More species in the world are threatened with extinction today than at any other time in recent history. In 2005, the Alliance for Zero Extinction (AZE; https://zeroextinction.org/) released its ...first inventory of highly threatened species (i.e., those listed as Critically Endangered or Endangered on the IUCN Red List) that are effectively confined to a single site. Updates were released in 2010 and 2018. Here we identify the species removed from the list in these updates, determine the reasons for these removals, identify species that no longer qualify as AZE species as a result of conservation actions, and examine which conservation actions produced these recoveries. In total, 360 species that qualified as AZE species in 2005 no longer qualified by 2018 (45% of those listed in 2005) due to improved knowledge of distribution or taxonomy (83%), genuine improvements resulting in species being downlisted to lower categories of extinction risk (12%), genuine range expansion of species such that they are no longer restricted to single sites (4%), or deterioration to extinction (1%). Our results show that while protected areas and site management are important to the successful conservation of AZE species, other conservation actions, such as species‐level management or improved laws and policies, are also essential to safeguard these species from extinction. Sixty‐eight percent of the original 2005 AZE sites are now fully or partially covered by protected areas, an increase of almost 20% in 15 years. Yet today, only 64% of current (2018) AZE sites are fully or partially covered by protected areas, with 36% lacking any formal protection. Continued efforts to safeguard and manage AZE sites would benefit not only the 1,483 AZE species but also potentially another 1,359 Critically Endangered and Endangered amphibian, bird, and mammal species whose distributions overlap with AZE sites.
By 2018 Alliance for Zero Extinction 360 species that qualified as AZE species in 2005 no longer qualified (45% of those listed in 2005) due to improved knowledge of distribution or taxonomy (81%), genuine improvements resulting lower categories of extinction risk (12%), genuine range expansion of species (6%), or deterioration to extinction (1%). While protected areas and site management are important to the successful conservation of AZE species, other conservation actions, such as species‐level management or improved laws and policies, are also essential to safeguard these species from extinction. Sixty‐eight percent of the original 2005 AZE sites are now fully or partially covered by protected areas, an increase of almost 20% in 15 years. Yet today, only 64% of current (2018) AZE sites are fully or partially covered by protected areas, with 36% lacking any formal protection.
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.
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.
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.
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.
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.
To compare low-dose ...digoxin with bisoprolol (a β-blocker).
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.
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).
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.
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.
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.
ClinicalTrials.gov Identifier: NCT02391337 and clinicaltrialsregister.eu Identifier: 2015-005043-13.
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 β-blocker efficacy in patients with sinus rhythm and atrial fibrillation.
Neural network-based variational autoencoders and hierarchical clustering were applied to pooled individual patient data from nine double-blind, randomised, placebo-controlled trials of β 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).
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 β 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 β 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 β 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.
An artificial intelligence-based clustering approach was able to distinguish prognostic response from β 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 β blockers did reduce mortality.
Medical Research Council, UK, and EU/EFPIA Innovative Medicines Initiative BigData@Heart.
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.
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.
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.
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.
Abstract
Background
The RAte control Therapy Evaluation in permanent AF trial (RATE-AF; NCT02391337) was the first head-to-head controlled trial of beta-blockers versus digoxin in patients with ...permanent atrial fibrillation (AF) and symptoms of heart failure. Patients randomised to digoxin had similar physical-related quality of life and heart rate, with significantly improved functional class, reduced N-terminal pro-brain natriuretic peptide (NT-proBNP) and substantially less adverse events. The impact of rate control therapy on measures of cardiac function is not currently understood.
Purpose
To compare the effect of digoxin versus beta-blockers on systolic and diastolic cardiac function according to heart failure sub-type.
Methods
Blinded echocardiograms assessing systolic and diastolic function were performed at baseline and 12 month follow-up, using a robust method to account for rhythm irregularity (average of three index-beats acquired in appropriate cardiac cycles). Outcomes were the change in left-ventricular ejection fraction (LVEF), systolic tissue Doppler velocity (s'), stroke volume, global longitudinal strain (GLS), diastolic tissue Doppler (e'), mitral E wave deceleration time, E/e', pulmonary vein diastolic deceleration time, isovolumic relaxation time and left atrial ejection fraction. Analyses were stratified by baseline LVEF (≥50%, 40–50% and <40%).
Results
160 patients were randomised, of which 145 patients survived to 12-month follow-up with median age 75 years (IQR 69–82) and 44% women. Median baseline heart rate was 96 beats/min (IQR 86–112), blood pressure 135/85 mmHg (IQR 124/77–146/91), NTproBNP 1049 pg/mL (744–1463) and mean NYHA class 2.4 (SD 0.6). In 119 patients with LVEF ≥50% at baseline, diastolic and systolic parameters improved over time with digoxin therapy. There was a significantly greater improvement in systolic function in 63 patients on digoxin compared to 67 with beta-blockers; Figure 1. Patients randomised to digoxin had a higher LVEF at follow-up (adjusted mean difference AMD 2.3%, 95% CI 0.3–4.2; p=0.021), higher s' (1.1cm/s, 1.0–1.2; p=0.003) and higher stroke volume (6.5mL, 0.4–12.6; p=0.037) compared to beta-blockers, without any difference in diastolic parameters (Figure 2). In 16 patients with LVEF 40–50% at baseline, s' significantly increased with digoxin compared to beta-blockers (AMD 1.5 cm/s, 1.2–1.7; p=0.001), with no difference for other systolic or diastolic parameters. 10 patients with LVEF <40% at baseline showed no difference between digoxin and beta-blockers for any echocardiographic measures.
Conclusion
Patients randomised to digoxin with permanent AF, heart failure symptoms and preserved LVEF have significantly greater improvement in multiple parameters of systolic function compared to conventional treatment with beta-blockers.
Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): National Institute of Health Research
Graphical Abstract
Graphical Abstract
Step-wise workflow to improve the value of artificial intelligence in clinical research. AI, artificial intelligence.
Abstract
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.
Abstract
Introduction
Early diagnosis of atrial fibrillation (AF) is essential to reduce complications such as stroke, and improve patient quality of life. Novel screening techniques using smartphone ...camera photoplethysmography (PPG) can be used for AF detection, but their clinical applicability remains unclear.
Purpose
To assess the diagnostic accuracy of smartphone PPG compared to conventional ECG for AF detection.
Methods
We performed a systematic review of MEDLINE, EMBASE, Cochrane library, and other databases (1980-October 2019), including any study or abstract where smartphone finger-tip PPG was compared with a reference ECG (1, 3 or 12-lead). Outcomes were sensitivity (SE), specificity (SP), positive and negative predictive value (PPV; NPV) and overall accuracy. Bivariate hierarchical random effects meta-analysis was performed for studies with confidence intervals for SE and SP, and funnel plots were used to identify publication bias. Study quality was assessed using the established QUADAS-2 tool by two independent graders.
Results
1350 publications were screened, of which 17 studies were included in the systematic review (7 full text publications and 10 abstracts), providing 21 comparisons of accuracy for AF detection. Most studies were based in secondary care and small (range n=33 to 1095), with a total of 5469 participants including 1384 with AF. Only 4 studies were multicentre. Smartphone applications used were Cardiio Rhythm, Fibricheck, Preventicus and Heartbeats, with 7 studies not specifying the tool used. Overall SE and SP for AF detection were high, ranging from 76 to 100%, and 85 to 100% respectively. PPV ranged from 54 to 100% and NPV from 77 to 100%, with overall accuracy between 61 and 99%. The meta-analysis included 12 comparisons from 10 studies (n=2714; 936 with AF). The pooled SE was 93% (95% CI 90–96%) and SP 97% (95% CI 95–99%); Figure 1A. QUADAS-2 assessment demonstrated poor quality of studies overall, with a high or unclear risk of bias in at least one domain for all studies. There was clear evidence of publication bias; Figure 1B.
Conclusions
PPG offers the potential for large scale, non-invasive, patient-led screening of AF. However, current evidence is limited to biased, low quality studies often with unrealistic results for AF detection. These are insufficient to advise clinicians on the true value of current smartphone PPG technology.
Figure 1. Meta-analysis & publication bias
Funding Acknowledgement
Type of funding source: Public grant(s) – EU funding. Main funding source(s): BigData@Heart EU/EFPIA IMI 116074.
Abstract
Introduction
Echocardiography is essential for the management of patients with atrial fibrillation (AF), but current methods are time consuming and lack any evidence of reproducibility.
...Purpose
To compare conventional averaging of consecutive beats with an index beat approach, where systolic and diastolic measurements are taken once after two prior beats with a similar RR interval (not more than 60 ms difference).
Methods
Transthoracic echocardiography was performed using a standardized and blinded protocol in patients enrolled into the RAte control Therapy Evaluation in permanent AF randomised controlled trial (RATE-AF; NCT02391337). AF was confirmed in all patients with a preceding 12-lead ECG. A minimum of 30-beat loops were recorded. Left ventricular function was determined using the recommended averaging of 5 and 10 beats and using the index beat method, with observers blinded to clinical details. Complete loops were used to calculate the within-beat coefficient of variation (CV) and intraclass correlation coefficient (ICC) for Simpson's biplane left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and filling pressure (E/e').
Results
160 patients (median age 75 years (IQR 69–82); 46% female) were included, with median heart rate 100 beats/min (IQR 86–112). For LVEF, the index beat had the lowest CV of 32% compared to 51% for 5 consecutive beats and 53% for 10 consecutive beats (p<0.001). The index beat also had the lowest CV for GLS (26% versus 43% and 42%; p<0.001) and E/e' (25% versus 41% and 41%; p<0.001; see Figure for ICC comparison). Intra-operator reproducibility, assessed by the same operator from two different recordings in 50 patients, was superior for the index beat with GLS bias −0.5 and narrow limits of agreement (−3.6 to 2.6), compared to −1.0 for 10 consecutive beats (−4.0 to 2.0). For inter-operator variability, assessed in 18 random patients, the index beat also showed the smallest bias with narrow confidence intervals (CI). Using a single index beat did not impact on the validity of LVEF, GLS or E/e' measurement when correlated with natriuretic peptides. Index beat analysis substantially shortened analysis time; 35 seconds (95% CI 35 to 39 seconds) for measuring E/e' with the index beat versus 98 seconds (95% CI 92 to 104 seconds) for 10 consecutive beats (see Figure).
Conclusion
Index beat determination of left ventricular function improves reproducibility, saves time and does not compromise validity compared to conventional quantification in patients with heart failure and AF. After independent validation, the index beat method should be adopted into routine clinical practice.
Comparison for measurement of E/e'
Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institute of Health Research UK
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