Comparative non-persistence in the first year of treatment with oral anticoagulants in patients with atrial fibrillation: A French comprehensive nationwide study

BackgroundDirect oral anticoagulants (DOACs) were developed as an alternative to vitamin K antagonists (VKAs) and are commonly used for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Unlike VKAs, DOACs do not require Internal Normalized Ratio (INR) monitoring, but regular intake is as important for effective anticoagulation.ObjectivesThis study examined treatment persistence among patients receiving oral anticoagulants (OACs) for NVAF.MethodsWithin the French healthcare claims database (SNDS), we assessed and compared the rates of non-persistence (≥ 30-day treatment gap) among patients with NVAF initiating an OAC between January 2014 and December 2016. The time-to-event of non-persistence was computed and plotted using a cumulative incidence function accounting for the competing risk of mortality. After adjusting on confounding factors, the risk for non-persistence was compared between apixaban and each other OACs using a Cox proportional hazard model, or Fine and Gray models.ResultsIn a cohort of 321,501 OAC-naive patients with NVAF, the cumulative incidence of non-persistence at 12 months considering competing risk was 44.3%, 31.0%, 41.3% and 46.8% for VKAs, apixaban, rivaroxaban and dabigatran, respectively. Median therapy duration before non-persistence ranged between 70 and 121 days. Non-persistence was lower with apixaban compared with VKAs (HR = 0.63, 95%CI = [0.62–0.64]), rivaroxaban (HR = 0.71, 95%CI = [0.70–0.73]), and dabigatran (HR = 0.60, 95%CI = [0.59–0.62]).ConclusionsIn this nationwide observational study, non-persistence rates of oral anticoagulant treatment were high in patients treated for NVAF. Apixaban-treated patients seem to experience lowest discontinuation rates 12 months after treatment initiation compared to patients treated with any other OAC.     

Association between difference in blood pressure reduction and risk of cardiovascular events in a type 2 diabetes population: A meta-regression analysis

AimRecent US recommendations indicate a target blood pressure (BP) of 130/80 mmHg for patients with type 2 diabetes (T2D). Our aim was to characterize the association between risk of cardiovascular events and differences in BP decreases in randomized trials of a T2D population.MethodsA systematic search was made for randomized clinical trials assessing the effects of antihypertensive treatments in T2D patients on mortality, and fatal and non-fatal cardiovascular events, using a meta-regression technique to explore the influence of BP decreases on treatment effects.ResultsA total of 88,503 patients from 44 randomized trials were included. There was no significant association between BP decreases and risk of all-cause or cardiovascular mortality, cardiovascular events or myocardial infarction. However, stroke risk was influenced by BP decreases: compared with no reduction, a 10-mmHg reduction in systolic BP was associated with a relative odds ratio (OR) decrease of 33% (OR: 0.67, 95% CI: 0.54–0.82), and a 5-mmHg diastolic BP reduction was associated with a relative OR decrease of 38% (OR: 0.62, 95% CI: 0.50–0.76). Restricting the analysis to double-blind studies did not change the results for diastolic BP.ConclusionA reduction in BP lowers the risk of stroke, but does not appear to affect the risk of other cardiovascular events in a T2D population.     

Associations of serum magnesium levels and calcium–magnesium ratios with mortality in patients with coronary artery disease

AimsLow magnesium (Mg) and high calcium (Ca) levels are linked to increased cardiovascular disease (CVD) risk in the general population. This prospective study assessed whether there are any independent associations of serum Mg levels and Ca–Mg ratios with mortality in patients with coronary artery disease (CAD).MethodsThis prospective cohort study included 3380 CAD patients. Cox regression models were used to estimate associations of serum Mg and Ca–Mg ratio with risk of mortality.ResultsA total of 562 deaths (331 due to CVD) were recorded during a 7.59-year (median) follow-up. Spline plots displayed U-shaped associations between serum Mg levels and Ca–Mg ratios and risk of mortality. When compared with a moderate group, adjusted hazard ratios (95% confidence intervals) for low Mg levels and high Ca–Mg ratios were 1.59 (1.30–1.95) and 1.31 (1.06–1.61) for all-cause mortality, and 1.71 (1.32–2.22) and 1.44 (1.09–1.89) for CVD mortality, respectively. There was also a tendency to increase risk of mortality in patients with high serum Mg levels and low Ca–Mg ratios. Associations of low serum Mg and high Ca–Mg ratio with risk of mortality did not change when stratified by gender, body mass index, CAD type, estimated glomerular filtration rate, use of diuretics, or history of diabetes or hypertension.ConclusionThis study demonstrated that a moderate Ca–Mg ratio (range: 3.91–4.70) had the lowest mortality risk, and that low serum Mg and high Ca–Mg ratio were independent risk factors of mortality in CAD patients. Nevertheless, the optimal dose–response of Mg and Ca for mitigating CAD risk still requires further investigation.     

Impact of obesity on atrial fibrillation ablation

Central illustration. Summary of strategies to improve atrial fibrillation (AF) ablation outcomes in obese patients. BMI: body mass index; BS: bariatric surgery; CT: computed tomography; CV: cardiovascular; EAM: electro-anatomical mapping system; EAT: epicardial adipose tissue; MRI: magnetic resonance imaging; NOAC: non-vitamin K antagonist oral anticoagulant; PAF: paroxysmal atrial fibrillation; TOE: transoesophageal echocardiography; TTE: transthoracic echocardiography; US: ultrasound; VKA: vitamin K antagonist.

     

Clinical validation of an artificial intelligence algorithm offering cross-platform detection of atrial fibrillation using smart device electrocardiograms

BackgroundSeveral smart devices are able to detect atrial fibrillation automatically by recording a single-lead electrocardiogram, and have created a work overload at the hospital level as a result of the need for over-reads by physicians.AimTo compare the atrial fibrillation detection performances of the manufacturers’ algorithms of five smart devices and a novel deep neural network-based algorithm.MethodsWe compared the rate of inconclusive tracings and the diagnostic accuracy for the detection of atrial fibrillation between the manufacturers’ algorithms and the deep neural network-based algorithm on five smart devices, using a physician-interpreted 12-lead electrocardiogram as the reference standard.ResultsOf the 117 patients (27% female, median age 65 years, atrial fibrillation present at time of recording in 30%) included in the final analysis (resulting in 585 analyzed single-lead electrocardiogram tracings), the deep neural network-based algorithm exhibited a higher conclusive rate relative to the manufacturer algorithm for all five models: 98% vs. 84% for Apple; 99% vs. 81% for Fitbit; 96% vs. 77% for AliveCor; 99% vs. 85% for Samsung; and 97% vs. 74% for Withings (P < 0.01, for each model). When applying our deep neural network-based algorithm, sensitivity and specificity to correctly identify atrial fibrillation were not significantly different for all assessed smart devices.ConclusionIn this clinical validation, the deep neural network-based algorithm significantly reduced the number of tracings labeled inconclusive, while demonstrating similarly high diagnostic accuracy for the detection of atrial fibrillation, thereby providing a possible solution to the data surge created by these smart devices.     

Unsupervised clustering of patients with severe aortic stenosis: A myocardial continuum

BackgroundTraditional statistics, based on prediction models with a limited number of prespecified variables, are probably not adequate to provide an appropriate classification of a condition that is as heterogeneous as aortic stenosis (AS).AimsTo investigate a new classification system for severe AS using phenomapping.MethodsConsecutive patients from a referral centre (training cohort) who met the echocardiographic definition of an aortic valve area (AVA) ≤ 1 cm² were included. Clinical, laboratory and imaging continuous variables were entered into an agglomerative hierarchical clustering model to separate patients into phenogroups. Individuals from an external validation cohort were then assigned to these original clusters using the K nearest neighbour (KNN) function and their 5-year survival was compared after adjustment for aortic valve replacement (AVR) as a time-dependent covariable.ResultsIn total, 613 patients were initially recruited, with a mean ± standard deviation AVA of 0.72 ± 0.17 cm². Twenty-six variables were entered into the model to generate a specific heatmap. Penalized model-based clustering identified four phenogroups (A, B, C and D), of which phenogroups B and D tended to include smaller, older women and larger, older men, respectively. The application of supervised algorithms to the validation cohort (n = 1303) yielded the same clusters, showing incremental cardiac remodelling from phenogroup A to phenogroup D. According to this myocardial continuum, there was a stepwise increase in overall mortality (adjusted hazard ratio for phenogroup D vs A 2.18, 95% confidence interval 1.46–3.26; P < 0.001).ConclusionsArtificial intelligence re-emphasizes the significance of cardiac remodelling in the prognosis of patients with severe AS and highlights AS not only as an isolated valvular condition, but also a global disease.     

Prevalence of liver fibrosis in an unselected general population with high prevalence of obesity and diabetes mellitus. Time for screening?

IntroductionCirrhosis and liver cancer are currently common causes of death worldwide. The global epidemic of obesity has increased the incidence of nonalcoholic fatty liver disease (NAFLD) and cirrhosis in recent years. Advanced fibrosis increases the morbimortality rate in NAFLD. The Mexican population has one of the highest prevalence of obesity and diabetes mellitus (DM) worldwide.AimTo determine the prevalence of advanced liver fibrosis in Mexican general population.MethodsAdult individuals, without a history of liver disease nor heavy alcohol consumption were randomly sampled from 20,919 participants of a health and nutrition survey applied to the general population. Clinical and laboratory evaluations were performed to calculate the NAFLD fibrosis score (NFS) (an extensively validated non-invasive method). Two cut-off points were used. Advanced fibrosis was defined as a result >0.676.ResultsIn total 695 individuals were included. The mean age was 47.8 ± 16.4. The majority were between 20 and 50 years (59%), 70.2% were female, 35.5% showed obesity and 15.8% DM. The 93% had normal serum ALT. Based on the NFS results, 56 individuals (8.1%) had a high probability of fibrosis. Most patients from this subgroup showed normal serum ALT (92.9%), 89.3% were >45 yr. old, 52% were obese and 27% suffered from DM.ConclusionsBased on these results, 8.1% of Mexican general population without a history of liver disease is at high risk of having advanced liver fibrosis and complications and death derived from cardiovascular disease and cirrhosis. Most of them showed normal ALT serum levels.     

Structural Cardiac Remodeling in Atrial Fibrillation

ObjectivesThis study sought to evaluate preablation computed tomography angiography (CTA) for atrial and epicardial features to predict atrial fibrillation (AF) recurrence after ablation.BackgroundStructural atrial remodeling is a process associated with occurrence or persistence of AF. Different anatomical imaging features have been proposed to influence atrial remodeling both negatively and positively as substrate for AF.MethodsPatients with nonvalvular AF underwent cardiac CTA before pulmonary vein isolation at 2 high-volume centers. Left atrial (LA) and right atrial volumes, LA wall thickness (LAWT), and epicardial adipose tissue volume and attenuation were evaluated. Additional subanalyses of electroanatomical maps were made. Follow-up was performed for at least 12 months, including subanalysis of repeated cardiac CTA studies. Interrater variability was assessed.ResultsOf 732 patients, 270 (36.9%) had AF recurrence after a mean of 7 months. CT analysis revealed larger indexed LA volume (47.3 mL/m² vs 43.6 mL/m²; P = 0.0001) and higher mean anterior (1.91 mm vs 1.65 mm; P < 0.0001) and posterior (1.61 mm vs 1.39 mm; P = 0.001) LAWT in patients with AF recurrence. Epicardial adipose tissue volume in patients with AF recurrence was higher (144.5 mm³ vs 128.5 mm³; P < 0.0001) and further progressed significantly in a subset of 85 patients after 2 years (+11.8 mm² vs −3.5 mm²; P = 0.041). Attenuation levels were lower, indicating a higher lipid component associated with AF recurrence (−69.1 HU vs −67.5 HU; P = 0.001). A total of 103 atrial voltage maps were highly predictive of AF recurrence and showed good discriminatory power for patients with low voltage >50% and LAWT (1.55 ± 0.5 mm vs 1.81 ± 0.6 mm; P = 0.032). Net reclassification improvement (NRI) showed a significant incremental benefit (NRI = 0.279; P < 0.0001) when adding LAWT to established risk models.ConclusionsAtrial wall thickness, epicardial fat volume, and attenuation are associated with AF recurrence in patients undergoing ablation therapy.     

Minimal agreement between basophil activation test and immunoassay in diagnosis of penicillin allergy

IntroductionBasophil activation test (BAT) and immunoassays are the most widely used in vitro tests to diagnose IgE-mediated allergic reactions to penicillin. However, studies to determine if one test is interdependent from another are limited.ObjectiveThe present study aimed to measure the agreement between BAT and immunoassay in diagnosis of penicillin allergy.MethodBAT was performed using penicillin G (Pen G), penicillin V (Pen V), penicilloyl-polylysine (PPL), minor determinant mix (MDM), amoxicillin (Amx) and ampicillin (Amp) in 25 patients. Immunoassay of total IgE (tIgE) and specific IgE (sIgE) antibodies to Pen G, Pen V, Amx and Amp were quantified. Skin prick test (SPT) using PPL-MDM, Amx, Amp and Clavulanic acid were also performed.ResultsMinimal agreement was observed between BAT and immunoassay (k = 0.25). Of two BAT-positive patients, one patient is positive to Amx (59.27%, SI = 59) and Amp (82.32%, SI = 82) but sIgE-negative to all drug tested. This patient is also SPT-positive to both drugs. Another patient is BAT-positive to Pen G (10.18%, SI = 40), Pen V (25.07%, SI = 100) and Amp (19.52%, SI = 79). In sIgE immunoassay, four patients were sIgE-positive to at least one of the drugs tested. The sIgE level of three patients was between low and moderate and they were BAT-negative. One BAT-positive patient had a high level of sIgE antibodies (3.50–17.5 kU/L) along with relatively high specific to total IgE ratio ≥0.002 (0.004–0.007).ConclusionsThe agreement between BAT and immunoassay is minimal. Performing both tests provides little increase in the sensitivity of allergy diagnosis work-up for immediate reactions to penicillin.     

Higher liver stiffness scores are associated with early kidney dysfunction in patients with histologically proven non-cirrhotic NAFLD

AimThe association between Liver fibrosis (LF), as assessed by either histology or Liver stiffness measurement (LSM), and the presence of Early kidney dysfunction (EKD) was investigated in this study, as was also the diagnostic performance of LSM for identifying the presence of EKD in patients with Non-alcoholic fatty liver disease (NAFLD).Materials and methodsA total of 214 adults with non-cirrhotic biopsy-proven NAFLD were recruited from two independent medical centres. Their histological stage of LF was quantified using Brunt's criteria. Vibration-controlled Transient elastography (TE), using M-probe (FibroScan®) ultrasound, was performed in 154 patients and defined as significant when LSM was ≥ 8.0 kPa. EKD was defined as the presence of microalbuminuria with an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m². Logistic regression modelling was used to estimate the likelihood of having EKD with NAFLD (LSM–EKD model).ResultsThe prevalence of EKD was higher in patients with vs without LF on histology (22.14% vs 4.82%, respectively; P < 0.001) and, similarly, EKD prevalence was higher in patients with LSM ≥ 8.0 kPa vs LSM < 8.0 kPa (23.81% vs 6.59%, respectively; P < 0.05). The area under the ROC curve of the LSM–EKD model for identifying EKD was 0.80 (95% CI: 0.72–0.89). LF detected by either method was associated with EKD independently of established renal risk factors and potential confounders.ConclusionLF was independently associated with EKD in patients with biopsy-proven NAFLD. Thus, TE-measured LSM, a widely used technique for quantifying LF, can accurately identify those patients with NAFLD who are at risk of having EKD.