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Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults, yet its underlying pathophysiology remains poorly understood. This study assessed whether circulating biomarker concentrations differ in paroxysmal AF patients during an acute episode compared to sinus rhythm., Methods: The Time of Calamity study is a prospective biomarker study within the RACE V study. Patients underwent venous blood sampling in sinus rhythm at inclusion in RACE V, as well as during a subsequent acute episode of AF for which patients reported to the hospital. Ten biomarkers were analyzed., Results: Thirty-nine patients (mean age 60 ± 9 years, 10 (25 %) women) were enrolled. During an acute AF episode, dickkopf-related protein 3 and insulin-like growth factor binding protein 7 were significantly lower, while N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitive troponin T (hsTnT), growth differentiation factor 15, and interleukin 6 were significantly higher (all p < 0.05)., Conclusions: Biomarker concentrations in paroxysmal AF patients are dynamic and differ between sinus rhythm and acute AF episodes. Notably, NT-proBNP and hsTnT, commonly used in clinical practice, were significantly elevated during an acute AF episode., (Copyright © 2024. Published by Elsevier B.V.)

Because of the increasing use of cardiac implantable electronic devices (CIEDs) with one or more intracardiac electrodes, the rate of lead failure is increasing. Moreover, upgrade of the CIED frequently is indicated for cardiac resynchronization therapy or other reasons. Both these situations require a new intervention, preferably using ipsilateral venous access. However, venous obstruction after CIED insertion occurs in 10%-20% of patients and poses a major obstacle for implantation of additional leads. Possible solutions include lead extraction, contralateral lead insertion, and venoplasty. Preprocedural venoplasty is associated with the lowest short- and long-term risks. Here we describe a step-by-step approach to this technique, which can be introduced and safely performed in most interventional catheterization laboratories., Competing Interests: Disclosures Dr Lipšic has received an institutional educational grant from Abbott Medical Nederland B.V. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Early postoperative atrial fibrillation (POAF) is common after cardiac surgery and is associated with late-POAF recurrences. However, little is known about the burden of POAF and its potential impact on long-term outcomes after cardiac surgery, particularly on the risk for late-POAF recurrences., Objective: The purpose of this study was to establish the distribution of POAF burden and to determine the association between early-POAF burden and late-POAF recurrences during 2.5 years of continuous rhythm monitoring after cardiac surgery in patients with and without preoperative history of atrial fibrillation (AF)., Methods: Patients undergoing cardiac surgery were prospectively enrolled and postoperatively continuously monitored with an implantable loop recorder for 2.5 years. All patients underwent extensive clinical assessment at baseline. During follow-up, all AF episodes were registered, and AF associated metrics, such as burden, were calculated for different time intervals. Early-POAF was defined as AF within first 90 postoperative days and late-POAF as AF after this interval., Results: A total of 98 consecutive patients were included. POAF burden during the early postoperative phase was significantly higher compared to the late postoperative phase (P <.001). The longest individual POAF episode was strongly associated with increased POAF burden after adjusting for age, sex, and AF history (standardized Beta: 0.91, P <.001). Also, early-POAF burden was associated with late-POAF (re)occurrence after adjusting for age, sex, AF history (adjusted hazard ratio 1.93, 95% confidence interval 1.42-2.62, P <.001)., Conclusion: POAF burden was significantly associated with the longest individual POAF episode duration. Additionally, greater early-POAF burden was associated with increased late-POAF incidence, highlighting its potential in estimating the risk for long-term POAF recurrences., Competing Interests: Disclosures Dr Schotten received consultancy fees or honoraria from Università della Svizzera Italiana (USI, Switzerland), Roche Diagnostics (Switzerland), EP Solutions Inc. (Switzerland), Johnson & Johnson Medical Limited (United Kingdom), and Bayer Healthcare (Germany); and is co-founder and shareholder of YourRhythmics BV, a spin-off company of the University Maastricht. Dr Maesen is a consultant for AtriCure and Medtronic. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The effect of haemodynamic monitoring of pulmonary artery pressure has predominantly been studied in the USA. There is a clear need for randomised trial data from patients treated with contemporary guideline-directed-medical-therapy with long-term follow-up in a different health-care system., Methods: MONITOR-HF was an open-label, randomised trial, done in 25 centres in the Netherlands. Eligible patients had chronic heart failure of New York Heart Association class III and a previous heart failure hospitalisation, irrespective of ejection fraction. Patients were randomly assigned (1:1) to haemodynamic monitoring (CardioMEMS-HF system, Abbott Laboratories, Abbott Park, IL, USA) or standard care. All patients were scheduled to be seen by their clinician at 3 months and 6 months, and every 6 months thereafter, up to 48 months. The primary endpoint was the mean difference in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 12 months. All analyses were by intention-to-treat. This trial was prospectively registered under the clinical trial registration number NTR7673 (NL7430) on the International Clinical Trials Registry Platform., Findings: Between April 1, 2019, and Jan 14, 2022, we randomly assigned 348 patients to either the CardioMEMS-HF group (n=176 [51%]) or the control group (n=172 [49%]). The median age was 69 years (IQR 61-75) and median ejection fraction was 30% (23-40). The difference in mean change in KCCQ overall summary score at 12 months was 7·13 (95% CI 1·51-12·75; p=0·013) between groups (+7·05 in the CardioMEMS group, p=0·0014, and -0·08 in the standard care group, p=0·97). In the responder analysis, the odds ratio (OR) of an improvement of at least 5 points in KCCQ overall summary score was OR 1·69 (95% CI 1·01-2·83; p=0·046) and the OR of a deterioration of at least 5 points was 0·45 (0·26-0·77; p=0·0035) in the CardioMEMS-HF group compared with in the standard care group. The freedom of device-related or system-related complications and sensor failure were 97·7% and 98·8%, respectively., Interpretation: Haemodynamic monitoring substantially improved quality of life and reduced heart failure hospitalisations in patients with moderate-to-severe heart failure treated according to contemporary guidelines. These findings contribute to the aggregate evidence for this technology and might have implications for guideline recommendations and implementation of remote pulmonary artery pressure monitoring., Funding: The Dutch Ministry of Health, Health Care Institute (Zorginstituut), and Abbott Laboratories., Competing Interests: Declaration of interests JJB received an independent research grant from Abbott for investigator-initiated studies to the hospital and reports speaker engagement or advisory board fees from Astra Zeneca, Abbott, Boehringer Ingelheim, Bayer, Daiichi Sankyo, Novartis, and Vifor. CAdF received consulting or speaker fees from Astra Zeneca, Abbott, Boehringer Ingelheim, Novartis, Pfizer, Bristol Myers Squibb, Philips, and Servier. CJWB served on advisory boards, or had speaker engagements with Abbott, AstraZeneca, Boehringer Ingelheim, and Novartis. HPB-LR reports unrestricted research grants from Vifor, Novartis, and Roche Diagnostics, and reports consultancy fees and payments for lectures from Vifor, Novartis, Boehringer Ingelheim, AstraZeneca, and Roche Diagnostic. RAdB has received research grants or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals, Ionis Pharmaceuticals, Novo Nordisk, and Roche; and has had speaker engagements with Abbott, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, and Roche. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The assessment of symptom-rhythm correlation (SRC) in patients with persistent atrial fibrillation (AF) is challenging. Therefore, we performed a novel mobile app-based approach to assess SRC in persistent AF., Methods: Consecutive persistent AF patients planned for electrical cardioversion (ECV) used a mobile app to record a 60-s photoplethysmogram (PPG) and report symptoms once daily and in case of symptoms for four weeks prior and three weeks after ECV. Within each patient, SRC was quantified by the SRC-index defined as the sum of symptomatic AF recordings and asymptomatic non-AF recordings divided by the sum of all recordings., Results: Of 88 patients (33% women, age 68 ± 9 years) included, 78% reported any symptoms during recordings. The overall SRC-index was 0.61 (0.44-0.79). The study population was divided into SRC-index tertiles: low (<0.47), medium (0.47-0.73) and high (≥0.73). Patients within the low (vs high) SRC-index tertile had more often heart failure and diabetes mellitus (both 24.1% vs 6.9%). Extrasystoles occurred in 19% of all symptomatic non-AF PPG recordings. Within each patient, PPG recordings with the highest (vs lowest) tertile of pulse rates conferred an increased risk for symptomatic AF recordings (odds ratio [OR] 1.26, 95% coincidence interval [CI] 1.04-1.52) and symptomatic non-AF recordings (OR 2.93, 95% CI 2.16-3.97). Pulse variability was not associated with reported symptoms., Conclusions: In patients with persistent AF, SRC is relatively low. Pulse rate is the main determinant of reported symptoms. Further studies are required to verify whether integrating mobile app-based SRC assessment in current workflows can improve AF management., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: To identify the association between comorbidities and left atrial (LA) and right atrial (RA) function in patients with paroxysmal atrial fibrillation (AF)., Methods: This is a cross-sectional study. Speckle-tracking echocardiography was performed in 344 patients with paroxysmal AF at baseline, and available in 298 patients after 1-year follow-up. The number of comorbidities (hypertension, diabetes mellitus, coronary artery disease, body mass index > 25 kg/m 2 , age > 65 years, moderate to severe mitral valve regurgitation and kidney dysfunction (estimated glomerular filtration rate < 60 ml/min/1.73 m 2 )) was determined and the association with atrial strain was tested., Results: Mean age of the patients was 58 (SD 12) years and 137 patients were women (40%). Patients with a higher number of comorbidities had larger LA volumes (p for trend <0.001), and had a decrease in all strain phases from the LA and RA, except for the RA contraction phase (p for trend 0.47). A higher number of comorbidities was associated with LA reservoir and conduit strain decrease independently of LA volume (p < 0.001, p < 0.001 respectively). Patients with 1-2 comorbidities, but not patients with 3 or more comorbidities, showed a further progression of impaired LA and RA function in almost all atrial strain phases at 14 [13-17] months follow-up., Conclusions: In patients with paroxysmal AF, individual and combined comorbidities are related to lower LA and RA strain. In patients with few comorbidities, impairment in atrial function progresses during one year of follow-up. Whether comorbidity management prevents or reverses decrease in atrial function warrants further study., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Obesity is associated with cardiovascular (CV) risk factors and diseases. Because bariatric surgery is increasingly performed in relatively elderly patients, a risk for pre- and postoperative CV complications exists., Objectives: We aimed to assess the value of plasma N-terminal-probrain natriuretic peptide (NT-proBNP) as a CV screening tool., Setting: High-volume bariatric center., Methods: Between June 2019 and January 2020, all consecutive bariatric patients 50 years and older underwent preoperative NT-proBNP assessment in this cohort study to screen for CV disease. Patients with elevated NT-proBNP (≥125 pg/mL) were referred for further cardiac evaluation, including electrocardiography and echocardiography., Results: We included 310 consecutive patients (median age, 56 years; 79% female; body mass index = 43±6.5 kg/m 2 ). A history of CV disease was present in 21% of patients, mainly atrial fibrillation (7%) and coronary artery disease (10%). A total of 72 patients (23%) had elevated NT-proBNP levels, and 67 of them underwent further cardiac workup. Of these 67 patients, electrocardiography (ECG) showed atrial fibrillation in 7 patients (10%). On echocardiography, 3 patients had left ventricular ejection fraction (LVEF) <40%, 9 patients had LVEF 40%-49%, and 13 patients had LVEF ≥50% with structural and/or functional remodeling. In 2 patients, elevated NT-proBNP prompted workup leading to a diagnosis of coronary artery disease and consequent percutaneous coronary intervention in 1 patient., Conclusions: Elevated NT-proBNP levels are present in 23% of patients 50 years and older undergoing bariatric surgery. In 37% of them, there was echocardiographic evidence for structural and/or functional remodeling. Further studies are needed to assess if these preliminary results warrant routine application of NT-proBNP to identify patients at risk for CV complications after bariatric surgery., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objectives: This study examined associations between epicardial adipose tissue (EAT), invasive hemodynamics, and exercise capacity in patients with heart failure with preserved ejection fraction (HFpEF)., Background: EAT is increased in patients with HFpEF and may play a role in the pathophysiology of this disorder., Methods: Patients with heart failure and a left ventricular ejection fraction >45% who underwent right and left heart catheterization with simultaneous echocardiography were included. Pulmonary capillary wedge pressure (PCWP), left ventricular end-diastolic pressure (LVEDP), right ventricular end-diastolic pressure (RVEDP), and pulmonary vascular resistance (PVR) were invasively measured. Obesity was defined as body mass index (BMI) ≥30 kg/m 2 . EAT thickness alongside the right ventricle was measured on echocardiographic long- and short-axis views. Cardiopulmonary exercise testing was performed to obtain maximal oxygen uptake (VO 2 -max)., Results: This study examined 75 patients, mean age 74 ± 9 years; 68% were women, mean BMI was 29 ± 6 kg/m 2 , and 36% were obese. Higher BMI was strongly associated with increased EAT (r = 0.74; p < 0.001). Increased EAT was associated with higher RVEDP, independent of PVR (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.02 to 1.34; p = 0.03), but not independent of obesity (p = 0.10). Increased EAT and higher RVEDP were both associated with lower VO 2 -max (r = -0.43; p < 0.001 and r = -0.43; p = 0.001, respectively). Increased EAT remained associated with lower VO 2 -max after adjustment for PVR (OR: 0.64; 95% CI: 0.49 to 0.84; p = 0.002) and obesity (OR: 0.69; 95% CI: 0.53 to 0.92; p = 0.01). EAT thickness was not associated with left-sided filling pressures (i.e., PCWP and LVEDP)., Conclusions: In HFpEF, obesity and increased EAT were associated with higher right-sided filling pressures and with reduced exercise capacity., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is common in chronic heart failure (HF) patients and influences the choice and effects of drug and device therapy. In this large real-world HF registry, we studied whether the presence of AF affects the prescription of guideline-recommended HF therapy., Methods: We analyzed 8253 patients with chronic HF with reduced ejection fraction (HFrEF) from 34 Dutch outpatient clinics included in the period between 2013 and 2016 treated according to the 2012 ESC guidelines., Results: 2109 (25.6%) of these patients were in AF (mean age 76.8 ± 9.2 years, 65.0% were men) and 6.144 (74.4%) had no AF (mean age 70.7 ± 12.2 years, 63.6% were men). Patients with AF more often received beta-blockers (81.7% vs. 79.7%, p = 0.04), MRAs (57.1% vs. 51.7%, p < 0.01), diuretics (89.7% vs. 80.6%, p < 0.01) and digoxin (40.1% vs. 9.3%, p < 0.01) compared to patients without AF, whereas they less often receive renin-angiotensin-system (RAS)-inhibitors (76.1% vs. 83.1%, p < 0.01). The number of patients who received beta-blockers, RAS-inhibitor and MRA at ≥50% of the recommended target dose was comparable between those with and without AF (16.6% vs. 15.2%, p = 0.07)., Conclusion: In this large cohort of chronic HFrEF patients, the prevalence of AF was high and we observed significant differences in prescription of both guideline-recommended HF between patients with and without AF., Competing Interests: Declaration of competing interest All authors report no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The purpose of this study was to compare the effectiveness of bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF)., Background: Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta 1 -adrenergic receptor (ADRB1) Arg389Arg genotype., Methods: A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) <0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype were randomized 1:1 to receive bucindolol or metoprolol therapy and were up-titrated to target doses. The primary endpoint of AF or atrial flutter (AFL) or all-cause mortality (ACM) was evaluated by electrocardiogram (ECG) during a 24-week period., Results: The hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were <12 years prior to randomization, in which AF onset did not precede HF by more than 2 years (n = 196), the HR was 0.54 (95% CI: 0.33 to 0.87; p = 0.011)., Conclusions: Pharmacogenetically guided bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials., (Copyright © 2019. Published by Elsevier Inc.)

Background: The LifeLines Cohort Study is a large three-generation prospective study and Biobank. Recruitment and data collection started in 2006 and follow-up is planned for 30years. The central aim of LifeLines is to understand healthy ageing in the 21st century. Here, the study design, methods, baseline and major cardiovascular phenotypes of the LifeLines Cohort Study are presented., Methods and Results: Baseline cardiovascular phenotypes were defined in 9700 juvenile (8-18years) and 152,180 adult (≥18years) participants. Cardiovascular disease (CVD) was defined using ICD-10 criteria. At least one cardiovascular risk factor was present in 73% of the adult participants. The prevalence, adjusted for the Dutch population, was determined for risk factors (hypertension (33%), hypercholesterolemia (19%), diabetes (4%), overweight (56%), and current smoking (19%)) and CVD (myocardial infarction (1.8%), heart failure (1.0%), and atrial fibrillation (1.3%)). Overall CVD prevalence increased with age from 9% in participants<65years to 28% in participants≥65years. Of the participants with hypertension, hypercholesterolemia and diabetes, respectively 75%, 96% and 41% did not receive preventive pharmacotherapy., Conclusions: The contemporary LifeLines Cohort Study provides researchers with unique and novel opportunities to study environmental, phenotypic, and genetic risk factors for CVD and is expected to improve our knowledge on healthy ageing. In this contemporary Western cohort we identified a remarkable high percentage of untreated CVD risk factors suggesting that not all opportunities to reduce the CVD burden are utilised., (Copyright © 2016 Swiss Tropical and Public Health Institute. Published by Elsevier Ireland Ltd.. All rights reserved.)

Objectives: This study sought to study the association of atrial fibrillation (AF) with exercise capacity, left ventricular filling pressure, natriuretic peptides, and left atrial size in heart failure with preserved ejection fraction (HFpEF)., Background: The diagnosis of HFpEF in patients with AF remains a challenge because both contribute to impaired exercise capacity, and increased natriuretic peptides and left atrial volume., Methods: We studied 94 patients with symptomatic heart failure and left ventricular ejection fractions ≥45% using treadmill cardiopulmonary exercise testing and right- and/or left-sided cardiac catheterization with simultaneous echocardiography., Results: During catheterization, 62 patients were in sinus rhythm, and 32 patients had AF. There were no significant differences in age, sex, body size, comorbidities, or medications between groups; however, patients with AF had lower peak oxygen consumption (VO 2 ) compared with those with sinus rhythm (10.8 ± 3.1 ml/min/kg vs. 13.5 ± 3.8 ml/min/kg; p = 0.002). Median (25th to 75th percentile) N-terminal pro-B-type natriuretic peptide (NT-proBNP) was higher in AF versus sinus rhythm (1,689; 851 to 2,637 pg/ml vs. 490; 272 to 1,019 pg/ml; p < 0.0001). Left atrial volume index (LAVI) was higher in AF than sinus rhythm (57.8 ± 17.0 ml/m 2 vs. 42.5 ± 15.1 ml/m 2 ; p = 0.001). Invasive hemodynamics showed higher mean pulmonary capillary wedge pressure (PCWP) (19.9 ± 3.7 vs. 15.2 ± 6.8) in AF versus sinus rhythm (all p < 0.001), with a trend toward higher left ventricular end-diastolic pressure (17.7 ± 3.0 mm Hg vs. 15.7 ± 6.9 mm Hg; p = 0.06). After adjusting for clinical covariates and mean PCWP, AF remained associated with reduced peak VO 2 increased log NT-proBNP, and enlarged LAVI (all p ≤0.005)., Conclusions: AF is independently associated with greater exertional intolerance, natriuretic peptide elevation, and left atrial remodeling in HFpEF. These data support the application of different thresholds of NT-proBNP and LAVI for the diagnosis of HFpEF in the presence of AF versus the absence of AF., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Control of the heart rate (rate control) is central to atrial fibrillation management, even for patients who ultimately require control of the rhythm. We review heart rate control in patients with atrial fibrillation, including the rationale for the intervention, patient selection, and the treatments available. The choice of rate control depends on the symptoms and clinical characteristics of the patient, but for all patients with atrial fibrillation, rate control is part of the management. Choice of drugs is patient-dependent. β blockers, alone or in combination with digoxin, or non-dihydropyridine calcium-channel blockers (not in heart failure) effectively lower the heart rate. Digoxin is least effective, but a reasonable choice for physically inactive patients aged 80 years or older, in whom other treatments are ineffective or are contraindicated, and as an additional drug to other rate-controlling drugs, especially in heart failure when instituted cautiously. Atrioventricular node ablation with pacemaker insertion for rate control should be used as an approach of last resort but is also an option early in the management of patients with atrial fibrillation treated with cardiac resynchronisation therapy. However, catheter ablation of atrial fibrillation should be considered before atrioventricular node ablation. Although rate control is a top priority and one of the first management issues for all patients with atrial fibrillation, many issues remain., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: The Atrial Fibrillation Follow-up Investigation of Rhythm Management trial showed that digoxin was associated with increased mortality in patients with atrial fibrillation., Objectives: To assess the association of digoxin with cardiovascular (CV) morbidity and mortality in patients with permanent atrial fibrillation enrolled in the Dutch Rate Control Efficacy in Permanent AF: A Comparison Between Lenient Versus Strict Rate Control II trial as well as to assess the role of digoxin to achieve heart rate targets., Methods: The primary outcome was a composite of CV morbidity and mortality. Secondary outcomes included CV hospitalization and all-cause mortality or heart failure (HF) hospitalization. Of the 614 patients, 608 (99%) completed the dose-adjustment phase. Outcome events were analyzed from the end of the dose-adjustment phase until the end of follow-up. The median follow-up period was 2.9 years (interquartile range 2.7-3.0 years)., Results: In total, 284 patients (46.7%) used digoxin after the dose-adjustment phase (median dosage 0.250 mg; interquartile range 0.0625-0.750 mg). These patients were more often women, previously admitted for HF, had an increased left ventricular end-systolic diameter, and more often randomized to strict rate control. By using Cox proportional hazards regression analysis, the use of digoxin was not associated with an increased risk for the primary and secondary outcomes. For the primary outcome, the 3-year estimated cumulative incidence was 12.9% vs 13.4% in the digoxin group vs the no-digoxin group (unadjusted hazard ratio [HR] 0.97; 95% confidence interval [CI] 0.62-1.52). Incidence was 19.4% vs. 19.5% for CV hospitalization (unadjusted HR 1.00; 95% CI 0.69-1.45) and 6.6% vs. 9.9% for all-cause mortality or HF hospitalization (unadjusted HR 0.62; 95% CI 0.34-1.13) in the digoxin group vs the no-digoxin group., Conclusion: The use of digoxin was not associated with increased morbidity and mortality., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Symptoms are a major driver for patients with atrial fibrillation (AF) to seek medical attention and are important to titrate AF therapies. However, a large proportion of patients with AF are asymptomatic., Objective: To investigate the clinical profile and prognosis of patients with asymptomatic recurrent persistent AF in the RAte Control versus Electrical cardioversion for persistent atrial fibrillation study., Methods: Patients with asymptomatic AF (n = 157 [30%]) were compared with patients with symptomatic AF (n = 365 [70%]). The primary end point was a composite of cardiovascular morbidity and mortality., Results: Patients with asymptomatic AF were younger and more often men than were patients with symptomatic AF. Cardiac diseases were less common. Quality of life (the Medical Outcomes Study Short-form health survey questionnaire) was better in patients with asymptomatic AF and comparable to healthy controls. At baseline and during follow-up, there were no differences in rate control, antiarrhythmic, or anticoagulant drugs; cardioversions; and time in sinus rhythm. After a follow-up of 2.3 ± 0.6 years, the primary end point occurred in 21 (13%) patients with asymptomatic AF and 83 (23%) patients with symptomatic AF. After adjusting for relevant covariates, asymptomatic AF was associated with a lower risk of the primary end point (hazard ratio 0.51; 95% confidence interval 0.29-0.92; P = .024). This difference was driven by significantly less heart failure hospitalizations (0 vs 21 [6%]) and severe effects of antiarrhythmic drugs or digoxin (1 [0.6%] vs 13 [4%]). Importantly, no difference in the occurrence of thromboembolic complications was observed., Conclusion: Patients with asymptomatic AF were more often men and had less cardiac disease. During follow-up, in patients with asymptomatic AF, heart failure hospitalizations and severe adverse effects of antiarrhythmic and rate control drugs occurred significantly less frequently., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Genome-wide association studies (GWAS) have identified common genetic variants that predispose to atrial fibrillation (AF). It is unclear whether rare and low-frequency variants in genes implicated by such GWAS confer additional risk of AF., Objective: To study the association of genetic variants with AF at GWAS top loci., Methods: In the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Targeted Sequencing Study, we selected and sequenced 77 target gene regions from GWAS loci of complex diseases or traits, including 4 genes hypothesized to be related to AF (PRRX1, CAV1, CAV2, and ZFHX3). Sequencing was performed in participants with (n = 948) and without (n = 3330) AF from the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Massachusetts General Hospital., Results: One common variant (rs11265611; P = 1.70 × 10(-6)) intronic to IL6R (interleukin-6 receptor gene) was significantly associated with AF after Bonferroni correction (odds ratio 0.70; 95% confidence interval 0.58-0.85). The variant was not genotyped or imputed by prior GWAS, but it is in linkage disequilibrium (r(2) = .69) with the single-nucleotide polymorphism, with the strongest association with AF so far at this locus (rs4845625). In the rare variant joint analysis, damaging variants within the PRRX1 region showed significant association with AF after Bonferroni correction (P = .01)., Conclusions: We identified 1 common single-nucleotide polymorphism and 1 gene region that were significantly associated with AF. Future sequencing efforts with larger sample sizes and more comprehensive genome coverage are anticipated to identify additional AF-related variants., (© 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.)

Objectives: Traditional clinical risk factors are associated with inflammation cross-sectionally, but associations of longitudinal variation in inflammatory biomarkers with corresponding changes in clinical risk factors are incompletely described. We sought to analyze clinical factors associated with change in inflammation in the community., Methods: We studied 3013 Framingham Offspring (n = 2735) and Omni Cohort (n = 278) participants (mean age 59 years, 55% women, 9% ethnic/racial minority) who attended two consecutive examination cycles (mean 6.7 years apart). We selected ten inflammatory biomarkers representing distinctive biological functions: C-reactive protein (CRP), intercellular adhesion molecule-1, interleukin-6, isoprostanes, lipoprotein-associated phospholipase-2 (Lp-PLA2) activity, Lp-PLA2-mass, monocyte chemoattractant protein-1, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II (TNFRII). We constructed multivariable-adjusted regression models to assess the relations of baseline, follow-up and change in clinical risk factors with change in biomarker concentrations over time., Results: Baseline, follow-up and change in clinical risk factors explain a moderate amount of the variation in biomarker concentrations across 2 consecutive examinations (ranging from r(2) = 0.28 [TNFRII] up to 0.52 [Lp-PLA2-mass]). In multivariable models, increasing body-mass index, smoking initiation, worsening lipid profile, and increasing waist size were associated with increasing concentrations of several biomarkers. Conversely, hypercholesterolemia therapy and hormone replacement cessation were associated with decreasing concentrations of biomarkers such as CRP, Lp-PLA2-mass and activity., Conclusion: Cardiovascular risk factors have different patterns of association with longitudinal change in inflammatory biomarkers and explain modest amounts of variability in biomarker concentrations. Nevertheless, a substantial proportion of longitudinal change in inflammatory markers is not explained by traditional risk factors., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The purpose of this study was to analyze the effect of beta blockade on outcome in patients with heart failure (HF) and atrial fibrillation (AF)., Background: Beta-blockers are widely used in patients with HF and AF. Recommendation in current HF guidelines, however, is based on populations in which the most patients had sinus rhythm. Whether beta-blockers are as useful in AF is uncertain., Methods: Studies were included that investigated the effect of placebo-controlled, randomized beta-blocker therapy in patients with AF at baseline and HF with reduced systolic left ventricular ejection fraction (LVEF) <40%., Results: We identified 4 studies, which enrolled 8,680 patients with HF, and 1,677 of them had AF (19%; mean 68 years of age; 30% women); there were 842 patients treated with beta-blocker, and 835 with placebo. In AF patients, beta-blockade did not reduce mortality (odds ratio [OR]: 0.86 [95% confidence interval (CI): 0.66 to 1.13]; p = 0.28), while in sinus rhythm patients, there was a significant reduction (OR: 0.63 [95% CI: 0.54 to 0.73]; p < 0.0001). Interaction analysis showed significant interaction of the effects of beta-blocker therapy in AF versus that in sinus rhythm (p = 0.048). By meta-regression analysis, we did not find confounding by all relevant covariates. Beta-blocker therapy was not associated with a reduction in HF hospitalizations in AF (OR: 1.11 [95% CI: 0.85 to 1.47]; p = 0.44), in contrast to sinus rhythm (OR: 0.58 [95% CI: 0.49 to 0.68]; p < 0.0001). There was a significant interaction of the effects of beta-blocker therapy in AF versus that in sinus rhythm (p < 0.001)., Conclusions: Our findings suggest that the effect of beta-blockers on outcome in HF patients with reduced systolic LVEF who have AF is less than in those who have sinus rhythm., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation is common in chronic heart failure. Long-term restoration of sinus rhythm is generally unsuccessful. It may be speculated that higher heart rates are unfavorable, since this may lead to tachycardiomyopathy, but there are no data which have examined this., Methods and Results: Seventy-seven patients with atrial fibrillation and advanced chronic heart failure, age 70 +/- 7 years, left-ventricular ejection fraction 0.23 +/- 0.08, 61% with ischemic etiology were included. Patients were dichotomized according to the median heart rate (80 bpm) at inclusion (39 patients with "low" heart rate and 38 patients with "high" heart rate). At baseline, both patient groups were remarkably comparable. After a mean follow-up of 3.3 +/- 0.9 years, mortality was comparable (62% versus 55%, p = non-significant). An independent relation was found between lower heart rate and survival, in addition to absence of hypertension, digoxin use, and higher N-ANP, dopamine, and renin levels., Conclusion: In the present analysis, patients with atrial fibrillation and advanced chronic heart failure with higher heart rates are comparable to those with lower heart rates. Not higher heart rates at baseline but, on the contrary, lower heart rates seem associated with a worse outcome.

Objectives: The purpose of this study was to evaluate left ventricular function and atrial and ventricular diameters in patients with persistent atrial fibrillation (AF) treated with rate or rhythm control., Background: Restoration of sinus rhythm in patients with persistent AF may improve left ventricular function and reduce atrial dimensions. Adequate rate control in AF may preserve ventricular function., Methods: In 335 patients included in the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study, echocardiography was performed at baseline and 1- and 2-year follow-up. Echocardiography was compared between patients randomized to rate control (n = 160) and rhythm control (n = 175). In the rhythm control group, echocardiography was compared between patients with AF versus sinus rhythm at study end. Multivariate analysis was performed to determine parameters related to improvement of left ventricular function and increase of atrial diameters., Results: Fractional shortening improved significantly under rate and rhythm control (31 +/- 10% at baseline to 33 +/- 9% at 2 years, and from 30 +/- 10% to 34 +/- 9%; both P < .05, respectively). Under rate control, left and right atrial size increased significantly compared to baseline. Under rhythm control, only left atrial size increased. Multivariate analysis revealed that only sinus rhythm at study end was associated with an increase of fractional shortening. AF at study end, hypertension, and no use of angiotensin-converting enzyme inhibitors were independently associated with increase in atrial size., Conclusions: Routine rate control prevents deterioration of left ventricular function. Maintenance of sinus rhythm is associated with improvement of left ventricular function and reduction of atrial sizes.