic HF. Alcohol usage of >70g/wk was associated with an adjusted 4.9-fold (95% CI 1.7- 15.1, p<0.01) increased risk of HF progression amongst those with pre-HF at baseline. The adverse relationship remained significant when adjusting for age, sex, diabetes, hypertension, body mass index, as well as further models with baseline liver function and alcohol dehydrogenase 1B gene variant rs1229984 status. The association remained when excluding those with high (>140g) weekly alcohol intake. In patients at risk for HF there was no association of alcohol usage with progression of LVD/symptomatic HF. No protective associations of low alcohol usage (≤70g/wk) on progression of HF were found. CONCLUSION: Moderate to high alcohol (>70g/wk) usage appears to be associated with progression of LVD/symptomatic HF in those with pre-HF and we did not observe protective benefits of low alcohol usage.

A pilot study of the quality of care of atrial fibrillation in Irish general practice.

BACKGROUND: Worldwide, atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults and poses a significant burden to patients, physicians, and healthcare systems. We developed a quality of care score based on the Atrial Fibrillation Better Care pathway recommended by the European Society of Cardiology and the European Heart Rhythm Association guidelines. This is a 14-point score that we have termed the MAGIC score(Management of Atrial Fibrillation in Integrated Care and General Practice). OBJECTIVE: The objective of this pilot study was to develop and test a quality of care score for patients with permanent AF in general practice. METHODS: An observational cross-sectional pilot study was undertaken. Proportionate sampling was used across 11 practices from the Ireland East practice-based research network. The GPs completed a report form on each patient by undertaking a retrospective chart review. Eleven practices participated with a total of 1855 patients with AF. We received data on 153 patients. RESULTS: The main findings were that no patient met all 14 guideline based recommendations. The mean MAGIC score was 11.3. Points were most commonly deducted because the creatinine clearance and HAS-BLED score were not recorded, and the patient was not on the correct dose of oral anti-coagulation. CONCLUSION: This study demonstrates the feasibility of using a quality of care score to measure the quality of AF management in general practice. This scoring system, which is based on internationally recognized quality of care markers, highlights key areas that can be targeted with quality improvement intervention.

Atrial fibrillation (AF) is the most common arrhythmia in the world. An arrhythmia is when your heart beats in a disorganized way with no pattern. AF is a serious health problem because this rhythm can lead to other heart problems, stroke, and even death. Even though it is common, we know that people with AF do not always receive the correct treatment and monitoring. Treatment aims to control the heart rate, rhythm and minimize blood clot formation. Treating patients according to recommended guidelines will improve their medical care and outcomes. We created a 14-point quality-of-care score based on international clinical practice guidelines. This project was done to check if this score was practical to use and if it showed any patterns in the quality of care being delivered. Eleven GP practices from the Southeast of Ireland participated and gave us information on 153 patients with AF. We assigned each chart a quality-of-care score based on the tool we developed. No chart scored 14 points (full marks). The most common reasons for points being deducted were not recording kidney function, bleeding risk, and the patients being on the wrong dose of medication. With this information, we can now move forward and try to improve care for these patients by targeting the highlighted deficits.

Continuous Positive Airway Pressure but Not GLP1-mediated Weight Loss Improves Early Cardiovascular Disease in Obstructive Sleep Apnea: A Randomized Proof-of-Concept Study.

Rationale: Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular (CV) morbidity and mortality, but the benefit of continuous positive airway pressure (CPAP) is uncertain. However, most randomized controlled trials have focused on the role of CPAP in secondary prevention, although there is growing evidence of a potential benefit on early CV disease. Weight loss in combination with CPAP may be superior but is difficult to achieve and maintain with conventional measures alone. Objectives: The aim of this study was to gain insights into the effect of CPAP on early atherosclerotic processes and to compare it with a glucagon-like peptide (GLP)-1-mediated weight loss regimen in patients with OSA. Methods: We performed a randomized proof-of-concept study comparing CPAP, a GLP1-mediated weight-loss regimen (liraglutide [Lir]), and both in combination for 24 weeks in 30 consecutive patients with OSA (apnea-hypopnea index >15 events/h; body mass index 30-40 kg/m2; and no history of diabetes, heart failure, or unstable CV disease). In addition to extensive evaluation for CV risk factors and endothelial function at baseline and end of study, subjects underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18F-FDG PET-CT) for the measurement of aortic wall inflammation (target-to-background ratio) and coronary computed tomography angiography for semiautomated coronary plaque analysis. Results: Baseline characteristics were similar between groups. CPAP alone and in combination resulted in greater reduction in apnea-hypopnea index than Lir alone (mean difference, -45 and -43 events/h, respectively, vs. -12 events/h; P < 0.05). Both Lir and combination treatment led to significant weight loss, but only CPAP alone resulted in significant decrease in vascular inflammation (aortic wall target-to-background ratio from 2.03 ± 0.34 to 1.84 ± 0.43; P = 0.010), associated with an improvement in endothelial function and a decrease in C-reactive protein. Low-attenuation coronary artery plaque volume as a marker of unstable plaque also decreased with CPAP (from 571 ± 490 to 334 ± 185 mm3) and with combination therapy (from 401 ± 145 to 278 ± 126 mm3) but not with Lir. Conclusions: These data suggest that CPAP therapy, but not GLP1-mediated weight loss, improves vascular inflammation and reduces unstable plaque volume in patients with OSA. Further large randomized controlled studies are warranted to assess the benefit of CPAP therapy in modifying early CV disease. Clinical trial registered with www.clinicaltrials.gov (NCT04186494).

Management of iron deficiency in women of childbearing age with oral iron intolerance: a prospective, randomised, controlled trial of three doses of an iron-whey-protein formulation : Prospective RandomisEd study of women of Childbearing age with gastroInteStinal Intolerance to Oral iroN (PRECISION).

BACKGROUND: Nutritional deficit and oral iron gastrointestinal intolerance may be a common cause of iron deficiency, which can be managed by pharmacists. AIM: To understand the prevalence of iron deficiency in women of childbearing age with a self-reported history of intolerance to oral iron and the tolerability of three doses of an iron-whey-protein formulation in the care of these women. METHOD: Ferritin and haemoglobin levels were documented in women of childbearing age with oral iron gastrointestinal intolerance. In those with iron deficiency (ferritin < 30 µg/L), adherence, gastrointestinal tolerability, ferritin, transferrin saturation and haemoglobin levels were compared between their prior oral iron product and iron-whey-protein microspheres randomised to three doses (14 mg daily, 25 mg daily and 50 mg daily) for 12 weeks. RESULTS: Most screened women had low iron stores (128 (62.7%); ferritin < 30 µg/L), 65 (31.9%) had moderate to severe iron deficiency (ferritin < 12 µg/L) and 33 (16.2%) had iron deficiency anaemia (ferritin < 30 µg/L, haemoglobin < 12 g/dL). Amongst the 59 women who participated in the prospective clinical study of iron-whey-protein microspheres over 12 weeks, 48 (81.4%) were classified as adherent/persistent and fewer instances of gastrointestinal intolerance were reported (0.59 ± 0.91) when compared to 12 (20.3%) and (4.0 ± 2.2) respectively while taking the prior oral iron (Fisher's Exact and T-test respectively, both p < 0.001). There was no difference in adherence or tolerability of different iron-whey-protein formulation doses. Ferritin, haemoglobin and energy levels increased significantly over 12 weeks. CONCLUSION: Undiagnosed iron deficiency is common in women of childbearing age with a history of intolerance to oral iron and iron-whey-protein microspheres can improve adherence, GI tolerability, iron stores, haemoglobin and energy levels in these women. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier (registration includes full trial protocol): NCT04778072.

Non-specific effects of Pneumococcal and Haemophilus vaccines in children aged 5 years and under: a systematic review.

OBJECTIVE: To determine the evidence for non-specific effects of the Pneumococcal and Haemophilus influenza vaccine in children aged 5 years and under. DATA SOURCES: A key word literature search of MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, the European Union Clinical Trials Register and ClinicalTrials.gov up to June 2023. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs), quasi-RCT or cohort studies. PARTICIPANTS: Children aged 5 or under. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies were independently screened by two reviewers, with a third where disagreement arose. Risk of bias assessment was performed by one reviewer and confirmed by a second. Results were tabulated and a narrative description performed. RESULTS: Four articles were identified and included in this review. We found a reduction in hospitalisations from influenza A (44%), pulmonary tuberculosis (42%), metapneumovirus (45%), parainfluenza virus type 1-3 (44%), along with reductions in mortality associated with pneumococcal vaccine. No data on the Haemophilus vaccine was found. CONCLUSIONS AND IMPLICATIONS: In this systematic review, we demonstrate that there is a reduction in particular viral infections in children aged 5 years and under who received the 9-valent pneumococcal conjugate vaccine which differ from those for which the vaccine was designed to protect against. While limited studies have demonstrated a reduction in infections other than those which the vaccine was designed to protect against, substantial clinical trials are required to solidify these findings. PROSPERO REGISTRATION NUMBER: CRD42020146640.

Heart failure virtual consultation: caters for frailer, multimorbid and remote patients.

BACKGROUND: The heart failure (HF) virtual consultation (VC) is an eHealth tool for delivery of peer-to-peer specialist advice to general practitioners (GPs) to discuss HF diagnosis/management. We aim to investigate the impact of the VC service on onward referral rate and quality of assessment by GPs, as well as assess VC patient characteristics; Clinical Frailty Score (CSF), age and morbidity. METHODS: This prospective observational study collected VC data on: demographics, comorbidity, frailty, referral indication, the impact of VC on clinical care and the GP response to the question 'what would you have done without the VC service'. We compared patient characteristics to a control population of patients attending the HF unit (HFU) (n=118). REULTS: Between 2015 and 2021, 1681 VC cases were discussed. The majority of cases were discussed from remote areas (75%). Rediscussion cases increased from 0% to 34%. VC patients were older (76.2 (±11.3) vs 73.1 (±12.5) years, p<0.05), more frail (CSF=3.8 (±1.7) vs 3 (±1.6), p<0.01) and multimorbid (number of comorbidities=7.1 (±3.4) vs 3.8 (±1.9), p<0.001) compared with patients attending the HFU. Without the VC, 93% of cases would have been referred to face-to-face hospital services. Instead, VC resulted in only 9% of cases being referred to hospital services. The remainder of cases were managed by the VC service, in a shared GP-specialist approach. GP use of natriuretic peptide (NP) increased from 0% in 2015-2016 to 63% in 2021 and use of TTE increased from 0% in 2015-2016 to 69% by 2021. CONCLUSIONS: The VC service provides a platform for case discussion in particular for older, frailer patients and reduces onward hospital referrals. This may facilitate early diagnosis and management of suspected HF in the current era of long outpatient waiting times. The quality of community HF assessment improved as indicated by increased use of NP/TTE by GPs.

Effect of Sacubitril/Valsartan vs Valsartan on Left Atrial Volume in Patients With Pre-Heart Failure With Preserved Ejection Fraction: The PARABLE Randomized Clinical Trial.

Importance: Pre-heart failure with preserved ejection fraction (pre-HFpEF) is common and has no specific therapy aside from cardiovascular risk factor management. Objective: To investigate the hypothesis that sacubitril/valsartan vs valsartan would reduce left atrial volume index using volumetric cardiac magnetic resonance imaging in patients with pre-HFpEF. Design, Setting, and Participants: The Personalized Prospective Comparison of ARNI [angiotensin receptor/neprilysin inhibitor] With ARB [angiotensin-receptor blocker] in Patients With Natriuretic Peptide Elevation (PARABLE) trial was a prospective, double-blind, double-dummy, randomized clinical trial carried out over 18 months between April 2015 and June 2021. The study was conducted at a single outpatient cardiology center in Dublin, Ireland. Of 1460 patients in the STOP-HF program or outpatient cardiology clinics, 461 met initial criteria and were approached for inclusion. Of these, 323 were screened and 250 asymptomatic patients 40 years and older with hypertension or diabetes, elevated B-type natriuretic peptide (BNP) greater than 20 pg/mL or N-terminal pro-b-type natriuretic peptide greater than 100 pg/mL, left atrial volume index greater than 28 mL/m2, and preserved ejection fraction greater than 50% were included. Interventions: Patients were randomized to angiotensin receptor neprilysin inhibitor sacubitril/valsartan titrated to 200 mg twice daily or matching angiotensin receptor blocker valsartan titrated to 160 mg twice daily. Main Outcomes and Measures: Maximal left atrial volume index and left ventricular end diastolic volume index, ambulatory pulse pressure, N-terminal pro-BNP, and adverse cardiovascular events. Results: Among the 250 participants in this study, the median (IQR) age was 72.0 (68.0-77.0) years; 154 participants (61.6%) were men and 96 (38.4%) were women. Most (n = 245 [98.0%]) had hypertension and 60 (24.0%) had type 2 diabetes. Maximal left atrial volume index was increased in patients assigned to receive sacubitril/valsartan (6.9 mL/m2; 95% CI, 0.0 to 13.7) vs valsartan (0.7 mL/m2; 95% CI, -6.3 to 7.7; P < .001) despite reduced markers of filling pressure in both groups. Changes in pulse pressure and N-terminal pro-BNP were lower in the sacubitril/valsartan group (-4.2 mm Hg; 95% CI, -7.2 to -1.21 and -17.7%; 95% CI, -36.9 to 7.4, respectively; P < .001) than the valsartan group (-1.2 mm Hg; 95% CI, -4.1 to 1.7 and 9.4%; 95% CI, -15.6 to 4.9, respectively; P < .001). Major adverse cardiovascular events occurred in 6 patients (4.9%) assigned to sacubitril/valsartan and 17 (13.3%) assigned to receive valsartan (adjusted hazard ratio, 0.38; 95% CI, 0.17 to 0.89; adjusted P = .04). Conclusions and Relevance: In this trial of patients with pre-HFpEF, sacubitril/valsartan treatment was associated with a greater increase in left atrial volume index and improved markers of cardiovascular risk compared to valsartan. More work is needed to understand the observed increased cardiac volumes and long-term effects of sacubitril/valsartan in patients with pre-HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT04687111.

FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility.

Heart failure (HF) is the leading cause of hospitalisations worldwide, with only 35% of patients surviving the first 5 years after diagnosis. The pathogenesis of HF with preserved ejection fraction (HFpEF) is still unclear, impeding the implementation of effective treatments. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are critical mediators of angiogenesis and inflammation. Thus, in this study, we investigated-for the first time-FKBPL's role in the pathogenesis and as a biomarker of HFpEF. In vitro models of cardiac hypertrophy following exposure to a hypertensive stimulus, angiotensin-II (Ang-II, 100 nM), and/or AD-01 (100 nM), for 24 and 48 h were employed as well as human plasma samples from people with different forms of HFpEF and controls. Whilst the FKBPL peptide mimetic, AD-01, induced cardiomyocyte hypertrophy in a similar manner to Ang-II (p < 0.0001), when AD-01 and Ang-II were combined together, this process was abrogated (p < 0.01-0.0001). This mechanism appears to involve a negative feedback loop related to FKBPL (p < 0.05). In human plasma samples, FKBPL concentration was increased in HFpEF compared to controls (p < 0.01); however, similar to NT-proBNP and Gal-3, it was unable to stratify between different forms of HFpEF: acute HFpEF, chronic HFpEF and hypertrophic cardiomyopathy (HCM). FKBPL may be explored for its biomarker and therapeutic target potential in HFpEF.

Sustainable protocol-based management of hypertension in one institution in northern Malawi.

INTRODUCTION: Across all WHO regions, Africa has the highest prevalence of hypertension with 46% of the population >25 years estimated to be hypertensive. Blood pressure (BP) control is poor, with <40% of hypertensives diagnosed, <30% of those diagnosed receiving medical treatment, and <20% with adequate control. We report an intervention to improve BP control in a cohort of hypertensive patients attending a single hospital in Mzuzu Malawi, by introducing a limited protocol of four antihypertensive medications taken once-daily. METHODS: A drug protocol based on international guidelines, drug availability in Malawi, cost and clinical effectiveness was developed and implemented. Patients were transitioned to the new protocol as they attended for clinic visits. Records of 109 patients completing at least three visits were assessed for BP control. RESULTS: Two-thirds of patients (n=73) were female and average age at enrolment was 61.6 ± 12.8 years. Median [interquartile range] systolic BP (SBP) was 152 [136;167] mm Hg at baseline and reduced over the follow-up period to 148 [135; 157, p<0.001 vs baseline]. Median diastolic BP (DBP) reduced from 90.0 [82.0; 100] mm Hg to 83.0 [77.0; 91.0], p<0.001 vs baseline. Patients with highest baseline blood pressures benefited most and there were no associations noted between BP responses and either age or gender. DISCUSSION: We conclude that a limited evidence based once-daily drug regimen can improve blood pressure control by comparison with standard management. Cost effectiveness of this approach will also be reported.

Public perceptions of pharmacogenomic services in Ireland - Are people with chronic disease more likely to want service availability than those without? A questionnaire study.

Background: As pharmacogenomic services begin to emerge in primary care, the insight of the public is crucial for its integration into clinical practice. Objectives: To establish perceptions of pharmacogenomics (awareness, understanding, openness to availability, perceived benefits and concerns, willingness to pay, and service setting) and investigate if they differ between those with and without chronic disease(s). Methods: An anonymous, online questionnaire generated using Qualtrics® and circulated via social media and posters placed in eight participating community pharmacies was conducted with Irish adults. The questions were designed to consider existing literature on patient perceptions of pharmacogenomics. Descriptive statistics were used to summarize questionnaire responses. Chi-square test was used to compare categorical variables, while independent sample t-test and one-way ANOVA were used to compare the mean values of two (with and without chronic disease) and three groups (multimorbidity (two or more chronic conditions) and polypharmacy (prescribed four or more regular medicines) (MMPP), a single chronic disease, and those without existing medical conditions) respectively Logistic regression was used to evaluate age and gender adjusted associations of chronic disease(s) with responses. A p-value <0.05 was considered statistically significant. Results: A total of 421 responses were received, 30% (n = 120) of whom reported having a chronic disease. Overall, respondents reported low awareness (44%, n = 166) and poor knowledge (55%, n = 212) of pharmacogenomics. After explaining pharmacogenomics to respondents, patients with chronic disease(s) were 2.17 times more likely (p < 0.001) to want pharmacogenomic services availability than those without existing conditions, adjusted for age and gender (driven by preferences of those with MMPP than those with single chronic disease). Respondents demonstrated a high level of interest and noted both the potential benefits and downsides of pharmacogenomic testing. Willingness-to-pay was not associated with having a chronic disease and respondents were more positive about primary care (community pharmacy or general practice) rather than hospital-based pharmacogenomics implementation. Conclusion: The Irish public in general and those with chronic disease in particular are strongly supportive of pharmacogenomic testing, highlighting an unmet need for its incorporation in medicines optimization. These data underline the need for more research on the implementation of community-based pharmacogenomics services for MMPP patients and ubiquitous pharmacogenomics education programs.

Cardiac MRI e-prime predicts myocardial late gadolinium enhancement and diastolic dysfunction in hypertrophic cardiomyopathy.

BACKGROUND: Myocardial fibrosis leads to diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). OBJECTIVES: To evaluate a manual method of measuring mitral annular relaxation velocity (termed cardiac MRI e') as a measure of diastolic dysfunction on routine cardiac MRI and its relationship with myocardial late-gadolinium enhancement (LGE) and feature tracking measures of diastolic dysfunction in patients with HCM. METHODS: CMR e', feature tracking measures of diastolic function, left atrial, left ventricular (LV) parameters and LGE were retrospectively measured in 75 patients with HCM (mean age, 54.7 years ± 15.3, 54 men). Multivariate regression and partial Spearman correlations were performed. RESULTS: Cardiac MRI e' measures correlated with LGE (r = 0.49, P < 0.001) and multiple feature tracking measures of diastolic function, adjusted for patient demographics, left atrial and left ventricular parameters. Cardiac MRI e' measures were independently predictive of LGE ≥ 10% (mean total cardiac MRI e': LGE < 10% vs LGE ≥ 10% was 3.5 cm/s vs. 1.7 cm/s, P < 0.001). Superior CMR e' had an AUC of 0.79 [95%CI 0.66-0.92, P < 0.0001]) in predicting patients with LGE ≥ 10% and a cutoff of 1.7 cm/s resulted in a sensitivity and specificity of 81.0% and 78.0% respectively. CONCLUSION: Cardiac MRI e' is a manual measure of LV diastolic dysfunction acquired on routine cardiac MRI without specialized software and is an independent predictor of LGE ≥ 10% and diastolic dysfunction in HCM.

Pharmacogenetic interventions to improve outcomes in patients with multimorbidity or prescribed polypharmacy: a systematic review.

Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to healthcare delivery is required. Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was undertaken to summarise the data; meta-analysis was inappropriate due to study heterogeneity. Fifteen studies of diverse design and variable quality were included. A small, randomised study involving pharmacist-led medicines optimisation, including pharmacogenetics, suggests this approach could have significant benefits for patients and health systems. However, due to study design heterogeneity and the quality of the included studies, it is difficult to draw generalisable conclusions. Further pragmatic, robust pharmacogenetics studies in diverse, real-world patient populations, are required to establish the benefit of multi-medicine pharmacogenetic screening on patient outcomes.

Heart Failure diagnosis based on deep learning techniques.

The aim of the study is to address the heart failure (HF) diagnosis with the application of deep learning approaches. Seven deep learning architectures are implemented, where stacked Restricted Boltzman Machines (RBMs) and stacked Autoencoders (AEs) are used to pre-train Deep Belief Networks (DBN) and Deep Neural Networks (DNN). The data is provided by the University College Dublin and the 2nd Department of Cardiology from the University Hospital of Ioannina. The features recorded are grouped into: general demographic information, physical examination, classical cardiovascular risk factors, personal history of cardiovascular disease, symptoms, medications, echocardiographic features, laboratory findings, lifestyle/habits and other diseases. The total number of subjects utilized is 422. The deep learning methods provide quite high results with the Autoencoder plus DNN approach to demonstrate accuracy 91.71%, sensitivity 90.74%, specificity 92.31% and f-score 89.36%.

A Machine Learning Approach for Chronic Heart Failure Diagnosis.

The aim of this study was to address chronic heart failure (HF) diagnosis with the application of machine learning (ML) approaches. In the present study, we simulated the procedure that is followed in clinical practice, as the models we built are based on various combinations of feature categories, e.g., clinical features, echocardiogram, and laboratory findings. We also investigated the incremental value of each feature type. The total number of subjects utilized was 422. An ML approach is proposed, comprising of feature selection, handling class imbalance, and classification steps. The results for HF diagnosis were quite satisfactory with a high accuracy (91.23%), sensitivity (93.83%), and specificity (89.62%) when features from all categories were utilized. The results remained quite high, even in cases where single feature types were employed.

A Systematic Review of Clinical Prediction Rules to Predict Hospitalisation in Children with Lower Respiratory Infection in Primary Care and their Validation in a New Cohort.

Background: Our goal was to identify existing clinical prediction rules for predicting hospitalisation due to lower respiratory tract infection (LRTI) in children in primary care, guiding antibiotic therapy. A validation of these rules was then performed in a novel cohort of children presenting to primary care in Malawi with World Health Organisation clinically defined pneumonia. Methods: MEDLINE & EMBASE databases were searched for studies on the development, validation and clinical impact of clinical prediction models for hospitalisation in children with lower respiratory tract infection between January 1st1946-June 30th 2021. Two reviewers screened all abstracts and titles independently. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews & Meta-Analyses guidelines. The BIOTOPE cohort (BIOmarkers TO diagnose PnEumonia) recruited children aged 2-59 months with WHO-defined pneumonia from two primary care facilities in Mzuzu, Malawi. Validation of identified rules was undertaken in this cohort. Findings: 1023 abstracts were identified. Following the removal of duplicates, a review of 989 abstracts was conducted leading to the identification of one eligible model. The CHARMS checklist for prediction modelling studies was utilized for evaluation. The area under the curve (AUC) of the STARWAVe rule for hospitalisation in BIOTOPE was found to be 0.80 (95% C.I of 0.75-0.85). The AUC of STARWAVe for a confirmed diagnosis of bacterial pneumonia was 0.39 (95% C.I 0.25-0.54). Interpretation: This review highlights the lack of clinical prediction rules in this area. The STARWAVe rule identified was useful in predicting hospitalisation from bacterial infection as defined. However, in the absence of a gold standard indicator for bacterial LRTI, this is a reasonable surrogate and could lead to reductions in antibiotic prescription rates, should clinical impact studies prove its utility. Further work to determine the clinical impact of STARWAVe and to identify diagnostic tests for bacterial LRTI in primary care is required.

NT-proBNP/BNP ratio for prognostication in European Caucasian patients enrolled in a heart failure prevention programme.

AIMS: Guidelines support the role of B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) for risk stratification of patients in programmes to prevent heart failure (HF). Although biologically formed in a 1:1 ratio, the ratio of NT-proBNP to BNP exhibits wide inter-individual variability. A report on an Asian population suggests that molar NT-proBNP/BNP ratio is associated with incident HF. This study aims to determine whether routine, simultaneous evaluation of both BNP and NT-proBNP is warranted in a European, Caucasian population. METHODS AND RESULTS: We determined BNP and NT-proBNP levels for 782 Stage A/B HF patients in the STOP-HF programme. The clinical, echocardiographic, and biochemical associates of molar NT-proBNP/BNP ratio were analysed. The primary endpoint was the adjusted association of baseline molar NT-proBNP/BNP ratio with new-onset HF and/or progression of left ventricular dysfunction (LVD). We estimated the C-statistic, integrated discrimination improvement, and the category-free net reclassification improvement metric for the addition of molar NT-proBNP/BNP ratio to adjusted models. The median age was 66.6 years [interquartile range (IQR) 59.5-73.1], 371 (47.4%) were female, and median molar NT-proBNP/BNP ratio was 1.91 (IQR 1.37-2.93). Estimated glomerular filtration rate, systolic blood pressure, left ventricular mass index, and heart rate were associated with NT-proBNP/BNP ratio in a linear regression model (all P < 0.05). Over a median follow-up period of 5 years (IQR 3.4-6.8), 247 (31.5%) patients developed HF or progression of LVD. Log-transformed NT-proBNP/BNP ratio is inversely associated with HF and LVD risk when adjusted for age, gender, diabetes, hypertension, vascular disease, obesity, heart rate, number of years of follow-up, estimated glomerular filtration rate, and baseline NT-proBNP (odds ratio 0.71, 95% confidence interval 0.55-0.91; P = 0.008). However, molar NT-proBNP/BNP ratio did not increase the C-statistic (Δ -0.01) and net reclassification improvement (0.0035) for prediction of HF and LVD compared with NT-proBNP or BNP alone. Substitution of NT-proBNP for BNP in the multivariable model eliminated the association with HF and LVD risk. CONCLUSIONS: This study characterized, for the first time in a Caucasian Stage A/B HF population, the relationship between NT-proBNP/BNP ratio and biological factors and demonstrated an inverse relationship with the future development of HF and LVD. However, this study does not support routine simultaneous BNP and NT-proBNP measurement in HF prevention programmes amongst European, Caucasian patients.

STOP-HF Trial: Higher Endogenous BNP and Cardiovascular Protection in Subjects at Risk for Heart Failure.

B-type natriuretic peptide (BNP) possesses blood-pressure-lowering, antifibrotic, and aldosterone-suppressing properties. In Stage A and B heart failure, the carriers of the minor C allele of the BNP genetic variant rs198389 have higher circulating levels of BNP and are at decreased risk of hypertension, new-onset left ventricular systolic dysfunction, and hospitalization for major adverse cardiovascular events. Future studies are warranted to investigate the role of BNP genetic testing and BNP-based therapy in the prevention of heart failure.