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Objective: Atrial fibrillation (AF) is associated with adverse events including conduction disturbances, ventricular arrhythmias and sudden death. The aim of this study was to examine brady- and tachyarrhythmias using continuous rhythm monitoring in patients with paroxysmal self-terminating AF (PAF)., Methods: In this multicentre observational substudy to the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V), we included 392 patients with PAF and at least 2 years of continuous rhythm monitoring. All patients received an implantable loop recorder, and all detected episodes of tachycardia ≥182 beats per minute (BPM), bradycardia ≤30 BPM or pauses ≥5 s were adjudicated by three physicians., Results: Over 1272 patient-years of continuous rhythm monitoring, we adjudicated 1940 episodes in 175 patients (45%): 106 (27%) patients experienced rapid AF or atrial flutter (AFL), pauses ≥5 s or bradycardias ≤30 BPM occurred in 47 (12%) patients and in 22 (6%) patients, we observed both episode types. No sustained ventricular tachycardias occurred. In the multivariable analysis, age >70 years (HR 2.3, 95% CI 1.4 to 3.9), longer PR interval (HR 1.9, 1.1-3.1), CHA 2 DS 2 -VASc score ≥2 (HR 2.2, 1.1-4.5) and treatment with verapamil or diltiazem (HR 0.4, 0.2-1.0) were significantly associated with bradyarrhythmia episodes. Age >70 years was associated with lower rates of tachyarrhythmias., Conclusions: In a cohort exclusive to patients with PAF, almost half experienced severe bradyarrhythmias or AF/AFL with rapid ventricular rates. Our data highlight a higher than anticipated bradyarrhythmia risk in PAF., Trial Registration Number: NCT02726698., Competing Interests: Competing interests: MHJPF received speakers’ honorarium from Medtronic outside submitted work. RGT reports grants from Medtronic and Abbott, and personal fees from Boehringer Ingelheim, Bayer and Pfizer/Bristol Myers Squibb all outside submitted work. RGT is coinventor of the MyDiagnostick, not receiving royalties for the past 5 years. MDM is a Medtronic employee and WP Coordinator in the H2020 ITN My-Atria (No: 766082). IVG and AHM serve on the editorial board of BMJ Heart. The remaining authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Atrial fibrillation (AF) often starts as a paroxysmal self-terminating arrhythmia. Limited information is available on AF patterns and episode duration of paroxysmal AF. In paroxysmal AF patients, we longitudinally studied the temporal AF patterns, the association with clinical characteristics, and prevalence of AF progression., Methods and Results: In this interim analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) registry, 202 patients with paroxysmal AF were followed with continuous rhythm monitoring (implantable loop recorder or pacemaker) for 6 months. Mean age was 64 ± 9 years, 42% were women. Atrial fibrillation history was 2.1 (0.5-4.4) years, CHA2DS2-VASc 1.9 ± 1.3, 101 (50%) had hypertension, 69 (34%) heart failure. One-third had no AF during follow-up. Patients with long episodes (>12 hours) were often men with more comorbidities (heart failure, coronary artery disease, higher left ventricular mass). Patients with higher AF burden (>2.5%) were older with more comorbidities (worse renal function, higher calcium score, thicker intima media thickness). In 179 (89%) patients, 1-year rhythm follow-up was available. On a quarterly basis, average daily AF burden increased from 3.2% to 3.8%, 5.2%, and 6.1%. Compared to the first 6 months, 111 (62%) patients remained stable during the second 6 months, 39 (22%) showed progression to longer AF episodes, 8 (3%) developed persistent AF, and 29 (16%) patients showed AF regression., Conclusions: In paroxysmal AF, temporal patterns differ suggesting that paroxysmal AF is not one entity. Atrial fibrillation burden is low and determined by number of comorbidities. Atrial fibrillation progression occurred in a substantial number., Trial Registration Number: Clinicaltrials.gov identifier NCT02726698., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are very common conditions, particularly in the elderly. However, the mechanisms underlying the two disorders, including their intricate interaction have not been fully resolved. Here, our aim is to review the evidence on the role of the two types of senile amyloidosis in this connection. Two types of senile amyloidosis can be identified: wild-type transthyretin (TTR)-derived amyloidosis (ATTRwt) and isolated atrial amyloidosis (IAA). ATTRwt is an underlying condition that is being increasingly recognized in patients with HFpEF and often accompanied by AF. IAA is an established cause of AF, adding to the mechanism problem. New diagnostic and therapeutic possibilities have emerged that may facilitate clinical management of (senile) amyloidosis, which in turn may have implications for the management of HFpEF and AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: Atrial fibrillation (AF) produces a hypercoagulable state. Stimulation of protease-activated receptors by coagulation factors provokes pro-fibrotic, pro-hypertrophic, and pro-inflammatory responses in a variety of tissues. We studied the effects of thrombin on atrial fibroblasts and tested the hypothesis that hypercoagulability contributes to the development of a substrate for AF., Methods and Results: In isolated rat atrial fibroblasts, thrombin enhanced the phosphorylation of the pro-fibrotic signalling molecules Akt and Erk and increased the expression of transforming growth factor β1 (2.7-fold) and the pro-inflammatory factor monocyte chemoattractant protein-1 (6.1-fold). Thrombin also increased the incorporation of 3 H-proline, suggesting enhanced collagen synthesis by fibroblasts (2.5-fold). All effects could be attenuated by the thrombin inhibitor dabigatran. In transgenic mice with a pro-coagulant phenotype (TM pro/pro ), the inducibility of AF episodes lasting >1 s was higher (7 out of 12 vs. 1 out of 10 in wild type) and duration of AF episodes was longer compared with wild type mice (maximum episode duration 42.8 ± 68.4 vs. 0.23 ± 0.39 s). In six goats with persistent AF treated with nadroparin, targeting Factor Xa-mediated thrombin generation, the complexity of the AF substrate was less pronounced than in control animals (LA maximal activation time differences 23.3 ± 3.1 ms in control vs. 15.7 ± 2.1 ms in nadroparin, P < 0.05). In the treated animals, AF-induced α-smooth muscle actin expression was lower and endomysial fibrosis was less pronounced., Conclusion: The hypercoagulable state during AF causes pro-fibrotic and pro-inflammatory responses in adult atrial fibroblasts. Hypercoagulability promotes the development of a substrate for AF in transgenic mice and in goats with persistent AF. In AF goats, nadroparin attenuates atrial fibrosis and the complexity of the AF substrate. Inhibition of coagulation may not only prevent strokes but also inhibit the development of a substrate for AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

The landmark trials on cardiac resynchronization therapy (CRT) have focused on patients with sinus rhythm at inclusion. Little data are available on the efficacy of CRT in patients with atrial fibrillation (AF), while AF has a high prevalence (20-40%) among patients receiving CRT. This review focuses on the detrimental effect of AF on CRT response and discusses management of patients with AF during CRT. Uncertainty remains as to which thresholds of AF burden can lead to a reduced response to CRT and every effort should be made in trying to assess and guarantee successful biventricular pacing in patients with AF., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: To study the prognostic effect of atrial reverse remodelling on outcome of cardiac resynchronization therapy (CRT)., Methods and Results: Patients receiving a CRT device in the University Medical Centre Groningen were included. Atrial reverse remodelling was defined as a ≥10% reduction in left atrial volume index at 6-month follow-up. Success of CRT was defined as ventricular reverse remodelling with a reduction in left ventricular end-systolic volume of ≥15% at 6-month follow-up. Primary endpoint was all-cause mortality or heart failure hospitalizations. A total of 365 patients (mean age 65.1 ± 11.0 years, 73% men) were included; among them, 221 (61%) were in sinus rhythm and had no prior atrial fibrillation (AF), and 144 patients (39%) had a history of AF. During a mean follow up of 2.0 ± 1.0 years, 49 patients died. Cox regression analysis revealed that patients with no atrial and no ventricular reverse remodelling had the worst outcome (hazard ratio 3.1, 95% confidence interval 1.4-7.1, P = 0.006). Outcome in patients with only atrial reverse remodelling was comparable with outcome in patients with both atrial and ventricular reverse remodelling (hazard ratio 2.0, 95% confidence interval 0.7-5.6, P = 0.21)., Conclusion: Patients without atrial and ventricular reverse remodelling have the worst outcome. Patients with only atrial reverse remodelling have improved left ventricular diastolic filling during follow-up and demonstrate a comparable outcome with patients with both atrial and ventricular reverse remodelling. Assessment of atrial reverse remodelling may provide additional prognostic information in determining CRT outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

The landmark trials on cardiac resynchronization therapy (CRT) have focused on patients with sinus rhythm at inclusion. Little data are available on the efficacy of CRT in patients with atrial fibrillation (AF), while AF has a high prevalence (20-40%) among patients receiving CRT. This review focuses on the detrimental effect of AF on CRT response and discusses management of patients with AF during CRT. Uncertainty remains as to which thresholds of AF burden can lead to a reduced response to CRT and every effort should be made in trying to assess and guarantee successful biventricular pacing in patients with AF., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is often preceded by underlying cardiac diseases causing ventricular pressure overload., Objective: It was our aim to investigate the progression of atrial remodeling in a small animal model of ventricular pressure overload and its association with induction of AF., Methods: Male mice were subjected to transverse aortic constriction (TAC) or sham operation. After four or eight weeks, echocardiographic measurements and hemodynamic measurements were made and AF induction was tested. The hearts were either fixed in formalin or ventricles and atria were separated, weighed and snap-frozen for RNA analysis., Results: Four weeks of pressure overload induced ventricular hypertrophy and minor changes in the atria. After eight weeks a significant reduction in left ventricular function occurred, associated with significant atrial remodeling including increased atrial weight, a trend towards an increased left atrial cell diameter, atrial dilatation and increased expression of markers of hypertrophy and inflammation. Histologically, no fibrosis was found in the left atrium. But atrial gene expression related to fibrosis was increased. Minor changes related to electrical remodeling were observed. AF inducibility was not different between the groups. Left ventricular end diastolic pressures were increased and correlated with the severity of atrial remodeling but not with AF induction., Conclusion: Permanent ventricular pressure overload by TAC induced atrial remodeling, including hypertrophy, dilatation and inflammation. The extent of atrial remodeling was directly related to LVEDP and not duration of TAC per se.

Aims: Atrial fibrillation (AF) and heart failure often co-exist. It is unknown whether the sequence in which AF and heart failure develop is of significance regarding prognosis. We assessed the prognosis of AF patients hospitalized for heart failure based on the timing of AF and heart failure development., Methods and Results: Consecutive AF patients hospitalized for heart failure were included. Patients who had developed AF before or consecutively with heart failure ('AF first') were compared with patients who had developed heart failure before AF ('heart failure first'). The primary endpoint was a composite of cardiovascular hospitalization or all-cause mortality. The majority of patients hospitalized for AF and heart failure consisted of patients who had developed AF first (137 of 182 patients, 75%, vs. 45 of 182 patients, 25%). The two groups were similar regarding age and gender, but patients with AF first less often had coronary artery disease and had higher ejection fractions than patients with heart failure first (39 ± 14% vs. 32 ± 13%, P = 0.004). During 16 ± 11 months follow-up, the primary composite endpoint occurred less often in patients with AF first than in patients with heart failure first (49.6% vs. 77.7% of patients, P = 0.001). Development of AF first remained beneficial regarding the primary endpoint on multivariable analysis (adjusted hazard ratio 0.50, 95% confidence interval 0.29-0.86, P = 0.01)., Conclusion: The majority of patients hospitalized for AF and heart failure consisted of patients who had developed AF first. Prognosis in these patients was relatively benign as compared with those who had developed heart failure first.

Aims: Outcome of rhythm control in atrial fibrillation (AF) is still poor due to various mechanisms involved in the initiation and perpetuation of AF. Differences in timing of AF recurrence may depend on different types of mechanisms. The aim of this study was to assess the mechanisms involved in early AF recurrence in patients with short-lasting AF., Methods and Results: Patients with short-lasting persistent AF undergoing rhythm control (n= 100) were included. Markers of mechanisms involved in the initiation and perpetuation of AF were assessed, including clinical factors, echocardiographic parameters, and biomarkers. Primary endpoint was early AF recurrence (recurrence <1 month). Secondary endpoint was progression to permanent AF. Median total AF history was short: 4.2 months. Early AF recurrences occurred in 30 patients (30%) after a median of 6 (inter-quartile range 2-14) days. Baseline log(2) interleukin (IL)-6 [adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI) 1.0-1.7, P= 0.02] and present or previous smoking (adjusted HR 3.6, 95% CI 1.2-10.9, P= 0.03) were independently associated with early AF recurrence, suggesting that inflammation played an important role in early recurrences. Atrial fibrillation became permanent in 29 patients (29%). Baseline transforming growth factor-β1, left ventricular ejection fraction, and early AF recurrence were independently associated with progression to permanent AF., Conclusion: In patients with short-lasting AF, early AF recurrence seemed to be associated with inflammation as represented by IL-6. Treatment aimed against inflammation may therefore prevent early AF recurrences, which can improve rhythm control outcome.

Aims: The aim of this study was to investigate the prognostic value of natriuretic peptides and atrial fibrillation (AF) on response to cardiac resynchronization therapy (CRT) and mortality., Methods and Results: This study included 338 consecutive CRT patients. Response to CRT was defined as a reduction in left ventricular end-systolic volume of ≥15% in the absence of death at 6-month follow-up. During follow-up (27 ± 19 months), 139 patients (41%) had AF, being new onset in 40 patients (21%). Forty-two patients (12%) had permanent AF. Response to CRT was observed in 168 of 302 patients (56%): 60 of 123 patients (43%) with AF vs. 108 of 179 patients (60%) without AF (P = 0.047). Low baseline atrial natriuretic peptide (ANP) [odds ratio for log(2) ANP 0.49, 95% confidence interval (CI) 0.35-0.68, P < 0.001] and large left ventricular end-systolic volume (odds ratio for every 50 mL 1.40, 95% CI 1.09-1.79, P = 0.009) were independent predictors of response. Neither the presence of AF nor the increase in AF burden independently predicted response. Ninety patients (27%) died; 50 patients (36%) with AF vs. 40 patients (20%) without AF (log rank P = 0.029). Important predictors of all-cause mortality were new-onset AF (hazard ratio 8.11, 95% CI 3.31-19.85, P < 0.001), permanent AF (hazard ratio 3.19, 95% CI 1.61-6.30, P = 0.001), and baseline N-terminal pro-B-type natriuretic peptide (NT-proBNP) (hazard ratio for log(2) NT-proBNP 0.77, 95% CI 0.66-0.90, P = 0.001)., Conclusion: In patients treated with CRT, lower ANP and larger left ventricular end-systolic volume were independent predictors of response. New-onset AF, permanent AF, and NT-proBNP were independently associated with increased all-cause mortality.

Structural remodelling occurring before, due to the underlying heart disease, and during atrial fibrillation (AF) sets the stage for permanent AF. Current therapy in AF aims to maintain sinus rhythm in symptomatic patients, but outcome is unfortunately poor. Stretch of the atria is a main contributor to atrial remodelling. In this review, we describe different aspects of structural remodelling as seen in animal models and in patients with AF, including atrial enlargement, cellular hypertrophy, dedifferentiation, fibrosis, apoptosis, and loss of contractile elements. In the second part, we describe downstream signals of mechanical stretch and their contribution to AF and structural remodelling. Ultimately, knowledge of mechanisms underlying structural remodelling may help to identify new pharmacological targets for AF prevention.

Background: Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60-70% of patients., Objectives: To study exercise-related factors predicting response to CRT., Methods: We retrospectively examined consecutive patients in whom a CRT device was implanted. All underwent cardiopulmonary exercise testing prior to implantation and after 6 months. The occurrence of chronotropic incompetence and heart rates exceeding the upper rate of the device, thereby compromising biventricular stimulation, was studied. Response was defined as a decrease in LVESV of 10% or more after 6 months., Results: We included 144 patients. After 6 months 86 (60%) patients were responders. Peak VO2 significantly increased in responders. Chronotropic incompetence was more frequently seen in nonresponders (21 [36%] vs 9 [10%], P = 0.03), mostly in patients in SR. At moderate exercise, defined as 25% of the maximal exercise tolerance, that is, comparable to daily life exercise, nonresponders more frequently went above the upper rate of the device (13 [22%] vs 2 [3%], P < 0.0001), most of whom were patients in permanent AF. Multivariate analysis revealed heart rates not exceeding the upper rate of the device during moderate exercise (OR 15.8 [3.3-76.5], P = 0.001) and nonischemic cardiomyopathy (OR 2.4 [1.0-5.7], P = 0.04) as predictive for response., Conclusions: Heart rate exceeding the upper rate during moderate exercise is an independent predictor for nonresponse to CRT in patients with AF, whereas chronotropic incompetence is a predictor for patients in SR.

Aims: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure and sinus rhythm (SR), but its value in atrial fibrillation (AF) remains unclear. Furthermore, response to CRT may be difficult to predict in these patients. The aim of our study was to investigate whether predictors for CRT success differ between patients with AF and SR and to study the influence of present or developing AF on response to CRT., Methods and Results: We examined consecutive patients in whom CRT was implanted disregarding the atrial rhythm. Atrial fibrillation was defined as either current or earlier AF, response to CRT was defined as a decrease in the left ventricular end-systolic volume of > or = 10% after 6 months. Total atrial conduction time (TACT), a measure to predict the risk of developing AF, was determined by echocardiography. We included 114 patients, of whom 56 (49%) were known with AF (23 current AF and 33 earlier AF). The other 58 patients had no history of AF. After 6 months, response in current and earlier AF and that in SR patients was comparable (56, 58 and 55%, respectively). In AF patients, multivariate analysis revealed a shorter TACT at baseline [odds ratio (OR) 16.7 (1.5-185.3), P = 0.02] and an interventricular mechanical delay (IVMD) > 40 ms [OR 10.4 (1.0-110.9), P = 0.05] as predictors for response. Non-responders more frequently suffered from new-onset AF (P = 0.02)., Conclusion: Failure to CRT is associated with new-onset AF. Total atrial activation time may be a parameter to predict response in AF patients.

Background: Atrial fibrillation (AF) is common in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and has a negative impact on outcome. Reliable data on prevalence, incidence, and detection of AF from contemporary, prospective HFmrEF/HFpEF studies are scarce. Methods: This was a prespecified sub-analysis from a prospective, multicenter study. Patients with HFmrEF/HFpEF underwent 12-lead electrocardiography (ECG), 24 h Holter monitoring, and received an implantable loop recorder (ILR) at the study start. During the 2 year follow-up, rhythm monitoring was performed via ILR, yearly ECG, and two yearly 24 h Holter monitors. Results: A total of 113 patients were included (mean age 73 ± 8 years, 75% HFpEF). At baseline, 70 patients (62%) had a diagnosis of AF: 21 paroxysmal, 18 persistent, and 31 permanent AF. At study start, 45 patients were in AF. Of the 43 patients without a history of AF, 19 developed incident AF during a median follow-up of 23 [15–25] months (44%; incidence rate 27.1 (95% confidence interval 16.3–42.4) per 100 person-years). Thus, after the 2-year follow-up, 89 patients (79%) had a diagnosis of AF. In 11/19 incident AF cases (i.e., 58%), AF was solely detected on the ILR. Yearly 12-lead ECG detected six incident AF cases and four of these cases were also detected on two yearly 24 h Holter monitors. Two incident AF cases were detected on an unplanned ECG/Holter. Conclusions: Atrial fibrillation is extremely common in heart failure with HFmrEF/HFpEF and may inform on symptom evaluation and treatment options. AF screening with an ILR had a much higher diagnostic yield than conventional modalities. [ABSTRACT FROM AUTHOR]

Aims: The primary aim of the VIP‐HF study was to examine the incidence of sustained ventricular tachyarrhythmias (VTs) in heart failure (HF) with mid‐range (HFmrEF) or preserved ejection fraction (HFpEF). Secondary aims were to examine the incidence of non‐sustained VTs, bradyarrhythmias, HF hospitalizations and mortality. Methods and results: This was an investigator‐initiated, prospective, multicentre, observational study of patients with HF and left ventricular ejection fraction (LVEF) >40%. Patients underwent extensive phenotyping, after which an implantable loop recorder was implanted. We enrolled 113 of the planned 250 patients [mean age 73 ± 8 years, 51% women, New York Heart Association class II/III 54%/46%, median N‐terminal pro B‐type natriuretic peptide 1367 (710–2452) pg/mL and mean LVEF 54 ± 6%; 75% had LVEF >50%]. Eighteen percent had non‐sustained VTs and 37% had atrial fibrillation on Holter monitoring. During a median follow‐up of 657 (219–748) days, the primary endpoint of sustained VT was observed in one patient. The incidence of the primary endpoint was 0.6 (95% confidence interval 0.2–3.5) per 100 person‐years. The incidence of the secondary endpoint of non‐sustained VT was 11.5 (7.1–18.7) per 100 person‐years. Five patients developed bradyarrhythmias [3.2 (1.4–7.5) per 100 person‐years], three were implanted with a pacemaker. In total, 23 patients (20%) were hospitalized for HF [16.3 (10.9–24.4) per 100 person‐years]. Fourteen patients (12%) died [8.7 (5.2–14.7) per 100 person‐years]; 10 due to cardiovascular causes, and four sudden deaths, one with implantable loop recorder‐confirmed bradyarrhythmias as terminal event, three others undetermined. Conclusion: Despite the lower than expected number of included patients, the incidence of sustained VTs in HFmrEF/HFpEF was low. Clinically relevant bradyarrhythmias were more often observed than expected. [ABSTRACT FROM AUTHOR]

Aims: Atrial fibrillation (AF) often starts as a paroxysmal self-terminating arrhythmia. Limited information is available on AF patterns and episode duration of paroxysmal AF. In paroxysmal AF patients, we longitudinally studied the temporal AF patterns, the association with clinical characteristics, and prevalence of AF progression.Methods and Results: In this interim analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) registry, 202 patients with paroxysmal AF were followed with continuous rhythm monitoring (implantable loop recorder or pacemaker) for 6 months. Mean age was 64 ± 9 years, 42% were women. Atrial fibrillation history was 2.1 (0.5-4.4) years, CHA2DS2-VASc 1.9 ± 1.3, 101 (50%) had hypertension, 69 (34%) heart failure. One-third had no AF during follow-up. Patients with long episodes (>12 hours) were often men with more comorbidities (heart failure, coronary artery disease, higher left ventricular mass). Patients with higher AF burden (>2.5%) were older with more comorbidities (worse renal function, higher calcium score, thicker intima media thickness). In 179 (89%) patients, 1-year rhythm follow-up was available. On a quarterly basis, average daily AF burden increased from 3.2% to 3.8%, 5.2%, and 6.1%. Compared to the first 6 months, 111 (62%) patients remained stable during the second 6 months, 39 (22%) showed progression to longer AF episodes, 8 (3%) developed persistent AF, and 29 (16%) patients showed AF regression.Conclusions: In paroxysmal AF, temporal patterns differ suggesting that paroxysmal AF is not one entity. Atrial fibrillation burden is low and determined by number of comorbidities. Atrial fibrillation progression occurred in a substantial number.Trial Registration Number: Clinicaltrials.gov identifier NCT02726698. [ABSTRACT FROM AUTHOR]

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are very common conditions, particularly in the elderly. However, the mechanisms underlying the two disorders, including their intricate interaction have not been fully resolved. Here, our aim is to review the evidence on the role of the two types of senile amyloidosis in this connection. Two types of senile amyloidosis can be identified: wild-type transthyretin (TTR)-derived amyloidosis (ATTRwt) and isolated atrial amyloidosis (IAA). ATTRwt is an underlying condition that is being increasingly recognized in patients with HFpEF and often accompanied by AF. IAA is an established cause of AF, adding to the mechanism problem. New diagnostic and therapeutic possibilities have emerged that may facilitate clinical management of (senile) amyloidosis, which in turn may have implications for the management of HFpEF and AF. View large Download slide View large Download slide [ABSTRACT FROM AUTHOR]

Heart failure has become the cardiovascular epidemic of the century. The European Journal of Heart Failure is dedicated to the advancement of knowledge in the field of heart failure management. In 2012 and 2013, several pioneering scientific discoveries and paradigm-shifting clinical trials have been published. In the current paper, we will discuss the most significant novel insights into the pathophysiology, diagnosis, and treatment of heart failure that were published during this period. All relevant research areas are discussed, including pathophysiology, co-morbidities, arrhythmias, biomarkers, clinical trials, and device therapy, including left ventricular assist devices. [ABSTRACT FROM AUTHOR]

Atrial fibrillation ( AF) often occurs in the presence of an underlying disease. These underlying diseases cause atrial remodelling, which make the atria more susceptible to AF. Stretch is an important mediator in the remodelling process. The aim of this study was to develop an atrial cell culture model mimicking remodelling due to atrial pressure overload. Neonatal rat atrial cardiomyocytes ( NRAM) were cultured and subjected to cyclical stretch on elastic membranes. Stretching with 1 Hz and 15% elongation for 30 min. resulted in increased expression of immediate early genes and phosphorylation of Erk and p38. A 24-hr stretch period resulted in hypertrophy-related changes including increased cell diameter, reinduction of the foetal gene program and cell death. No evidence of apoptosis was observed. Expression of atrial natriuretic peptide, brain natriuretic peptide and growth differentiation factor-15 was increased, and calcineurin signalling was activated. Expression of several potassium channels was decreased, suggesting electrical remodelling. Atrial stretch-induced change in skeletal α-actin expression was inhibited by pravastatin, but not by eplerenone or losartan. Stretch of NRAM results in elevation of stress markers, changes related to hypertrophy and dedifferentiation, electrical remodelling and cell death. This model can contribute to investigating the mechanisms involved in the remodelling process caused by stretch and to the testing of pharmaceutical agents. [ABSTRACT FROM AUTHOR]

Aims: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure and sinus rhythm (SR), but its value in atrial fibrillation (AF) remains unclear. Furthermore, response to CRT may be difficult to predict in these patients. The aim of our study was to investigate whether predictors for CRT success differ between patients with AF and SR and to study the influence of present or developing AF on response to CRT. [ABSTRACT FROM PUBLISHER]