Evaluating subclinical left ventricular and left atrial dysfunction in idiopathic atrial fibrillation: A speckle-tracking based strain-analysis.

OBJECTIVE: A subset of patients with atrial fibrillation (AF) presents without established AF risk factors and normal left ventricular (LV) systolic function, called idiopathic AF (IAF). Traditionally, echocardiography derived LV dimensions and ejection fraction (EF) are used to exclude LV dysfunction in IAF, but their sensitivity is limited. Our objective is to evaluate the presence of subtle alterations in LV function despite normal LVEF in patients with IAF compared to healthy controls, using speckle-tracking echocardiography (STE) based global longitudinal strain (GLS). METHODS: Standard transthoracic echocardiography was performed in 80 patients with IAF and 129 healthy controls. Patients with overt cardiac disease as well as known established AF risk factors were excluded. STE analysis was performed to assess GLS of the LV, and left atrial strain (LAS). RESULTS: LVEF was normal and comparable between patients with IAF and healthy controls (63 ± 4% for both groups; p = 0.801). Mean GLS was within normal limits for both groups but statistically significantly more negative in patients with IAF (-20.6 ± 2.5% vs. -19.7 ± 2.5%; p = 0.016), however not when indexed for ventricular cycle length (p = 0.784). No differences in LA volume or non-indexed LAS were seen in patients with IAF compared to healthy controls. CONCLUSIONS: In this selected group of IAF patients, STE did not detect any overt LV or LA dysfunction compared to healthy controls. Thus, IAF occurred in these patients not only in the absence of established AF risk factors but also without evidence of ventricular or atrial dysfunction.

360° Virtual reality to improve patient education and reduce anxiety towards atrial fibrillation ablation.

AIMS: Evaluation of (i) the effects of a virtual reality (VR) preprocedural patient education video on information provision, procedure-related knowledge, satisfaction, and the level of worries in patients planned for atrial fibrillation (AF) ablation and (ii) the feasibility of a disposable cardboard VR viewer for home use in this setting. METHODS AND RESULTS: In this prospective observational cohort study, patients were alternatively assigned in a 1:1 ratio to the control or VR group. Controls received standard preprocedural information. VR group received standard information and a VR video (via in-hospital VR headset and disposable cardboard). The Amsterdam Preoperative Anxiety and Information Scale (APAIS) together with additional questions concerning procedural experience and satisfaction was completed pre- and post-ablation. Of 134 patients [38.1% female, aged 66 (58-72) years] included, 49.2% were assigned to the control and 50.7% to the VR group. The number of patients that worried about the ablation procedure was lower in VR than in control patients (19.1% vs. 40.9%, P = 0.006). More VR females than males had worries about the procedure (34.8% vs. 11.1%, P = 0.026). The number of VR patients that were satisfied with the preprocedural information provision was higher post-ablation than pre-ablation (83.3% vs. 60.4%, P = 0.007). In total, 59.4% reported that the disposable cardboard was easy to use and led to a discussion with relatives in 68.8%. CONCLUSION: In patients scheduled for AF ablation, a VR preprocedural educational video led to better information provision and procedure-related knowledge, higher satisfaction, and less worries regarding the procedure. The disposable cardboard was feasible for home use.

A new efficient and integrated pathway for patient evaluation prior to atrial fibrillation ablation.

AIMS: In this quality improvement project, a care pathway for patients considered for atrial fibrillation (AF) ablation was optimized with the goals to improve the patient journey and simultaneously integrate prospective data collection into the clinical process. METHODS AND RESULTS: The Lean Six Sigma approach was used to map the pre-existing process, identify constraints, and formulate countermeasures. The percentage of patients going through the full pre-ablation preparation that eventually underwent AF ablation, number of hospital visits and consultations, pathway compliance, and completeness of scientific data were measured before and after pathway optimization. Constraints in the process were (i) lack of standardized processes, (ii) inefficient use of resources, (iii) lack of multidisciplinary integration, (iv) lack of research integration, and (v) suboptimal communication. The impact of the corresponding countermeasures (defining a uniform process, incorporating 'go/no-go' moment, introducing a 'one-stop-shop', integrating prospective data collection, and improving communication) was studied for 33 patients before and 26 patients after pathway optimization. After optimization, the percentage of patients receiving a full pre-ablation preparation that eventually underwent AF ablation increased from 59% to 94% (P < 0.01). Fewer hospital visits (3.2 ± 1.2 vs. 2.3 ± 0.8, P = 0.01) and electrophysiologist consultations (1.8 ± 0.7 vs. 1.0 ± 0.3, P < 0.01) were required after pathway optimization. Pathway compliance and complete collection of scientific data increased significantly (3% vs. 73%, P < 0.01 and 15% vs. 73%, P < 0.01, respectively). CONCLUSION: The optimization project resulted in a more efficient evaluation of patients considered for AF ablation. The new more efficient process includes prospective data collection and facilitates easy conduct of research studies focused on improvements of patient outcomes.

Long-term outcome of targeted therapy of underlying conditions in patients with early persistent atrial fibrillation and heart failure: data of the RACE 3 trial.

AIMS: The Routine vs. Aggressive risk factor driven upstream rhythm Control for prevention of Early persistent atrial fibrillation (AF) in heart failure (HF) (RACE 3) trial demonstrated that targeted therapy of underlying conditions improved sinus rhythm maintenance at 1 year. We now explored the effects of targeted therapy on the additional co-primary endpoints; sinus rhythm maintenance and cardiovascular outcome at 5 years. METHODS AND RESULTS: Patients with early persistent AF and mild-to-moderate stable HF were randomized to targeted or conventional therapy. Both groups received rhythm control therapy according to guidelines. The targeted group additionally received four therapies: angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers (ARBs), statins, mineralocorticoid receptor antagonists (MRAs), and cardiac rehabilitation. The presence of sinus rhythm and cardiovascular morbidity and mortality at 5-year follow-up were assessed. Two hundred and sixteen patients consented for long-term follow-up, 107 were randomized to targeted and 109 to conventional therapy. At 5 years, MRAs [76 (74%) vs. 10 (9%) patients, P < 0.001] and statins [81 (79%) vs. 59 (55%), P < 0.001] were used more in the targeted than conventional group. Angiotensin-converting enzyme inhibitors/ARBs and physical activity were not different between groups. Sinus rhythm was present in 49 (46%) targeted vs. 43 (39%) conventional group patients at 5 years (odds ratio 1.297, lower limit of 95% confidence interval 0.756, P = 0.346). Cardiovascular mortality and morbidity occurred in 20 (19%) in the targeted and 15 (14%) conventional group patients, P = 0.353. CONCLUSION: In patients with early persistent AF and HF superiority of targeted therapy in sinus rhythm maintenance could not be preserved at 5-year follow-up. Cardiovascular outcome was not different between groups. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00877643.

Echocardiography-derived total atrial conduction time (PA-TDI duration): risk stratification and guidance in atrial fibrillation management.

Atrial fibrillation (AF) is a major cause of cardiovascular morbidity and mortality. To early detect and to avoid AF-related complications, several cardiac imaging modalities and approaches aim to quantify the severity of the underlying atrial cardiomyopathy (i.e., the extent of atrial remodeling). However, most established cardiac imaging modalities just incorporate single components of atrial remodeling and do not reflect the complete multifactorial process, which may contribute to their limited predictive value. Echocardiography-derived PA-TDI duration is a sophisticated echocardiographic parameter to assess total atrial conduction time and directly reflects both electrical and structural changes to the atria. Therefore, PA-TDI duration provides a more comprehensive quantification of the extent of atrial remodeling than other imaging modalities. In this article we review the role of PA-TDI duration as a marker of atrial remodeling and summarize the available data on PA-TDI duration to identify patients at risk for AF, as well as to guide AF management. Moreover, we discuss how to assess PA-TDI duration and provide recommendations on the implementation of PA-TDI duration into routine clinical care.

The relation between the atrial blood supply and the complexity of acute atrial fibrillation.

BACKGROUND: Patients with a history of myocardial infarction and coronary artery disease (CAD) have a higher risk of developing AF. Conversely, patients with atrial fibrillation (AF) have a higher risk of developing myocardial infarction, suggesting a link in underlying pathophysiology. The aim of this study was to assess whether coronary angiographic parameters are associated with a substrate for AF in patients without a history of AF. METHODS: During cardiac surgery in 62 patients (coronary artery bypass grafting (CABG;n = 47), aortic valve replacement (AVR;n = 9) or CABG + AVR (n = 6)) without a history of clinical AF (age 65.4 ± 8.5 years, 26.2% female), AF was induced by burst pacing. The preoperative coronary angiogram (CAG) was assessed for the severity of CAD, and the adequacy of atrial coronary blood supply as quantified by a novel scoring system including the location and severity of right coronary artery disease in relation to the right atrial branches. Epicardial mapping of the right atrium (256 unipolar electrodes) was used to assess the complexity of induced AF. RESULTS: There was no association between the adequacy of right atrial coronary blood supply on preoperative CAG and AF complexity parameters. Multivariable analysis revealed that only increasing age (B0.232 (0.030;0.433),p = 0.03) and the presence of 3VD (B3.602 (0.187;7.018),p = 0.04) were independently associated with an increased maximal activation time difference. CONCLUSIONS: The adequacy of epicardial right atrial blood supply is not associated with increased complexity of induced atrial fibrillation in patients without a history of clinical AF, while age and the extent of ventricular coronary artery disease are.

Antiarrhythmic drugs in patients with early persistent atrial fibrillation and heart failure: results of the RACE 3 study.

AIMS: Maintaining sinus rhythm in patients with persistent atrial fibrillation (AF) is challenging. We explored the efficacy of class I and III antiarrhythmic drugs (AADs) in patients with persistent AF and mild to moderate heart failure (HF). METHODS AND RESULTS: In the RACE 3 trial, patients with early persistent symptomatic AF and short history of mild to moderate HF with preserved or reduced left ventricular ejection fraction (LVEF) were randomized to targeted or conventional therapy. Both groups received AF and HF guideline-driven treatment. Additionally, the targeted-group received mineralocorticoid receptor antagonists, statins, angiotensin-converting enzyme inhibitors and/or receptor blockers, and cardiac rehabilitation. Class I and III AADs could be instituted in case of symptomatic recurrent AF. Eventually, pulmonary vein isolation could be performed. Primary endpoint was sinus rhythm on 7-day Holter after 1-year. Included were 245 patients, age 65 ± 9 years, 193 (79%) men, AF history was 3 (2-6) months, HF history 2 (1-4) months, 72 (29.4%) had HF with reduced LVEF. After baseline electrical cardioversion (ECV), 190 (77.6%) had AF recurrences; 108 (56.8%) received class I/III AADs; 19 (17.6%) flecainide, 36 (33.3%) sotalol, 3 (2.8%) dronedarone, 50 (46.3%) amiodarone. At 1-year 73 of 108 (68.0%) patients were in sinus rhythm, 44 (40.7%) without new AF recurrences. Maintenance of sinus rhythm was significantly better with amiodarone [n = 29/50 (58%)] compared with flecainide [n = 6/19 (32%)] and sotalol/dronedarone [n = 9/39 (23%)], P = 0.0064. Adverse events occurred in 27 (25.0%) patients, were all minor and reversible. CONCLUSION: In stable HF patients with early persistent AF, AAD treatment was effective in nearly half of patients, with no serious adverse effects reported.

Long-term intermittent versus short continuous heart rhythm monitoring for the detection of atrial fibrillation recurrences after catheter ablation.

BACKGROUND: The utility of long-term intermittent heart rhythm monitoring after atrial fibrillation (AF) ablation remains unclear. Therefore, we compared the efficacy and usability of long-term intermittent (AliveCor Kardia® (ACK)) versus short continuous (Holter) heart rhythm monitoring for the detection of AF recurrences after AF ablation and evaluated ACK accuracy to detect AF. METHODS: Patients were provided with Holter (for ≥24 h) simultaneously with an ACK (4 weeks) used three times a day and in case of symptoms. The primary endpoint was the difference in proportion of patients diagnosed with recurrent AF by ACK as compared to Holter monitoring. Secondary endpoints were the usability (System Usability Scale and a four-item questionnaire) of ACK and Holter monitoring; and the accuracy of the ACK algorithm for AF detection. RESULTS: Out of 126 post-ablation patients, 115 (91.3%; 35 females, median age 64.0 [58.0-68.0] years) transmitted overall 7838 ACK ECG recordings. ACK and Holter monitoring detected 29 (25.2%) and 17 (14.8%) patients with AF recurrences, respectively (p < 0.001). More than 2 weeks of ACK monitoring did not have additional diagnostic yield for detection of AF recurrences. Patients graded ACK higher than Holter monitoring and found ACK more convenient in daily usage than Holter (p < 0.001). Sensitivity and specificity of ACK for AF detection were 95.3% and 97.5%, respectively. CONCLUSIONS: Long-term intermittent monitoring by ACK more effectively detects AF recurrences after AF ablation and has a higher patients' usability than short continuous Holter monitoring. ACK showed a high accuracy to detect AF.

Biomarkers Associated With Aortic Valve Calcification: Should We Focus on Sex Specific Processes?

OBJECTIVE: Circulating biomarkers are useful in detection and monitoring of cardiovascular diseases. However, their role in aortic valve disease is unclear. Mechanisms are rapidly elucidated and sex differences are suggested to be involved. Therefore, we sought to identify biomarkers involved in aortic valve calcification (AVC) stratified by sex. METHODS: Blood samples of 34 patients with AVC (without further overt cardiovascular disease, including absence of hemodynamic consequences of valvular calcification) were compared with 136 patients without AVC. AVC was determined using computed tomography calcium scoring. Circulating biomarkers were quantified using a novel antibody-based method (Olink Proseek Multiplex Cardiovascular Panel I) and 92 biomarkers were compared between patients with and without AVC. RESULTS: In the overall population, Interleukin-1 Receptor Antagonist and pappalysin-1 were associated with increased and decreased odds of having AVC. These differences were driven by the male population [IL1RA: OR 2.79 (1.16-6.70), p = 0.022; PAPPA: OR 0.30 (0.11-0.84), p = 0.021]. Furthermore, TNF-related activation-induced cytokine (TRANCE) and fibroblast growth factor-23 were associated decreased odds of having AVC, and monocyte chemotactic protein-1 was associated with increased odds of having AVC [TRANCE: OR 0.32 (0.12-0.80), p = 0.015; FGF23: OR 0.41 (0.170-0.991), p = 0.048; MCP1: OR 2.64 (1.02-6.81), p = 0.045]. In contrast, galanin peptides and ST2 were associated with increased odds of having AVC in females [GAL: OR 12.38 (1.31-116.7), p = 0.028; ST2: OR13.64 (1.21-153.33), p = 0.034]. CONCLUSION: In this exploratory study, we identified biomarkers involved in inflammation, fibrosis and calcification which may be associated with having AVC. Biomarkers involved in fibrosis may show higher expression in females, whilst biomarkers involved in inflammation and calcification could associate with AVC in males.

Variation in the Association between Antineoplastic Therapies and Venous Thromboembolism in Patients with Active Cancer.

BACKGROUND: Venous thromboembolism (VTE) is a major cause of death in cancer patients. Although patients with cancer have numerous risk factors for VTE, the relative contribution of cancer treatments is unclear. OBJECTIVE: The objective of this study is to evaluate the association between cancer therapies and the risk of VTE. METHODS: From UK Clinical Practice Research Datalink, data on patients with first cancer diagnosis between 2008 and 2016 were extracted along with information on hospitalization, treatments, and cause of death. Primary outcome was active cancer-associated VTE. To establish the independent effects of risk factors, adjusted subhazard ratios (adj-SHR) were calculated using Fine and Gray regression analysis accounting for death as competing risk. RESULTS: Among 67,801 patients with a first cancer diagnosis, active cancer-associated VTE occurred in 1,473 (2.2%). During a median observation time of 1.2 years, chemotherapy, surgery, hormonal therapy, radiation therapy, and immunotherapy were given to 71.1, 37.2, 17.2, 17.5, and 1.4% of patients with VTE, respectively. The active cancers associated with the highest risk of VTE-as assessed by incidence rates-included pancreatic cancer, brain cancer, and metastatic cancer. Chemotherapy was associated with an increased risk of VTE (adj-SHR: 3.17, 95% confidence interval [CI]: 2.76-3.65) while immunotherapy with a not significant reduced risk (adj-SHR: 0.67, 95% CI: 0.30-1.52). There was no association between VTE and radiation therapy (adj-SHR: 0.91, 95% CI: 0.65-1.27) and hormonal therapies. CONCLUSION: VTE risk varies with cancer type. Chemotherapy was associated with an increased VTE risk, whereas with radiation and immunotherapy therapy, an association was not confirmed.

Short-Term Hemodynamic and Electrophysiological Effects of Cardiac Resynchronization by Left Ventricular Septal Pacing.

BACKGROUND: Cardiac resynchronization therapy (CRT) is usually performed by biventricular (BiV) pacing. Previously, feasibility of transvenous implantation of a lead at the left ventricular (LV) endocardial side of the interventricular septum, referred to as LV septal (LVs) pacing, was demonstrated. OBJECTIVES: The authors sought to compare the acute electrophysiological and hemodynamic effects of LVs with BiV and His bundle (HB) pacing in CRT patients. METHODS: Temporary LVs pacing (transaortic approach) alone or in combination with right ventricular (RV) (LVs+RV), BiV, and HB pacing was performed in 27 patients undergoing CRT implantation. Electrophysiological changes were assessed using electrocardiography (QRS duration), vectorcardiography (QRS area), and multielectrode body surface mapping (standard deviation of activation times [SDAT]). Hemodynamic changes were assessed as the first derivative of LV pressure (LVdP/dtmax). RESULTS: As compared with baseline, LVs pacing resulted in a larger reduction in QRS area (to 73 ± 22 µVs) and SDAT (to 26 ± 7 ms) than BiV (to 93 ± 26 µVs and 31 ± 7 ms; both p < 0.05) and LVs+RV pacing (to 108 ± 37 µVs; p < 0.05; and 29 ± 8 ms; p = 0.05). The increase in LVdP/dtmax was similar during LVs and BiV pacing (17 ± 10% vs. 17 ± 9%, respectively) and larger than during LVs+RV pacing (11 ± 9%; p < 0.05). There were no significant differences between basal, mid-, or apical LVs levels in LVdP/dtmax and SDAT. In a subgroup of 16 patients, changes in QRS area, SDAT, and LVdP/dtmax were comparable between LVs and HB pacing. CONCLUSIONS: LVs pacing provides short-term hemodynamic improvement and electrical resynchronization that is at least as good as during BiV and possibly HB pacing. These results indicate that LVs pacing may serve as a valuable alternative for CRT.

Frequency and Determinants of Spontaneous Conversion to Sinus Rhythm in Patients Presenting to the Emergency Department with Recent-onset Atrial Fibrillation: A Systematic Review.

The exact frequency and clinical determinants of spontaneous conversion (SCV) in patients with symptomatic recent-onset AF are unclear. The aim of this systematic review is to provide an overview of the frequency and determinants of SCV of AF in patients presenting at the emergency department. A comprehensive literature search for studies about SCV in patients presenting to the emergency department with AF resulted in 25 articles - 12 randomised controlled trials and 13 observational studies. SCV rates range between 9-83% and determinants of SCV also varied between studies. The most important determinants of SCV included short duration of AF (<24 or <48 hours), low number of episodes, normal atrial dimensions and absence of previous heart disease. The large variation in SCV rate and determinants of SCV was related to differences in duration of the observation period, inclusion and exclusion criteria and in variables used in the prediction models.

Incident Atrial Fibrillation, Dementia and the Role of Anticoagulation: A Population-Based Cohort Study.

INTRODUCTION: Atrial fibrillation (AF) is associated with dementia. Anticoagulation may modify this relationship, but it is unclear if this is due to stroke reduction alone. METHODS: Age- and sex-matched individuals from the U.K. Clinical Practice Research Datalink (2008-2016) with and without an incident diagnosis of AF were followed for a new dementia diagnosis. We estimated adjusted hazard ratios (aHRs) for incident dementia diagnosis in the AF cohort, overall and stratified by anticoagulation status, using the matched non-AF cohorts as reference. We performed a sensitivity analysis excluding individuals with stroke/transient ischaemic attack (TIA) before the observation period. RESULTS: Over 193,082 person-years (mean follow-up 25.7 ± 0.1 months), 347/15,276 AF (2.3%) and 1,085/76,096 non-AF (1.4%) were newly diagnosed with dementia (aHR, 1.31, 95% confidence interval, 1.15-1.49). The AF group had more co-morbidity and higher rates of dementia, both with and without anticoagulation, than non-AF. When those with history of stroke/ TIA before the observation period were excluded and those with incident stroke/TIA during the observation period were censored, AF individuals not on anticoagulation had significantly higher rates of dementia compared with non-AF, aHR 1.30 (1.06-1.58). CONCLUSION: Our findings support the hypothesis that AF is a distinct risk factor for dementia, independent of stroke/TIA and other vascular risk factors. In those without stroke/TIA, risk of dementia is increased only in those who are not on anticoagulation, suggesting anticoagulation is protective presumably through reduction of sub-clinical embolic events. Further prospective research is needed to better ascertain the role of anticoagulation amongst targeted therapeutic strategies to reduce cognitive decline in AF.

Targeted therapy of underlying conditions improves quality of life in patients with persistent atrial fibrillation: results of the RACE 3 study.

AIMS: Atrial fibrillation (AF) reduces quality of life (QoL). We aim to evaluate effects of targeted therapy of underlying conditions on QoL in patients with AF and heart failure (HF). METHODS AND RESULTS: The Routine versus Aggressive risk factor driven upstream rhythm Control for prevention of Early atrial fibrillation in heart failure (RACE 3) study randomized patients with early persistent AF and HF to targeted or conventional therapy. Both groups received guideline-driven treatment. The targeted group received four additional therapies: mineralocorticoid receptor antagonists; statins; angiotensin converting enzyme inhibitors and/or receptor blockers; and cardiac rehabilitation including physical activity, dietary restrictions, and counselling. Quality of life was analysed in 230 patients at baseline and 1 year with available Medical Outcomes Study Short-Form Health Survey (SF-36), University of Toronto AF Severity Scale (AFSS) questionnaires, and European Heart Rhythm Association (EHRA) class. Improvements in SF-36 subscales were larger in the targeted group for physical functioning (Δ12 ± 19 vs. Δ6 ± 22, P = 0.007), physical role limitations (Δ32 ± 41 vs. Δ17 ± 45, P = 0.018), and general health (Δ8 ± 16 vs. Δ0 ± 17, P < 0.001). Dyspnoea at rest improved more (Δ-0.8 ± 1.3 vs. Δ-0.4 ± 1.2, P = 0.018) and EHRA class was lower at 1-year follow-up in the targeted group. Patients with AF at 1 year, improvement in physical functioning (Δ9 ± 9 vs. Δ-3 ± 16, P = 0.001), general health (Δ7 ± 16 vs. Δ-7 ± 19, P = 0.004), and social functioning (Δ6 ± 23 vs. Δ-4 ± 16, P = 0.041) were larger in the targeted group. CONCLUSION: A strategy aiming to treat underlying conditions improved QoL more compared with conventional therapy in patients with early persistent AF and HF. Its benefit was even observed in patients in AF at 1 year. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT00877643.

Vascular Calcification and not Arrhythmia in Idiopathic Atrial Fibrillation Associates with Sex Differences in Diabetic Microvascular Injury miRNA Profiles.

BACKGROUND: Atrial Fibrillation (AF) in patients without concomitant cardiovascular pathophysiological disease, is called idiopathic Atrial Fibrillation (iAF). Nonetheless, iAF patients have often times subclinical coronary (micro) vascular dysfunction and, particularly in women, a higher prevalence of subsequent cardiovascular comorbidities. Previously, we identified a plasma miRNA association with diabetes and microvascular injury in Diabetic Nephropathy (DN) patients. Therefore, in this study we assessed whether plasma levels of these diabetic, microvascular injury associated miRNAs reflect microvascular integrity in iAF patients, associated with the presence of paroxysmal arrhythmia or instead are determined by concealed coronary artery disease. METHODS: Circulating levels of a pre-selected set of diabetic, (micro) vascular injury associated miRNAs, were measured in 59 iAF patients compared to 176 Sinus Rhythm (SR) controls. Furthermore, the presence of coronary artery and aortic calcification in each patient was assessed using Cardiac Computed Tomography Angiography (CCTA). RESULTS: Paroxysmal arrhythmia in iAF patients did not result in significant miRNA expression profile differences in iAF patients compared to SR controls. Nonetheless, coronary artery calcification (CAC) was associated with higher levels of miRNAs-103, -125a-5p, -221 and -223 in men. In women, CAC was associated with higher plasma levels of miRNA-27a and miRNA-126 and correlated with Agatston scores. Within the total population, ascending Aortic Calcification (AsAC) patients displayed increased plasma levels of miRNA-221, while women, in particular, demonstrated a Descending Aorta Calcification (DAC) associated increase in miRNA-212 levels. CONCLUSIONS: Diabetic microvascular injury associated miRNAs in iAF are associated with subclinical coronary artery disease in a sex-specific way and confirm the notion that biological sex identifies iAF subgroups that may require dedicated clinical care.

Agatston score of the descending aorta is independently associated with coronary events in a low-risk population.

Objectives: A standard coronary artery calcium scan includes part of the aorta. This additional information is often not included in routine analyses. We aimed to determine the feasibility of assessing the Agatston score of the descending aorta calcification (DAC) on standard coronary calcium scans and the association of this score with coronary events in a low-risk study population. Methods: Between January 2008 and March 2011, 390 consecutive patients who were referred for cardiac CT as part of work-up for pulmonary vein isolation (n=115) or assessment of presence of coronary artery disease (n=275) were included. At baseline, all patients were free of a history of cardiovascular disease. Two independent observers determined the Agatston score of the ascending aorta and descending aorta. Results: A total of 16 patients (4.1%) developed coronary events (acute coronary syndrome (n=6) and symptomatic significant coronary artery disease requiring treatment (n=10)) during a follow-up of 67±12 months, with more events in patients with calcifications in the descending aorta than in those without (8.4% vs 3.7 %; p=0.08). Multivariable Cox regression, corrected for Framingham Risk Score (FRS) and coronary Agatston score (CAC), revealed that DAC was independently associated with coronary events (per 100 units; HR: 1.06, 95% CI 1.02 to 1.09; p=0.001). DAC furthermore increased the identification of patients that will experience a coronary event (area under the curve: 0.68 for FRS only, 0.75 for FRS+CAC and 0.78 for FRS+CAC+DAC). Conclusions: The Agatston score of the descending aorta could be included in the standard analysis of cardiac CT scans of low-risk patients since it holds valuable information for the prediction of coronary events.

Late complications of an atrial septal occluder provoked by anticoagulant therapy.

Late complications of an atrial septal occluder device (ASO) are rare but may be serious. We report a case with extensive hemopericardium five years after ASO implantation most likely triggered by anticoagulant therapy. Although not surgically confirmed, indirect clues for erosion of the atrial wall by the device were the exclusion of other etiologies, lack of recurrence after pericardial drainage and withdrawal of anticoagulants. In addition, multimodality imaging using echocardiography, computed tomography, and cardiac magnetic resonance imaging were helpful to elucidate this unusual cause. Initiation of anticoagulant treatment in patients with an ASO should be carefully balanced and may warrant more frequent echocardiographic follow-up. .

Cardioversion of persistent atrial fibrillation is associated with a 24-hour relapse gap: Observations from prolonged postcardioversion rhythm monitoring.

BACKGROUND: Many recurrences occur after electrical cardioversion (ECV) of atrial fibrillation (AF). Assessment of extent of remodeling and continuous prolonged rhythm monitoring might reveal actionable recurrence mechanisms. HYPOTHESIS: After ECV of AF specific patterns of arrhythmia recurrence can be distinguished. METHODS: All patients who underwent successful ECV due to persistent AF were included. Tissue velocity echocardiography during AF was performed before ECV to study atrial fibrillatory cycle length and fibrillatory velocity. After ECV, the heart rhythm of all patients was monitored 3 times daily during 4 weeks, and timing of recurrence was noted. RESULTS: In total, 50 patients (68% male) were included; mean age was 68 ± 9 years. Median duration of the current AF episode was 102 (range, 74-152) days. Twenty-one (42%) patients showed recurrence of persistent AF. No recurrences occurred during the first 24 hours. There were no differences in clinical characteristics between patients with or without recurrence of AF. However, patients with early recurrence of AF had significantly higher precardioversion wall-motion velocity compared with patients who remained in sinus rhythm (2.8 [1.6-3.6] vs 1.4 [0.9-3.3] cm/s; P = 0.017), whereas atrial fibrillatory cycle length did not differ. CONCLUSIONS: In this study on 50 patients successfully cardioverted for persistent AF, there was a relapse gap of ≥24 hours. This phenomenon has not been well appreciated before and offers an AF-free window of opportunity for electrocardiographically triggered cardiac imaging or complex electrophysiological procedures. Echocardiographic tissue velocity imaging may visualize atrial remodeling relevant to AF recurrence.

The influence of progression of atrial fibrillation on quality of life: a report from the Euro Heart Survey.

Aims: Progression of atrial fibrillation (AF) from paroxysmal to persistent forms is an active field of research. The influence of AF progression on health related quality of life (HRQoL) is currently unknown. We aimed to assess the influence of AF progression on HRQoL, and whether this association is mediated through symptoms, treatment, and major adverse events. Methods and results: In the Euro Heart Survey, 967 patients were included with paroxysmal AF who filled out EuroQoL-5D at baseline and at 1 year follow-up. Those who progressed (n = 132, 13.6%) developed more problems during follow-up than those who did not, on all EuroQoL-5D domains (increase in problems on mobility 20.5% vs. 11.4%; self-care 12.9% vs. 6.2%; usual activities 23.5% vs. 14.0%; pain/discomfort 20.5% vs. 13.7%; and anxiety/depression 22.7% vs. 15.7%; all P < 0.05), leading to a decrease in utility [baseline 0.744 ± 0.26, follow-up 0.674 ± 0.36; difference -0.07 (95% CI [-0.126,-0.013], P = 0.02)]. Multivariate analysis showed that the effect of progression on utility is mediated by a large effect of adverse events [stroke (-0.27 (95% CI [-0.43,-0.11]); P = 0.001], heart failure [-0.12 (95% CI [-0.20,-0.05]); P = 0.001], malignancy (-0.31 (95% CI [-0.56,-0.05]); P = 0.02] or implantation of an implantable cardiac defibrillator [-0.12 (95% CI [-0.23,-0.02]); P = 0.03)], as well as symptomatic AF [-0.04 (95% CI [-0.08,-0.01]); P = 0.008]. Conclusion: AF progression is associated with a decrease in HRQoL. However, multivariate analysis revealed that AF progression itself does not have a negative effect on HRQoL, but that this effect can be attributed to a minor effect of the associated symptoms and a major effect of associated adverse events.

The Biomarkers NT-proBNP and CA-125 are Elevated in Patients with Idiopathic Atrial Fibrillation.

BACKGROUND: Blood biomarkers related to AF could be useful to detect silent AF and to develop stratified strategies for AF prevention. Previous studies identified markers that predict incident AF. However, it is difficult to differentiate whether biomarkers relate to underlying cardiovascular diseases, are generated by the atria in response to an AF episode, or both. We therefore measured a panel of blood biomarkers in patients without overt CVD with and without AF to investigate the association between biomarkers and atrial fibrillation (AF) in patients without overt cardiovascular disease (CVD). METHODS: Blood samples - drawn remote from an AF episode - of 60 patients with AF but without overt forms of CVD (idiopathic AF; iAF) were compared to 120 matched patients with sinus rhythm only. A novel antibody-based method for quantification of blood biomarkers (OlinkProseek Multiplex Cardiovascular) was used to compare 92 biomarkers between the two groups. RESULTS: N-terminal pro-B-type natriuretic peptide (NT-proBNP), Cathepsin L1, Endothelial cell-specific molecule 1, Cancer Antigen-125 (CA-125), Heat shock 27kDa protein, Galanin peptides, Proteinase-activated receptor 1, Stem cell factor, and CD40-ligand were all higher in iAF patients than in SR controls. Both NT-proBNP (OR1.55(1.07-2.25);p=0.022) and CA-125 (OR1.68(1.07-2.64);p=0.026) were independently associated with iAF. CONCLUSIONS: This exploratory study, investigating over 90 cardiovascular blood biomarkers in patients without known CVD, identified one established biomarker for paroxysmal AF, NT-proBNP, and a novel marker, CA-125. CA-125 - previously unrelated to paroxysmal AF in an otherwise healthy population - may thus be a potential indicator of remote paroxysms of AF.