Atrial fibrillation progression risk factors and associated cardiovascular outcome in well-phenotyped patients:data from the AF-RISK study

Aims: Atrial fibrillation (AF) is a progressive disease, but identifying patients at risk for AF progression is challenging. We aimed to identify factors associated with AF progression. Methods and results: Atrial fibrillation progression was assessed in 392 patients with recent-onset paroxysmal or persistent AF included in the prospective, observational, multicentre identification of a risk profile to guide atrial fibrillation (AF-RISK) study. Progression of AF was assessed by Holter monitoring and 2-week event recorder at baseline and 1-year follow-up. AF progression was defined as: (i) doubling in AF burden at 1 year compared to baseline with a minimum AF burden of 10% in paroxysmal AF; or (ii) transition from paroxysmal to persistent or permanent AF; or (iii) persistent to permanent AF. Age was 60 ± 11 years, 62% were men, and 83% had paroxysmal AF. At 1 year, 52 (13%) had AF progression (11% in paroxysmal; 26% in persistent AF). Multivariable logistic regression showed that left atrial volume [odds ratio (OR) per 10 mL 1.251, 95% confidence interval (CI) 1.078-1.450; P < 0.001], N-terminal pro-B-type natriuretic peptide (NT-proBNP; OR per standard deviation increase 1.583, 95% CI 1.099-2.281; P = 0.014), and plasminogen activator inhibitor-1 (PAI-1; OR per standard deviation increase 0.660, 95% CI 0.472-0.921; P = 0.015) were associated with AF progression. In an additional follow-up of 1.9 (0.9-3.3) years patients with AF progression developed more cardiovascular events and all-cause mortality (12.4%/year vs. 2.3%/year, P < 0.001). Conclusion: Atrial fibrillation progression occurred in 13% of patients with recent-onset AF during 1-year follow-up. Left atrial volume, NT-proBNP, and PAI-1 were associated with AF progression. Patients with AF progression had a higher event rate. Trial registration number: Clinicaltrials.gov NCT01510210

Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma Severity

PurposeTo evaluate whether a chromatic pupillometry test can be used to detect impaired function of intrinsically photosensitive retinal ganglion cells (ipRGCs) in patients with primary open-angle glaucoma (POAG) and to determine if pupillary responses correlate with optic nerve damage and visual loss.DesignCross-sectional study.ParticipantsOne hundred sixty-one healthy controls recruited from a community polyclinic (55 men; 151 ethnic Chinese) and 40 POAG patients recruited from a glaucoma clinic (22 men; 35 ethnic Chinese) 50 years of age or older.MethodsSubjects underwent monocular exposure to narrowband blue light (469 nm) or red light (631 nm) using a modified Ganzfeld dome. Each light stimulus was increased gradually over 2 minutes to activate sequentially the rods, cones, and ipRGCs that mediate the pupillary light reflex. Pupil diameter was recorded using an infrared pupillography system.Main Outcome MeasuresPupillary responses to blue light and red light were compared between control subjects and those with POAG by constructing dose-response curves across a wide range of corneal irradiances (7–14 log photons/cm2 per second). In patients with POAG, pupillary responses were evaluated relative to standard automated perimetry testing (Humphrey Visual Field [HVF]; Carl Zeiss Meditec, Dublin, CA) and scanning laser ophthalmoscopy parameters (Heidelberg Retinal Tomography [HRT]; Heidelberg Engineering, Heidelberg, Germany).ResultsThe pupillary light reflex was reduced in patients with POAG only at higher irradiance levels, corresponding to the range of activation of ipRGCs. Pupillary responses to high-irradiance blue light associated more strongly with disease severity compared with responses to red light, with a significant linear correlation observed between pupil diameter and HVF mean deviation (r = −0.44; P = 0.005) as well as HRT linear cup-to-disc ratio (r = 0.61; P < 0.001) and several other optic nerve head parameters.ConclusionsIn glaucomatous eyes, reduced pupillary responses to high-irradiance blue light were associated with greater visual field loss and optic disc cupping. In POAG, a short chromatic pupillometry test that evaluates the function of ipRGCs can be used to estimate the degree of damage to retinal ganglion cells that mediate image-forming vision. This approach could prove useful in detecting glaucoma

Clinical and electrophysiological predictors of device-detected new-onset atrial fibrillation during 3 years after cardiac surgery

Postoperative atrial fibrillation (POAF) after cardiac surgery is an independent predictor of stroke and mortality late after discharge. We aimed to determine the burden and predictors of early (up to 5th postoperative day) and late (after 5th postoperative day) new-onset atrial fibrillation (AF) using implantable loop recorders (ILRs) in patients undergoing open chest cardiac surgery Seventy-nine patients without a history of AF undergoing cardiac surgery underwent peri-operative high-resolution mapping of electrically induced AF and were followed 36 months after surgery using an ILR (Reveal XTTM). Clinical and electrophysiological predictors of late POAF were assessed. POAF occurred in 46 patients (58%), with early POAF detected in 27 (34%) and late POAF in 37 patients (47%). Late POAF episodes were short-lasting (mostly between 2 min and 6 h) and showed a circadian rhythm pattern with a peak of episode initiation during daytime. In POAF patients, electrically induced AF showed more complex propagation patterns than in patients without POAF. Early POAF, right atrial (RA) volume, prolonged PR time, and advanced age were independent predictors of late POAF

Association of ECG characteristics with clinical and echocardiographic outcome to CRT in a non-LBBB patient population

Purpose: Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients. Methods: Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint—echocardiographic reduction of left ventricular end-systolic volume (LVESV)—were evaluated. Results: The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area < 109μVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p < 0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration < 150 ms, PR interval ≥ 230 ms, and in QRS area < 109 μVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 μVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT. Conclusions: In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT

Verapamil versus digoxin and acute versus routine serial cardioversion for the improvement of rhythm control for persistent atrial fibrillation

ObjectivesThe VERDICT (Verapamil Versus Digoxin and Acute Versus Routine Serial Cardioversion Trial) is a prospective, randomized study to investigate whether: 1) acutely repeated serial electrical cardioversions (ECVs) after a relapse of atrial fibrillation (AF); and 2) prevention of intracellular calcium overload by verapamil, decrease intractability of AF.BackgroundRhythm control is desirable in patients suffering from symptomatic AF.MethodsA total of 144 patients with persistent AF were included. Seventy-four (51%) patients were randomized to the acute(within 24 h) and 70 (49%) patients to the routineserial ECVs, and 74 (51%) patients to verapamil and 70 (49%) patients to digoxin for rate control before ECV and continued during follow-up (2 × 2 factorial design). Class III antiarrhythmic drugs were used after a relapse of AF. Follow-up was 18 months.ResultsAt baseline, there were no significant differences between the groups, except for beta-blocker use in the verapamil versus digoxin group (38% vs. 60%, respectively, p = 0.01). At follow-up, no difference in the occurrence of permanent AF between the acute and the routine cardioversion groups was observed (32% [95% confidence intervals (CI)] 22 to 44) vs. 31% [95% CI 21 to 44], respectively, p = NS), and also no difference between the verapamil- and the digoxin-randomized patients (28% [95% CI 19 to 40] vs. 36% [95% CI 25 to 48] respectively, p = NS). Multivariate Cox regression analysis revealed that lone digoxin use was the only significant predictor of failure of rhythm control treatment (hazard ratio 2.2 [95% CI 1.1 to 4.4], p = 0.02).ConclusionsAn acute serial cardioversion strategy does not improve long-term rhythm control in comparison with a routine serial cardioversion strategy. Furthermore, verapamil has no beneficial effect in a serial cardioversion strategy

Targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent atrial fibrillation:Results of the RACE 3 trial

Aims: Atrial fibrillation (AF) is a progressive disease. Targeted therapy of underlying conditions refers to interventions aiming to modify risk factors in order to prevent AF. We hypothesised that targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent AF. Methods and results: We randomized patients with early persistent AF and mild-to-moderate heart failure (HF) to targeted therapy of underlying conditions or conventional therapy. Both groups received causal treatment of AF and HF, and rhythm control therapy. In the intervention group, on top of that, four therapies were started: (i) mineralocorticoid receptor antagonists (MRAs), (ii) statins, (iii) angiotensin converting enzyme inhibitors and/or receptor blockers, and (iv) cardiac rehabilitation including physical activity, dietary restrictions, and counselling. The primary endpoint was sinus rhythm at 1 year during 7 days of Holter monitoring. Of 245 patients, 119 were randomized to targeted and 126 to conventional therapy. The intervention led to a contrast in MRA (101 [85%] vs. 5 [4%] patients, P < 0.001) and statin use (111 [93%] vs. 61 [48%], P < 0.001). Angiotensin converting enzyme inhibitors/angiotensin receptor blockers were not different. Cardiac rehabilitation was completed in 109 (92%) patients. Underlying conditions were more successfully treated in the intervention group. At 1 year, sinus rhythm was present in 89 (75%) patients in the intervention vs. 79 (63%) in the conventional group (odds ratio 1.765, lower limit of 95% confidence interval 1.021, P = 0.042). Conclusions: RACE 3 confirms that targeted therapy of underlying conditions improves sinus rhythm maintenance in patients with persistent AF. Trial Registration number: Clinicaltrials.gov NCT00877643

Effects of a simple cardiac rehabilitation program on improvement of self-reported physical activity in atrial fibrillation - Data from the RACE 3 study

Background and aim: Physical inactivity is associated with an increased prevalence of atrial fibrillation (AF). We aim to evaluate whether cardiac rehabilitation (CR) motivates patients to become and stay physical active, and whether CR affects sinus rhythm maintenance and quality of life (QoL) in patients with persistent AF and moderate heart failure. Methods: In the Routine versus Aggressive risk factor driven upstream rhythm Control for prevention of Early atrial fibrillation in heart failure study patients were randomized to conventional or targeted therapy. Targeted therapy contained next to optimal risk factor management a 3-month CR program, including self-reported physical activity and counseling. Successful physical activity was assessed in the targeted group, defined as activity of moderate intensity >= 150 min/week, or >= 75 min/week of vigorous intensity. AF was assessed at 1 year on 7-days Holter monitoring, QoL using general health, fatigue and AF symptom questionnaires. Results: All 119 patients within the targeted group participated in the CR program, 106 (89%) completed it. At baseline 80 (67%) patients were successfully physical active, 39 (33%) were not. NTproBNP was lower in active patients. During 1-year follow-up physical active patients stayed active: 72 (90%) at 12 weeks, 72 (90%) at 1 year. Inactive patients became active: at 12 weeks 25 (64%) patients and 30 (77%) at 1 year. No benefits were seen on sinus rhythm maintenance and QoL for successful physical active patients. Conclusion: In patients with persistent AF and moderate heart failure participation in CR contributes to improve and to maintain physical activity. (C) 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)