Artificial intelligence to enhance clinical value across the spectrum of cardiovascular healthcare.

Artificial intelligence (AI) is increasingly being utilized in healthcare. This article provides clinicians and researchers with a step-wise foundation for high-value AI that can be applied to a variety of different data modalities. The aim is to improve the transparency and application of AI methods, with the potential to benefit patients in routine cardiovascular care. Following a clear research hypothesis, an AI-based workflow begins with data selection and pre-processing prior to analysis, with the type of data (structured, semi-structured, or unstructured) determining what type of pre-processing steps and machine-learning algorithms are required. Algorithmic and data validation should be performed to ensure the robustness of the chosen methodology, followed by an objective evaluation of performance. Seven case studies are provided to highlight the wide variety of data modalities and clinical questions that can benefit from modern AI techniques, with a focus on applying them to cardiovascular disease management. Despite the growing use of AI, further education for healthcare workers, researchers, and the public are needed to aid understanding of how AI works and to close the existing gap in knowledge. In addition, issues regarding data access, sharing, and security must be addressed to ensure full engagement by patients and the public. The application of AI within healthcare provides an opportunity for clinicians to deliver a more personalized approach to medical care by accounting for confounders, interactions, and the rising prevalence of multi-morbidity.

Redefining ß-blocker response in heart failure patients with sinus rhythm and atrial fibrillation: a machine learning cluster analysis.

BACKGROUND: Mortality remains unacceptably high in patients with heart failure and reduced left ventricular ejection fraction (LVEF) despite advances in therapeutics. We hypothesised that a novel artificial intelligence approach could better assess multiple and higher-dimension interactions of comorbidities, and define clusters of ß-blocker efficacy in patients with sinus rhythm and atrial fibrillation. METHODS: Neural network-based variational autoencoders and hierarchical clustering were applied to pooled individual patient data from nine double-blind, randomised, placebo-controlled trials of ß blockers. All-cause mortality during median 1·3 years of follow-up was assessed by intention to treat, stratified by electrocardiographic heart rhythm. The number of clusters and dimensions was determined objectively, with results validated using a leave-one-trial-out approach. This study was prospectively registered with ClinicalTrials.gov (NCT00832442) and the PROSPERO database of systematic reviews (CRD42014010012). FINDINGS: 15 659 patients with heart failure and LVEF of less than 50% were included, with median age 65 years (IQR 56-72) and LVEF 27% (IQR 21-33). 3708 (24%) patients were women. In sinus rhythm (n=12 822), most clusters demonstrated a consistent overall mortality benefit from ß blockers, with odds ratios (ORs) ranging from 0·54 to 0·74. One cluster in sinus rhythm of older patients with less severe symptoms showed no significant efficacy (OR 0·86, 95% CI 0·67-1·10; p=0·22). In atrial fibrillation (n=2837), four of five clusters were consistent with the overall neutral effect of ß blockers versus placebo (OR 0·92, 0·77-1·10; p=0·37). One cluster of younger atrial fibrillation patients at lower mortality risk but similar LVEF to average had a statistically significant reduction in mortality with ß blockers (OR 0·57, 0·35-0·93; p=0·023). The robustness and consistency of clustering was confirmed for all models (p<0·0001 vs random), and cluster membership was externally validated across the nine independent trials. INTERPRETATION: An artificial intelligence-based clustering approach was able to distinguish prognostic response from ß blockers in patients with heart failure and reduced LVEF. This included patients in sinus rhythm with suboptimal efficacy, as well as a cluster of patients with atrial fibrillation where ß blockers did reduce mortality. FUNDING: Medical Research Council, UK, and EU/EFPIA Innovative Medicines Initiative BigData@Heart.

Identification and Mapping Real-World Data Sources for Heart Failure, Acute Coronary Syndrome, and Atrial Fibrillation.

BACKGROUND: Transparent and robust real-world evidence sources are increasingly important for global health, including cardiovascular (CV) diseases. We aimed to identify global real-world data (RWD) sources for heart failure (HF), acute coronary syndrome (ACS), and atrial fibrillation (AF). METHODS: We conducted a systematic review of publications with RWD pertaining to HF, ACS, and AF (2010-2018), generating a list of unique data sources. Metadata were extracted based on the source type (e.g., electronic health records, genomics, and clinical data), study design, population size, clinical characteristics, follow-up duration, outcomes, and assessment of data availability for future studies and linkage. RESULTS: Overall, 11,889 publications were retrieved for HF, 10,729 for ACS, and 6,262 for AF. From these, 322 (HF), 287 (ACS), and 220 (AF) data sources were selected for detailed review. The majority of data sources had near complete data on demographic variables (HF: 94%, ACS: 99%, and AF: 100%) and considerable data on comorbidities (HF: 77%, ACS: 93%, and AF: 97%). The least reported data categories were drug codes (HF, ACS, and AF: 10%) and caregiver involvement (HF: 6%, ACS: 1%, and AF: 1%). Only a minority of data sources provided information on access to data for other researchers (11%) or whether data could be linked to other data sources to maximize clinical impact (20%). The list and metadata for the RWD sources are publicly available at www.escardio.org/bigdata. CONCLUSIONS: This review has created a comprehensive resource of CV data sources, providing new avenues to improve future real-world research and to achieve better patient outcomes.

Machine learning for subtype definition and risk prediction in heart failure, acute coronary syndromes and atrial fibrillation: systematic review of validity and clinical utility.

BACKGROUND: Machine learning (ML) is increasingly used in research for subtype definition and risk prediction, particularly in cardiovascular diseases. No existing ML models are routinely used for cardiovascular disease management, and their phase of clinical utility is unknown, partly due to a lack of clear criteria. We evaluated ML for subtype definition and risk prediction in heart failure (HF), acute coronary syndromes (ACS) and atrial fibrillation (AF). METHODS: For ML studies of subtype definition and risk prediction, we conducted a systematic review in HF, ACS and AF, using PubMed, MEDLINE and Web of Science from January 2000 until December 2019. By adapting published criteria for diagnostic and prognostic studies, we developed a seven-domain, ML-specific checklist. RESULTS: Of 5918 studies identified, 97 were included. Across studies for subtype definition (n = 40) and risk prediction (n = 57), there was variation in data source, population size (median 606 and median 6769), clinical setting (outpatient, inpatient, different departments), number of covariates (median 19 and median 48) and ML methods. All studies were single disease, most were North American (n = 61/97) and only 14 studies combined definition and risk prediction. Subtype definition and risk prediction studies respectively had limitations in development (e.g. 15.0% and 78.9% of studies related to patient benefit; 15.0% and 15.8% had low patient selection bias), validation (12.5% and 5.3% externally validated) and impact (32.5% and 91.2% improved outcome prediction; no effectiveness or cost-effectiveness evaluations). CONCLUSIONS: Studies of ML in HF, ACS and AF are limited by number and type of included covariates, ML methods, population size, country, clinical setting and focus on single diseases, not overlap or multimorbidity. Clinical utility and implementation rely on improvements in development, validation and impact, facilitated by simple checklists. We provide clear steps prior to safe implementation of machine learning in clinical practice for cardiovascular diseases and other disease areas.

Effect of Digoxin vs Bisoprolol for Heart Rate Control in Atrial Fibrillation on Patient-Reported Quality of Life: The RATE-AF Randomized Clinical Trial.

Importance: There is little evidence to support selection of heart rate control therapy in patients with permanent atrial fibrillation, in particular those with coexisting heart failure. Objective: To compare low-dose digoxin with bisoprolol (a ß-blocker). Design, Setting, and Participants: Randomized, open-label, blinded end-point clinical trial including 160 patients aged 60 years or older with permanent atrial fibrillation (defined as no plan to restore sinus rhythm) and dyspnea classified as New York Heart Association class II or higher. Patients were recruited from 3 hospitals and primary care practices in England from 2016 through 2018; last follow-up occurred in October 2019. Interventions: Digoxin (n = 80; dose range, 62.5-250 µg/d; mean dose, 161 µg/d) or bisoprolol (n = 80; dose range, 1.25-15 mg/d; mean dose, 3.2 mg/d). Main Outcomes and Measures: The primary end point was patient-reported quality of life using the 36-Item Short Form Health Survey physical component summary score (SF-36 PCS) at 6 months (higher scores are better; range, 0-100), with a minimal clinically important difference of 0.5 SD. There were 17 secondary end points (including resting heart rate, modified European Heart Rhythm Association [EHRA] symptom classification, and N-terminal pro-brain natriuretic peptide [NT-proBNP] level) at 6 months, 20 end points at 12 months, and adverse event (AE) reporting. Results: Among 160 patients (mean age, 76 [SD, 8] years; 74 [46%] women; mean baseline heart rate, 100/min [SD, 18/min]), 145 (91%) completed the trial and 150 (94%) were included in the analysis for the primary outcome. There was no significant difference in the primary outcome of normalized SF-36 PCS at 6 months (mean, 31.9 [SD, 11.7] for digoxin vs 29.7 [11.4] for bisoprolol; adjusted mean difference, 1.4 [95% CI, -1.1 to 3.8]; P = .28). Of the 17 secondary outcomes at 6 months, there were no significant between-group differences for 16 outcomes, including resting heart rate (a mean of 76.9/min [SD, 12.1/min] with digoxin vs a mean of 74.8/min [SD, 11.6/min] with bisoprolol; difference, 1.5/min [95% CI, -2.0 to 5.1/min]; P = .40). The modified EHRA class was significantly different between groups at 6 months; 53% of patients in the digoxin group reported a 2-class improvement vs 9% of patients in the bisoprolol group (adjusted odds ratio, 10.3 [95% CI, 4.0 to 26.6]; P < .001). At 12 months, 8 of 20 outcomes were significantly different (all favoring digoxin), with a median NT-proBNP level of 960 pg/mL (interquartile range, 626 to 1531 pg/mL) in the digoxin group vs 1250 pg/mL (interquartile range, 847 to 1890 pg/mL) in the bisoprolol group (ratio of geometric means, 0.77 [95% CI, 0.64 to 0.92]; P = .005). Adverse events were less common with digoxin; 20 patients (25%) in the digoxin group had at least 1 AE vs 51 patients (64%) in the bisoprolol group (P < .001). There were 29 treatment-related AEs and 16 serious AEs in the digoxin group vs 142 and 37, respectively, in the bisoprolol group. Conclusions and Relevance: Among patients with permanent atrial fibrillation and symptoms of heart failure treated with low-dose digoxin or bisoprolol, there was no statistically significant difference in quality of life at 6 months. These findings support potentially basing decisions about treatment on other end points. Trial Registration: ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.

Binaural hearing is impaired in children with hearing loss who use bilateral hearing aids.

This paper asked whether children fitted with bilateral hearing aids (BHA) develop normal perception of binaural cues which are the basis of spatial hearing. Data from children with BHA (n = 26, age = 12.6 ± 2.84 years) were compared to data from a control group (n = 12, age = 12.36 ± 2.83 years). Stimuli were 250 Hz click-trains of 36 ms and a 40 ms consonant-vowel /da/ at 1 Hz presented through ER3A insert-earphones unilaterally or bilaterally. Bilateral stimuli were presented at different interaural level difference (ILD) and interaural timing difference (ITD) conditions. Participants indicated whether the sound came from the left or right side (lateralization) or whether one sound or two could be heard (binaural fusion). BHA children lateralized ILDs similarly to the control group but had impaired lateralization of ITDs. Longer response times relative to controls suggest that lateralization of ITDs was challenging for children with BHA. Most, but not all, of the BHA group were able to fuse click and speech sounds similarly to controls. Those unable to fuse showed particularly poor ITD lateralization. Results suggest that ITD perception is abnormal in children using BHAs, suggesting persistent effects of hearing loss that are not remediated by present clinical rehabilitation protocols.

Remote monitoring of atrial fibrillation recurrence using mHealth technology (REMOTE-AF).

Aims: This proof-of-concept study sought to evaluate changes in heart rate (HR) obtained from a consumer wearable device and compare against implantable loop recorder (ILR)-detected recurrence of atrial fibrillation (AF) and atrial tachycardia (AT) after AF ablation. Methods and results: REMOTE-AF (NCT05037136) was a prospectively designed sub-study of the CASA-AF randomized controlled trial (NCT04280042). Participants without a permanent pacemaker had an ILR implanted at their index ablation procedure for longstanding persistent AF. Heart rate and step count were continuously monitored using photoplethysmography (PPG) from a commercially available wrist-worn wearable. Photoplethysmography-recorded HR data were pre-processed with noise filtration and episodes at 1-min interval over 30 min of HR elevations (Z-score = 2) were compared with corresponding ILR data. Thirty-five patients were enrolled, with mean age 70.3 ± 6.8 years and median follow-up 10 months (interquartile range 8-12 months). Implantable loop recorder analysis revealed 17 out of 35 patients (49%) had recurrence of AF/AT. Compared with ILR recurrence, wearable-derived elevations in HR ≥ 110 beats per minute had a sensitivity of 95.3%, specificity 54.1%, positive predictive value (PPV) 15.8%, negative predictive value (NPV) 99.2%, and overall accuracy 57.4%. With PPG-recorded HR elevation spikes (non-exercise related), the sensitivity was 87.5%, specificity 62.2%, PPV 39.2%, NPV 92.3%, and overall accuracy 64.0% in the entire patient cohort. In the AF/AT recurrence only group, sensitivity was 87.6%, specificity 68.3%, PPV 53.6%, NPV 93.0%, and overall accuracy 75.0%. Conclusion: Consumer wearable devices have the potential to contribute to arrhythmia detection after AF ablation. Study Registration: ClinicalTrials.gov Identifier: NCT05037136 https://clinicaltrials.gov/ct2/show/NCT05037136.

Consumer wearable devices for evaluation of heart rate control using digoxin versus beta-blockers: the RATE-AF randomized trial.

Consumer-grade wearable technology has the potential to support clinical research and patient management. Here, we report results from the RATE-AF trial wearables study, which was designed to compare heart rate in older, multimorbid patients with permanent atrial fibrillation and heart failure who were randomized to treatment with either digoxin or beta-blockers. Heart rate (n = 143,379,796) and physical activity (n = 23,704,307) intervals were obtained from 53 participants (mean age 75.6 years (s.d. 8.4), 40% women) using a wrist-worn wearable linked to a smartphone for 20 weeks. Heart rates in participants treated with digoxin versus beta-blockers were not significantly different (regression coefficient 1.22 (95% confidence interval (CI) -2.82 to 5.27; P = 0.55); adjusted 0.66 (95% CI -3.45 to 4.77; P = 0.75)). No difference in heart rate was observed between the two groups of patients after accounting for physical activity (P = 0.74) or patients with high activity levels (≥30,000 steps per week; P = 0.97). Using a convolutional neural network designed to account for missing data, we found that wearable device data could predict New York Heart Association functional class 5 months after baseline assessment similarly to standard clinical measures of electrocardiographic heart rate and 6-minute walk test (F1 score 0.56 (95% CI 0.41 to 0.70) versus 0.55 (95% CI 0.41 to 0.68); P = 0.88 for comparison). The results of this study indicate that digoxin and beta-blockers have equivalent effects on heart rate in atrial fibrillation at rest and on exertion, and suggest that dynamic monitoring of individuals with arrhythmia using wearable technology could be an alternative to in-person assessment. ClinicalTrials.gov identifier: NCT02391337 .

Acute venous thromboembolic events in patients with monoclonal gammopathy of undetermined significance: An analysis of the National Inpatient Sample.

BACKGROUND: Monoclonal Gammopathy of Undetermined Significance (MGUS) is a premalignant plasma cell disorder which despite being clinically silent carries an increased risk of venous thromboembolism (VTE). We conducted a population-based study to investigate the risk of VTE in these patients. METHODS: We utilized the National Inpatient Sample (NIS) for the year 2016 to compare the incidence of acute VTE between patients who carry the diagnosis of MGUS and those who don't. We excluded hospitalizations with age < 18 years and those that had a diagnosed lymphoma, leukemia, solid malignancy, or other plasma cell dyscrasia. We utilized the ICD-10-CM coding system to search the database for codes of VTE, MGUS, and other comorbid conditions. Multivariate logistic regression models were used for comparative analysis adjusting for demographic characteristics and comorbidities. Baseline comorbidities were described as frequencies and proportions for categorical variables and as medians with interquartile ranges for continuous variables. RESULTS: A total of 33,115 weighted hospitalizations were included in the MGUS group. These were compared to 27,418,403 weighted hospitalizations without the diagnosis of MGUS. The MGUS group had higher odds of composite venous thromboembolism (adjusted OR 1.33, 95 % CI 1.22-1.44), deep vein thrombosis (adjusted OR 1.46, 95 % CI 1.29-1.65), and pulmonary embolism (adjusted OR 1.22, 95 % CI 1.09-1.37). CONCLUSION: Patients with MGUS had increased odds of developing acute venous thromboembolism compared to patients with no history of MGUS.

Maternal and prenatal outcomes of hemochromatosis in pregnancy: A population-based study.

BACKGROUND: This retrospective study investigated the impact of hemochromatosis on maternal and perinatal outcomes among delivery hospitalizations in the United States between 2010 and 2019, revealing notable trends and associations. METHODS: Utilizing data from over 36 million delivery hospitalizations, we conducted a comprehensive analysis, focusing on maternal complications, perinatal outcomes, and healthcare utilization among women with hemochromatosis compared to those without. RESULTS: Women with hemochromatosis exhibited a longer length of hospital stay (3.27 ± 0.20 days vs. 2.64 ± 0.04 days) and higher total hospital charges ($21,789.66 ± $1124.41 vs. $17,751.63 ± $97.71) compared to those without the condition. There was a significant increase in the prevalence of hemochromatosis among delivery hospitalizations over the studied period, from 1.91 per 100,000 hospitalizations to 8.65 cases per 100,000 hospitalizations. Hemochromatosis patients demonstrated a higher prevalence of hypertensive disorders of pregnancy (aOR: 1.50, 95 % CI: 1.03-2.19) and VTE(aOR: 20.35, 95 % CI: 5.05-82.05).There were no statistically significant differences in rates of peripartum hemorrhage, C-section, preterm birth, fetal growth restriction, large for gestational age infants, and fetal death between the two groups. CONCLUSIONS: Our findings underscore higher hypertensive disorders of pregnancy and VTE among women with hemochromatosis, despite unaffected perinatal outcomes. An increasing trend in hemochromatosis prevalence highlights the need for targeted interventions and cost-effective management strategies. Future research is needed to explore potential racial disparities and understand the rising incidence of hemochromatosis among pregnant women.

The Comparative Analysis of Single Plating Versus Double Plating in the Treatment of Unstable Bicondylar Proximal Tibial Plateau Fractures.

Introduction In the present study, we aimed to compare the clinical and radiological results of the single lateral locking plate fixation method to the dual plate (DP) fixation method in cases of unstable bicondylar proximal tibial plateau fractures. Materials and methods Fifty-six patients managed surgically with internal fixation for unstable bicondylar tibial plateau fractures (UBTF) (Schatzker type V and type VI or Arbeitsgemeinschaft für Osteosynthesefragen/Orthopaedic Trauma Association {AO/OTA} type 41-C) over 36 months from January 2017 to December 2020 were included in this prospective study. All the fractures were fixed surgically either using dual locking plates through double incisions (DP group) or with a single lateral locking plate (single plate {SP} group). All intraoperative and postoperative complications were assessed and recorded. Oxford Knee Score (OKS), Rasmussen's functional grading system, and Rasmussen's radiological scoring system were used to evaluate the functional and radiological outcomes. Result All of the patients were followed for at least 12 months. Twenty-six patients were fixed with a single lateral locking plate, and 30 patients were fixed with a double-incision dual locking plate. The mean Oxford Knee Score (OKS) was 43.24 ± 4.46 in the DP group and 42.7 ± 2.57 in the SP group (P = 0.544). The mean Rasmussen's functional score (RFS) score in the present study was 26.6 ± 2.21 in the DP group and 24.97 ± 3.92 in the SP group (P = 0.056). At the final follow-up, the mean Rasmussen's radiological score (RRS) was 9.06 ± 1.01 in the DP group and 8.1 ± 0.81 in the SP group (P = 0.0003). Conclusion There are no statistically significant differences in the functional outcomes between the two groups, but higher benefits were found in the radiological outcomes in the dual plating group as compared to single lateral locking plate group.

Prospective Comparative Study Between Proximal Femoral Nail vs. Screw Augmented Proximal Femoral Nail in Unstable Intertrochanteric Fractures of Femur.

Introduction The proximal femoral nail (PFN) is a widely accepted fixation method for the management of unstable intertrochanteric fractures. Reconstructing the lateral trochanteric wall and ensuring the stability of the trochanteric fragments are considered to be essential for enhancing the prognosis of unstable intertrochanteric fractures. The aim of this study is to evaluate and compare the results of the management of unstable intertrochanteric fracture of the femur using PFN and the screw-augmented PFN (aPFN). Methods This prospective comparative study was undertaken from January 2020 to July 2021 and included 60 patients presenting with unstable intertrochanteric fractures (AO/OTA type 31-A2.2 and 31-A2.3) at a tertiary care teaching institute in northern India. The enrolled patients were randomly divided into two groups (group 1 and group 2) and were managed with screw-augmented PFN and PFN, respectively. Functional outcome was evaluated using the Salvati and Wilson score at the 12-month follow-up. SPSS version 24.0 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. A p-value less than 0.05 was regarded as significant. Results The average time to union of the fractures in group 1 was 12.66 ± 1.68 weeks, while it was 13.47 ± 1.47 weeks in group 2 (p = 0.055). At the 12-month follow-up, the average functional outcome, as evaluated by Salvati and Wilson score, was 34 ± 2.40 in group 1, whereas it was 31.58 ± 4.4 in group 2; and the difference was observed to be statistically significant (p = 0.011). Group 1 had 28 patients (93.33%) with excellent to good results, while group 2 had 25 patients (83.33%) with excellent to good results. One patient in group 1 and five patients in group 2 had poor outcomes at the 12-month follow-up. Conclusion Screw-augmented PFN has better functional outcomes as compared to PFN alone for the management of unstable intertrochanteric fractures. Hence, in our opinion, screw augmentation of PFN may be the better fixation technique for most unstable intertrochanteric femur fractures.

Risk of second primary malignancy in patients with primary myelofibrosis: a SEER database study.

Prior studies report a greater incidence of second primary malignancy (SPM) among patients with myeloproliferative neoplasms, although the true risk in primary myelofibrosis (PMF) has not been elucidated. We utilized the Surveillance, Epidemiology, and End Results database to evaluate the risk of SPM in PMF patients and analyzed the effects of sociodemographic factors on the risk of SPM. Out of 5273 patients, 385 patients (7.30%) developed SPM. SPM occurred at SIR of 1.95 (95% CI 1.76-2.15) and AER of 149.01 per 10,000 population. A significantly higher incidence of melanoma (SIR 1.76, 95% CI 1.01-2.86), lymphoma (SIR 3.38, 95% CI 2.28-4.83), and leukemia (SIR 27.19, 95% CI 23.09-31.81) was observed. The risk was significantly higher in patients ≤60 years, males, chemotherapy recipients, within 5 years of PMF diagnosis, and for PMF diagnosed after 2009.

Smartphone detection of atrial fibrillation using photoplethysmography: a systematic review and meta-analysis.

OBJECTIVES: Timely diagnosis of atrial fibrillation (AF) is essential to reduce complications from this increasingly common condition. We sought to assess the diagnostic accuracy of smartphone camera photoplethysmography (PPG) compared with conventional electrocardiogram (ECG) for AF detection. METHODS: This is a systematic review of MEDLINE, EMBASE and Cochrane (1980-December 2020), including any study or abstract, where smartphone PPG was compared with a reference ECG (1, 3 or 12-lead). Random effects meta-analysis was performed to pool sensitivity/specificity and identify publication bias, with study quality assessed using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2) risk of bias tool. RESULTS: 28 studies were included (10 full-text publications and 18 abstracts), providing 31 comparisons of smartphone PPG versus ECG for AF detection. 11 404 participants were included (2950 in AF), with most studies being small and based in secondary care. Sensitivity and specificity for AF detection were high, ranging from 81% to 100%, and from 85% to 100%, respectively. 20 comparisons from 17 studies were meta-analysed, including 6891 participants (2299 with AF); the pooled sensitivity was 94% (95% CI 92% to 95%) and specificity 97% (96%-98%), with substantial heterogeneity (p<0.01). Studies were of poor quality overall and none met all the QUADAS-2 criteria, with particular issues regarding selection bias and the potential for publication bias. CONCLUSION: PPG provides a non-invasive, patient-led screening tool for AF. However, current evidence is limited to small, biased, low-quality studies with unrealistically high sensitivity and specificity. Further studies are needed, preferably independent from manufacturers, in order to advise clinicians on the true value of PPG technology for AF detection.

Improving the diagnosis of heart failure in patients with atrial fibrillation.

OBJECTIVE: To improve the echocardiographic assessment of heart failure in patients with atrial fibrillation (AF) by comparing conventional averaging of consecutive beats with an index-beat approach, whereby measurements are taken after two cycles with similar R-R interval. METHODS: Transthoracic echocardiography was performed using a standardised and blinded protocol in patients enrolled in the RATE-AF (RAte control Therapy Evaluation in permanent Atrial Fibrillation) randomised trial. We compared reproducibility of the index-beat and conventional consecutive-beat methods to calculate left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and E/e' (mitral E wave max/average diastolic tissue Doppler velocity), and assessed intraoperator/interoperator variability, time efficiency and validity against natriuretic peptides. RESULTS: 160 patients were included, 46% of whom were women, with a median age of 75 years (IQR 69-82) and a median heart rate of 100 beats per minute (IQR 86-112). The index-beat had the lowest within-beat coefficient of variation for LVEF (32%, vs 51% for 5 consecutive beats and 53% for 10 consecutive beats), GLS (26%, vs 43% and 42%) and E/e' (25%, vs 41% and 41%). Intraoperator (n=50) and interoperator (n=18) reproducibility were both superior for index-beats and this method was quicker to perform (p<0.001): 35.4 s to measure E/e' (95% CI 33.1 to 37.8) compared with 44.7 s for 5-beat (95% CI 41.8 to 47.5) and 98.1 s for 10-beat (95% CI 91.7 to 104.4) analyses. Using a single index-beat did not compromise the association of LVEF, GLS or E/e' with natriuretic peptide levels. CONCLUSIONS: Compared with averaging of multiple beats in patients with AF, the index-beat approach improves reproducibility and saves time without a negative impact on validity, potentially improving the diagnosis and classification of heart failure in patients with AF.

Impact of Renal Impairment on Beta-Blocker Efficacy in Patients With Heart Failure.

BACKGROUND: Moderate and moderately severe renal impairment are common in patients with heart failure and reduced ejection fraction, but whether beta-blockers are effective is unclear, leading to underuse of life-saving therapy. OBJECTIVES: This study sought to investigate patient prognosis and the efficacy of beta-blockers according to renal function using estimated glomerular filtration rate (eGFR). METHODS: Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials was performed. The authors report all-cause mortality on an intention-to-treat basis, adjusted for baseline covariates and stratified by heart rhythm. RESULTS: Median eGFR at baseline was 63 (interquartile range: 50 to 77) ml/min/1.73 m2; 4,584 patients (27.4%) had eGFR 45 to 59 ml/min/1.73 m2, and 2,286 (13.7%) 30 to 44 ml/min/1.73 m2. Over a median follow-up of 1.3 years, eGFR was independently associated with mortality, with a 12% higher risk of death for every 10 ml/min/1.73 m2 lower eGFR (95% confidence interval [CI]: 10% to 15%; p < 0.001). In 13,861 patients in sinus rhythm, beta-blockers reduced mortality versus placebo; adjusted hazard ratio (HR): 0.73 for eGFR 45 to 59 ml/min/1.73 m2 (95% CI: 0.62 to 0.86; p < 0.001) and 0.71 for eGFR 30 to 44 ml/min/1.73 m2 (95% CI: 0.58 to 0.87; p = 0.001). The authors observed no deterioration in renal function over time in patients with moderate or moderately severe renal impairment, no difference in adverse events comparing beta-blockers with placebo, and higher mortality in patients with worsening renal function on follow-up. Due to exclusion criteria, there were insufficient patients with severe renal dysfunction (eGFR <30 ml/min/1.73 m2) to draw conclusions. In 2,879 patients with atrial fibrillation, there was no reduction in mortality with beta-blockers at any level of eGFR. CONCLUSIONS: Patients with heart failure, left ventricular ejection fraction <50% and sinus rhythm should receive beta-blocker therapy even with moderate or moderately severe renal dysfunction.

Early Conversion of External Fixation to Interlocked Nailing in Open Fractures of Both Bone Leg Assisted with Vacuum Closure (VAC) - Final Outcome.

INTRODUCTION: Management of compound grade III fractures of both bone leg includes external stabilization for long period, followed by various soft tissue coverage procedures. Primary interlocking of tibia had been also done with variable results. External fixation for long time without any bone loss often leads to infected nonunion, loss of reduction, pin tract infection and failure of fixation, primary interlocking in compound grade III fractures had shown high medullary infection rate. We managed all cases of compound grade III A/B fractures with primary external fixation, simultaneous wound management using vacuum assisted closure (VAC) followed by early conversion to interlocking within 2 weeks of fixator application. AIM: To determine the effectiveness of vacuum assisted closure (VAC) for the early conversion of external fixator to definitive interlocking in open fractures of the both bone leg. MATERIALS AND METHODS: In current study we selected 84 cases of compound grade IIIA/B diaphyseal fractures of both bone leg during period of May 2010 to September 2013. We managed these cases by immediate debridement and application of external fixation followed by repeated debridement, application of vacuum assisted closure (VAC) and conversion to interlocking within two weeks. RESULTS: Out of 84 cases union was achieved in 80(95%) of cases with definitive tibial interlocking. Excellent to good result were obtained in 77(91.8%) of cases and fair to poor result seen in rest of 7(8.2%) of cases according to modified Ketenjian's criteria. 5 out of these 7 poor result group cases were from Compound Grade III B group to start with. Deep infection rate in our series were 7% i.e. total 6 cases and 4 out of these were from compound Grade III B group to start with. CONCLUSION: Vacuum assisted closure (VAC) give a good help for rapid closure of the wound and help in early conversion to definitive intramedullary nailing. Reamed nail could well be used in compound grade IIIA/B fractures without increasing the risk of infection. It gives better stability to fracture site and lessen the risk of implant failure.

Improving ECG Competence in Medical Trainees in a UK District General Hospital.

BACKGROUND: Competency in electrocardiogram (ECG) interpretation is central to undergraduate and postgraduate clinical training. Studies have demonstrated ECGs are interpreted sub-optimally. Our study compares the effectiveness of two learning strategies to improve competence and confidence. METHOD: A 1-month prospective randomized study compared the strategies in two cohorts: undergraduate third year medical students and postgraduate foundation year one (FY1) doctors. Both had blinded randomization to one of these learning strategies: focused teaching program (FTP) and self-directed learning (SDL). All volunteers completed a confidence questionnaire before and after allocation learning strategy and an ECG recognition multiple choice question (MCQ) paper at the end of the learning period. RESULTS: The FTP group of undergraduates demonstrated a significant difference in successfully interpreting "ventricular tachycardia" (P = 0.046) and "narrow complex tachycardia" (P = 0.009) than the SDL group. Participant confidence increased in both learning strategies. FTP confidence demonstrated a greater improvement than SDL for both cohorts. CONCLUSION: A dedicated teaching program can improve trainee confidence and competence in ECG interpretation. A larger benefit is observed in undergraduates and those undertaking a FTP.