Critical appraisal of technologies to assess electrical activity during atrial fibrillation: a position paper from the European Heart Rhythm Association and European Society of Cardiology Working Group on eCardiology in collaboration with the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society and Computing in Cardiology

We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter–electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future

Dickkopf-1 (Dkk-1) in plasma and synovial fluid is inversely correlated with radiographic severity of knee osteoarthritis patients

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is a common degenerative joint disease causing pain, stiffness, reduced motion, swelling, crepitus, and disability. Dickkopf-1 (Dkk-1) is a critical mediator of osteoblastogenesis and regulates the joint remodeling. The aim of this study was to examine plasma and synovial fluid Dkk-1 levels of patients with primary knee OA and to investigate their relationship with disease severity.</p> <p>Methods</p> <p>Thirty-five patients aged 55-83 years with knee OA and 15 healthy individuals were recruited into this study. Disease severity was determined using weight-bearing anteroposterior radiographs of the affected knee. The radiological grading of OA in the knee was performed according to the Kellgren-Lawrence grading system. Dkk-1 levels in both plasma and synovial fluid were evaluated using enzyme-linked immunosorbent assay.</p> <p>Results</p> <p>The average concentration of circulating Dkk-1 in the knee OA patients was remarkably lower than that of healthy controls (396.0 ± 258.8, 95%CI 307.1-484.9 vs 2348.8 ± 2051.5, 95%CI 1164.3-3533.3 pg/ml, p < 0.0001). Dkk-1 levels in synovial fluid were significantly lower than in paired plasma samples (58.6 ± 31.8, 95%CI 47.7-69.6 vs 396.0 ± 258.8, 95%CI 307.1-484.9 pg/ml, p < 0.001). Furthermore, both plasma and synovial fluid Dkk-1 levels were inversely correlated with radiographic severity (r = -0.78, p < 0.001 and r = -0.42, p = 0.01, respectively). Plasma Dkk-1 levels were also significantly correlated with synovial fluid Dkk-1 levels (r = 0.72, p < 0.001).</p> <p>Conclusions</p> <p>Dkk-1 levels in plasma and synovial fluid are inversely related to the severity of joint damage in knee OA. Dkk-1 could serve as a biochemical marker for determining disease severity and might play a potential role in the pathogenesis of the degenerative process of OA.</p

Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational cohort study

Background: Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and β blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and β blockers in patients with HFrEF. Methods: We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and β blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF. Findings: Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p&lt;0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p&lt;0·0001) and heights (162 [7] cm vs 174 [8] cm, p&lt;0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and β blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and β blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and β blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels. Interpretation: This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and β blockers than men, and brings into question what the true optimal medical therapy is for women versus men

Reno-protective effects of renin–angiotensin system blockade in type 2 diabetic patients: a systematic review and network meta-analysis

AIMS/HYPOTHESIS: This meta-analysis aimed to compare the renal outcomes between ACE inhibitor (ACEI)/angiotensin II receptor blocker (ARB) and other antihypertensive drugs or placebo in type 2 diabetes. METHODS: Publications were identified from Medline and Embase up to July 2011. Only randomised controlled trials comparing ACEI/ARB monotherapy with other active drugs or placebo were eligible. The outcome of end-stage renal disease, doubling of serum creatinine, microvascular complications, microalbuminuria, macroalbuminuria and albuminuria regression were extracted. Risk ratios were pooled using a random-effects model if heterogeneity was present; a fixed-effects model was used in the absence of heterogeneity. RESULTS: Of 673 studies identified, 28 were eligible (n = 13-4,912). In direct meta-analysis, ACEI/ARB had significantly lower risk of serum creatinine doubling (pooled RR = 0.66 [95% CI 0.52, 0.83]), macroalbuminuria (pooled RR = 0.70 [95% CI 0.50, 1.00]) and albuminuria regression (pooled RR 1.16 [95% CI 1.00, 1.39]) than other antihypertensive drugs, mainly calcium channel blockers (CCBs). Although the risks of end-stage renal disease and microalbuminuria were lower in the ACEI/ARB group (pooled RR 0.82 [95% CI 0.64, 1.05] and 0.84 [95% CI 0.61, 1.15], respectively), the differences were not statistically significant. The ACEI/ARB benefit over placebo was significant for all outcomes except microalbuminuria. A network meta-analysis detected significant treatment effects across all outcomes for both active drugs and placebo comparisons. CONCLUSIONS/INTERPRETATION: Our review suggests a consistent reno-protective effect of ACEI/ARB over other antihypertensive drugs, mainly CCBs, and placebo in type 2 diabetes. The lack of any differences in BP decrease between ACEI/ARB and active comparators suggest this benefit is not due simply to the antihypertensive effect

Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis

The central nervous system (CNS) is capable of gathering information on the body’s nutritional state and it implements appropriate behavioral and metabolic responses to changes in fuel availability. This feedback signaling of peripheral tissues ensures the maintenance of energy homeostasis. The hypothalamus is a primary site of convergence and integration for these nutrient-related feedback signals, which include central and peripheral neuronal inputs as well as hormonal signals. Increasing evidence indicates that glucose and lipids are detected by specialized fuel-sensing neurons that are integrated in these hypothalamic neuronal circuits. The purpose of this review is to outline the current understanding of fuel-sensing mechanisms in the hypothalamus, to integrate the recent findings in this field, and to address the potential role of dysregulation in these pathways in the development of obesity and type 2 diabetes mellitus

A prospective randomized study to assess the efficacy of rate and site of atrial pacing on long-term development of atrial fibrillation

Septal Pacing and Atrial Fibrillation Suppression. The Septal Pacing for Atrial Fibrillation Suppression Evaluation (SAFE) study is a single-blinded, parallel randomized designed multicenter study in pacemaker indicated patients with paroxysmal atrial fibrillation (AF). The objective is to evaluate whether the site of atrial pacing - conventional right atrial appendage versus low atrial septal - with or without atrial overdrive pacing will influence the development of persistent AF. The study will provide a definitive answer to whether a different atrial pacing site or the use of AF suppression pacing or both can give incremental antiarrhythmic benefit when one is implanting a device for a patient with a history of paroxysmal AF. (J Cardiovasc Electrophysiol, Vol. 20, pp. 1020-1025) © 2009 Wiley Periodicals, Inc.link_to_subscribed_fulltex

Regional Variation of Mortality in Heart Failure With Reduced and Preserved Ejection Fraction Across Asia: Outcomes in the ASIAN-HF Registry

10.1161/JAHA.119.012199Journal of the American Heart Association91e01219

Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial

Background: The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. Methods: In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had �2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. Conclusion: The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS. © 2021 Elsevier Inc

Impact of bone marker feedback on adherence to once monthly ibandronate for osteoporosis among Asian postmenopausal women

Aim: his study assesses the impact of serum carboxy-terminal collagen crosslinks (CTX) bone marker feedback (BMF) on adherence to ibandronate treatment in Asian postmenopausal women with osteoporosis. Methods: This was a 12-month (6-monthly phased), randomized, prospective, open-label, multi-center study conducted in 596 (of 628 enrolled) postmenopausal women with osteoporosis (≤ 85 years old) who were naïve, lapsed, or current bisphosphonate users. Patients were randomized into two arms: serum CTX BMF at 3 months versus no-BMF. Once-monthly 150 mg ibandronate tablet was administered for 12 months and adherence to therapy was assessed at 6 and 12 months. In addition, patient satisfaction and safety of ibandronate treatment were also assessed. Results: Serum CTX BMF at 3 months showed no impact on adherence. The proportions of adherent patients were comparable in the BMF versus no-BMF arms (92.6% vs. 96.0%, P = 0.16); overall, serum CTX levels were similar for adherent and non-adherent patients. However, BMF patients felt more informed about their osteoporosis (P < 0.001) and more satisfied (P < 0.01) than no-BMF patients. Conclusions: The Asian postmenopausal osteoporosis patients in this study had a high adherence rate to once-monthly ibandronate therapy. Use of serum CTX BMF had no further impact on increasing adherence, but increased treatment satisfaction. © 2009 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.link_to_subscribed_fulltex

Critical appraisal of technologies to assess electrical activity during atrial fibrillation: a position paper from the European Heart Rhythm Association and European Society of Cardiology Working Group on eCardiology in collaboration with the Heart Rhythm Society, Asia Pacific Heart Rhythm Society, Latin American Heart Rhythm Society and Computing in Cardiology

We aim to provide a critical appraisal of basic concepts underlying signal recording and processing technologies applied for (i) atrial fibrillation (AF) mapping to unravel AF mechanisms and/or identifying target sites for AF therapy and (ii) AF detection, to optimize usage of technologies, stimulate research aimed at closing knowledge gaps, and developing ideal AF recording and processing technologies. Recording and processing techniques for assessment of electrical activity during AF essential for diagnosis and guiding ablative therapy including body surface electrocardiograms (ECG) and endo- or epicardial electrograms (EGM) are evaluated. Discussion of (i) differences in uni-, bi-, and multi-polar (omnipolar/Laplacian) recording modes, (ii) impact of recording technologies on EGM morphology, (iii) global or local mapping using various types of EGM involving signal processing techniques including isochronal-, voltage- fractionation-, dipole density-, and rotor mapping, enabling derivation of parameters like atrial rate, entropy, conduction velocity/direction, (iv) value of epicardial and optical mapping, (v) AF detection by cardiac implantable electronic devices containing various detection algorithms applicable to stored EGMs, (vi) contribution of machine learning (ML) to further improvement of signals processing technologies. Recording and processing of EGM (or ECG) are the cornerstones of (body surface) mapping of AF. Currently available AF recording and processing technologies are mainly restricted to specific applications or have technological limitations. Improvements in AF mapping by obtaining highest fidelity source signals (e.g. catheter-electrode combinations) for signal processing (e.g. filtering, digitization, and noise elimination) is of utmost importance. Novel acquisition instruments (multi-polar catheters combined with improved physical modelling and ML techniques) will enable enhanced and automated interpretation of EGM recordings in the near future