Increased plasma levels of NT-proBNP, Troponin T and GDF-15 are driven by persistent AF and associated comorbidities: Data from the AF-RISK study.

Atrial fibrillation (AF) is a progressive disease, and early recognition and management may reflect an important strategy to reduce its disease burden. In this study, we evaluated plasma levels of three biomarkers - N-terminal pro-brain natriuretic peptide (NTproBNP), Troponin-T, and growth differentiation factor-15 (GDF-15) - in patients with paroxysmal AF (pAF) (≤7 days of continuous AF, n = 323) and persistent AF ((AF duration > 7 days and < 1 year, n = 84) using patients from AF RISK study (NCT01510210). In this AF-RISK sub-study, patients with persistent AF experienced more symptoms (higher European Heart Rhythm Association class (p < 0.001)), had a higher comorbidity burden (p < 0.001), and had more unfavorable echocardiographic parameters (p < 0.001). All three biomarker levels were significantly higher in patients with persistent AF as compared to those with pAF (p < 0.001). Multivariate linear regression analyses showed that age (beta-coefficient for NTproBNP: 0.21; GDF-15: 0.41; Troponin-T: 0.23) and CHA2DS2-VASc (beta-coefficient for NTproBNP: 0.20; GDF-15: 0.25; Troponin-T: 0.27) were determinants of all three biomarkers, and that persistent AF determined NTproBNP (beta-coefficient: 0.34), but not Troponin-T and GDF-15. More detailed analysis of CHA2DS2-VASc score showed that for all three biomarkers age, coronary artery disease and heart failure were determinants of plasma biomarkers levels, whereas sex determined NTproBNP and Troponin T, and hypertension determined NTproBNP and GDF15. Overall, this study therefore suggests that in AF, Troponin T and GDF15, and especially NTproBNP could be used to detect those patients with more persistent form of AF that may warrant more aggressive treatment of AF and concomitant comorbidities. Future studies, however, are essential to evaluate if more aggressive AF treatment and risk factor management will reduce disease progression and holds a novel therapeutic intervention to reduce the burden of AF.

Mitral prolapsing volume is associated with increased cardiac dimensions in patients with mitral annular disjunction.

INTRODUCTION: In patients with mitral annular disjunction (MAD), it can be difficult to assess the severity of mitral regurgitation (MR), as they present with a prolapsing volume (i.e. volume resulting from mitral valve prolapse, blood volume shift) rather than a regurgitant jet. The influence of the mitral prolapsing volume (MPV) on cardiac dimensions is unknown. We hypothesised that the severity of MR is underestimated in these patients. Our aim was to measure MPV and to investigate its influence on cardiac dimensions in patients with MAD. METHODS: We retrospectively included 131 consecutive patients with MAD from our institution's echocardiographic database. Transthoracic echocardiography was used to assess MPV. Additionally, we established a control group of 617 consecutive patients with degenerative mitral valve disease and performed propensity score matching. RESULTS: Median MPV in the MAD group was 12 ml. MPV was an independent predictor for left ventricular end-diastolic (LVEDD) and end-systolic diameter (LVESD) and left atrial volume (all p < 0.001). In patients with large prolapsing volumes (> 15 ml), LVEDD (56 ± 6 mm vs 51 ± 6 mm, p < 0.001), LVESD [38 mm (34-41) vs 34 mm (31-39), p < 0.01] and left atrial volume [105 ml (86-159) vs 101 ml (66-123), p = 0.04] were significantly increased compared to matched patients with degenerative mitral valve disease and similarly assessed severity of MR. CONCLUSION: Due to a volume shift based on the MPV rather than an actual regurgitant jet, MR severity cannot be assessed adequately in MAD patients. Increased MPV induces ventricular and atrial enlargement. These findings warrant future studies to focus on MPV as an additional parameter for assessment of the severity of MR in MAD patients.

Contemporary management of patients with atrial fibrillation in the Netherlands and Belgium: a report from the EORP-AF long-term general registry.

BACKGROUND: Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. METHODS: We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1­year follow-up data were gathered. RESULTS: At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). CONCLUSIONS: Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.

Gut-microbe derived TMAO and its association with more progressed forms of AF: Results from the AF-RISK study.

INTRODUCTION: The importance of gut microbiome in cardiovascular disease has been increasingly recognized. Trimethylamine N-oxide (TMAO) is a gut microbe-derived metabolite that is associated with cardiovascular disease, including atrial fibrillation (AF). The role of TMAO in clinical AF progression however remains unknown. METHODS AND RESULTS: In this study we measured TMAO and its precursor (betaine, choline, and L- carnitine) levels in 78 patients using plasma samples from patients that participated in the AF-RISK study. 56 patients suffered from paroxysmal AF and 22 had a short history of persistent AF. TMAO levels were significantly higher in patients with persistent AF, as compared to those with paroxysmal AF (median [IQR] 5.65 [4.7-9.6] m/z versus 4.31 [3.2-6.2] m/z, p < 0.05), while precursor levels did not differ. In univariate analysis, we observed that for every unit increase in TMAO, the odds for having persistent AF increased with 0.44 [0.14-0.73], p < 0.01. Conclusion: These results suggest that higher levels of TMAO are associated with more progressed forms of AF. We therefore hypothesize that increased TMAO levels may reflect disease progression in humans. Larger studies are required to validate these preliminary findings.Trial Registration number: Clinicaltrials.gov NCT01510210.

Determining the optimal interval for imaging surveillance of ascending aortic aneurysms.

BACKGROUND: Cardiovascular guidelines recommend (bi-)annual computed tomography (CT) or magnetic resonance imaging (MRI) for surveillance of the diameter of thoracic aortic aneurysms (TAAs). However, no previous study has demonstrated the necessity for this approach. The current study aims to provide patient-specific intervals for imaging follow-up of non-syndromic TAAs. METHODS: A total of 332 patients with non-syndromic ascending aortic aneurysms were followed over a median period of 6.7 years. Diameters were assessed using all available imaging techniques (echocardiography, CT and MRI). Growth rates were calculated from the differences between the first and last examinations. The diagnostic accuracy of follow-up protocols was calculated as the percentage of subjects requiring pre-emptive surgery in whom timely identification would have occurred. RESULTS: The mean growth rate in our population was 0.2 ± 0.4 mm/year. The highest recorded growth rate was 2.0 mm/year, while 40.6% of patients showed no diameter expansion during follow-up. Females exhibited significantly higher growth rates than men (0.3 ± 0.5 vs 0.2 ± 0.4 mm/year, p = 0.007). Conversely, a bicuspid aortic valve was not associated with more rapid aortic growth. The optimal imaging protocol comprises triennial imaging of aneurysms 40-49 mm in diameter and yearly imaging of those measuring 50-54 mm. This strategy is as accurate as annual follow-up, but reduces the number of imaging examinations by 29.9%. CONCLUSIONS: In our population of patients with non-syndromic TAAs, we found aneurysm growth rates to be lower than those previously reported. Yearly imaging does not lead to changes in the management of small aneurysms. Thus, lower imaging frequencies might be a good alternative approach.

Characteristics of patients with atrial fibrillation prescribed edoxaban in Belgium and the Netherlands: insights from the ETNA-AF-Europe study.

BACKGROUND: Studies on the use of non-vitamin K antagonist oral anticoagulants in unselected patients with atrial fibrillation (AF) show that clinical characteristics and dosing practices differ per region, but lack data on edoxaban. METHODS: With data from Edoxaban Treatment in routiNe clinical prActice for patients with AF in Europe (ETNA-AF-Europe), a large prospective observational study, we compared clinical characteristics (including the dose reduction criteria for edoxaban: creatinine clearance 15-50 ml/min, weight ≤60 kg, and/or use of strong p­glycoprotein inhibitors) of patients from Belgium and the Netherlands (BeNe) with those from other European countries (OEC). RESULTS: Of all 13,639 patients in ETNA-AF-Europe, 2579 were from BeNe. BeNe patients were younger than OEC patients (mean age: 72.3 vs 73.9 years), and had lower CHA2DS2-VASc (mean: 2.8 vs 3.2) and HAS-BLED scores (mean: 2.4 vs 2.6). Patients from BeNe less often had hypertension (61.6% vs 80.4%), and/or diabetes mellitus (17.3% vs 23.1%) than patients from OEC. Moreover, relatively fewer patients in BeNe were prescribed the reduced dose of 30 mg edoxaban (14.8%) than in OEC (25.4%). Overall, edoxaban was dosed according to label in 83.1% of patients. Yet, 30 mg edoxaban was prescribed in the absence of any dose reduction criteria in 36.9% of 30 mg users (5.5% of all patients) in BeNe compared with 35.5% (9.0% of all patients) in OEC. CONCLUSION: There were several notable differences between BeNe and OEC regarding clinical characteristics and dosing practices in patients prescribed edoxaban, which are relevant for the local implementation of dose evaluation and optimisation. TRIAL REGISTRATION: NCT02944019; Date of registration 24 October 2016.

Clinical determinants of early spontaneous conversion to sinus rhythm in patients with atrial fibrillation.

BACKGROUND: The current standard of care for acute atrial fibrillation (AF) focuses primarily on immediate restoration of sinus rhythm by cardioversion, although AF often terminates spontaneously. OBJECTIVE: To identify determinants of early spontaneous conversion (SCV) in patients presenting at the emergency department (ED) because of AF. METHODS: An observational study was performed of patients who visited the ED with documented AF between July 2014 and December 2016. The clinical characteristics and demographics of patients with and without SCV were compared. RESULTS: We enrolled 943 patients (age 69 ± 12 years, 47% female). SCV occurred within 3 h of presentation in 158 patients (16.8%). Logistic regression analysis showed that duration of AF <24 h [odds ratio (OR) 7.7, 95% confidence interval (CI) 3.5-17.2, p < 0.001], left atrial volume index <42 ml/m2 (OR 1.8, 95% CI 1.2-2.8, p = 0.010), symptoms of near-collapse at presentation (OR 2.4, 95% CI 1.2-5.1, p = 0.018), a lower body mass index (BMI) (OR 0.9, 95% CI 0.91-0.99, p = 0.028), a longer QTc time during AF (OR 1.01, 95% CI 1.0-1.02, p = 0.002) and first-detected AF (OR 2.5, 95% CI 1.6-3.9, p < 0.001) were independent determinants of early SCV. CONCLUSION: Early spontaneous conversion of acute AF occurs in almost one-sixth of admitted patients during a short initial observation in the ED. Spontaneous conversion is most likely to occur in patients with first-onset, short-duration AF episodes, lower BMI, and normal left atrial size.

Paradigm shifts in pathophysiology and management of atrial fibrillation-a tale of the RACE trials in the Netherlands.

In the past 20 years the Netherlands-based RACE trials have investigated important concepts in clinical atrial fibrillation (AF). Their scope ranged from rhythm versus rate control to early or delayed cardioversion and also included early comprehensive management of AF in two trials, one focusing on early 'upstream therapy' and risk factor management and the other on integrated chronic nurse-led care. Studies were mostly triggered by simple clinical observations including futility of electrical cardioversion in persistent AF; many patients with permanent AF tolerating day-after-day 'uncontrolled' resting heart rates of up till 110 beats/min; patients being threatened more by vascular risks than AF itself; and insufficient guideline-based treatments for AF. Also the observation that recent-onset atrial fibrillation generally converts spontaneously, obviating cardioversion, triggered one of the studies. The RACE trials shifted a number of paradigms and by that could change the AF guidelines. The initial 'shock-and-forget' attitude made place for increased attention for anticoagulation, and in turn, broader vascular risks were recognised. In a nutshell, the adage eventually became: 'look beyond the ECG, treat the patient'.

Catheter ablation in highly symptomatic Brugada patients: a Dutch case series.

AIMS: In the past few years, promising results were described in targeting the arrhythmogenic substrate of the epicardial right ventricular outflow tract (RVOT) region in patients with Brugada syndrome (BrS). In this report, we describe our experience with endo- and epicardial substrate mapping and ablation in a series of highly symptomatic BrS patients. METHODS: This case series consists of seven patients with clinical BrS diagnosis who underwent catheter ablation in two Dutch hospitals (Isala hospital Zwolle; and Amsterdam University Medical Centre, location AMC, Amsterdam) and Hamad Heart Hospital in Qatar between 2013 and 2017. All patients had an ICD and recurrent ventricular arrhythmia (VA) episodes. All patients underwent endo-and epicardial mapping of the RVOT region. Elimination of all abnormal potentials and disappearance of BrS ECG pattern during the ablation procedure was the aimed endpoint. RESULTS: The study group consisted of seven patients with mean age 45.6 ± 16.9 years. Five patients had SCN5A mutations. One patient was excluded from analysis, since ablation could not be performed due to a very large low-voltage area and was later diagnosed with arrhythmogenic right ventricular cardiomyopathy, associated with an SCN5A mutation. One patient underwent both endo- and epicardial ablation to eliminate VA. During a mean follow-up of 3.6 ± 1.5 years, 5/6 patients remained VA free with two patients continuing quinidine. CONCLUSION: In patients with BrS and drug-refractory VA, ablation of the arrhythmogenic substrate in the RVOT region was associated with excellent long-term VA-free survival. The majority of these highly symptomatic BrS patients had an SCN5A mutation and also low-voltage areas epicardially.

Idiopathic atrial fibrillation patients rapidly outgrow their low thromboembolic risk: a 10-year follow-up study.

BACKGROUND: Healthy atrial fibrillation (AF) patients will eventually outgrow their low thromboembolic risk. The purpose of this study is to compare the development of cardiovascular disease in healthy AF patients as compared to healthy sinus rhythm patients and to assess appropriate anticoagulation treatment. METHODS: Forty-one idiopathic paroxysmal AF patients (56 ± 10 years, 66% male) were compared with 45 healthy sinus rhythm patients. Patients were free of hypertension, antihypertensive and antiarrhythmic drugs, diabetes, congestive heart failure, coronary artery or peripheral vascular disease, previous stroke, thyroid, pulmonary and renal disease, and structural abnormalities on echocardiography. RESULTS: Baseline characteristics and echocardiographic parameters were the same in both groups. During 10.7 ± 1.6 years, cardiovascular disease and all-cause death developed significantly more often in AF patients as compared to controls (63% vs 31%, log rank p < 0.001). Even after the initial 5 years of follow-up, survival curves show divergent patterns (log rank p = 0.006). Mean duration to reach a CHA2DS2-VASc score > 1 among AF patients was 5.1 ± 3.0 years. Five of 24 (21%) patients with CHA2DS2-VASc > 1 did not receive oral anticoagulation therapy at follow-up. Mean duration of over- or undertreatment with oral anticoagulation in patients with CHA2DS2-VASc > 1 was 5 ± 3.0 years. CONCLUSION: The majority of recently diagnosed healthy AF patients develop cardiovascular diseases with a consequent change in thromboembolic risk profile within a short time frame. A comprehensive follow-up of this patient category is necessary to avoid over- and undertreatment with anticoagulants.

Review on Factors Influencing Physician Guideline Adherence in Cardiology.

Cardiovascular disease is the most common cause of death in Western countries. Physician adherence to guidelines is often suboptimal, resulting in impaired patient outcome and prognosis. Multiple studies have been conducted to evaluate patterns and the influencing factors of patient adherence, but little is known about factors influencing physician guideline adherence. This review aims to identify factors influencing physician guideline adherence relevant to cardiology and to provide insights and suggestions for future improvement. Physician adherence was measured as adherence to standard local medical practice and applicable guidelines. Female gender and older age had a negative effect on physician guideline adherence. In addition, independent of the type of heart disease, physicians without cardiologic specialization were linked to physician noncompliance. Also, guideline adherence in primary care centers was at a lower level compared with secondary or tertiary care centers. The importance of guideline adherence increases as patients age, and complex diseases and comorbidity arise. Appropriate resources and interventions, taking important factors for nonadherence in account, are necessary to improve guideline adoption and adherence in every level of the chain. This in turn should improve patient outcome.

Optimal long-term antithrombotic management of atrial fibrillation: life cycle management.

Optimal antithrombotic management of atrial fibrillation equals balancing between prevention of arterial thromboembolism, predominantly ischaemic stroke, and haemorrhagic complications. Over time different antithrombotic agents and strategies have been developed. At present, non-vitamin K antagonist oral anticoagulants (NOACs) are the first-line therapy for stroke prevention in patients with non-valvular atrial fibrillation (i.e. without a mechanical valve prosthesis or rheumatic heart disease). Considering the impact of the suboptimal adoption of recommended oral anticoagulant therapy, as experienced with the previous first-line vitamin K antagonists, this review focuses on adequate use of NOACs. As such, we address the most important and clinically challenging issues in the antithrombotic life cycle management for long-term stroke prevention in atrial fibrillation.

Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis.

Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in)stability; proteomic and metabolomics data are to be added to genetic information. 2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; disease mechanism-based biomarkers need to be identified; experimental systems are needed that incorporate whole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation. 3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences. 4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis à vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time. 5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novel modified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.

Stroke risk in patients with device-detected atrial high-rate episodes.

Cardiovascular implantable electronic devices (CIEDs) can detect atrial arrhythmias, i. e. atrial high-rate episodes (AHRE). The thrombo-embolic risk in patients showing AHRE appears to be lower than in patients with clinical atrial fibrillation (AF) and it is unclear whether the former will benefit from oral anticoagulants. Based on currently available evidence, it seems reasonable to consider antithrombotic therapy in patients without documented AF showing AHRE >24 hours and a CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes mellitus, prior stroke [doubled], vascular disease, age 65-74 years and female sex) ≥1, awaiting definite answers from ongoing randomised clinical trials. In patients with AHRE <24 hours, current literature does not support starting oral anticoagulation. In these patients, intensifying CIED read-outs can be considered to find progression in AHRE duration sooner, enhancing timely stroke prevention. The notion that AHRE and stroke coincide perseveres but should be abandoned since CIED data show a clear disconnect.

Real-life use of Rivaroxaban in the Netherlands: data from the Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation (XANTUS) registry.

BACKGROUND: The Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation (XANTUS) registry investigated the safety and efficacy of the factor Xa inhibitor rivaroxaban. We studied the Dutch XANTUS cohort to a ssess drug safety and prescription patterns in the Netherlands. METHODS: The XANTUS registry was designed as a European prospective, observational study among patients with non-valvular atrial fibrillation. Major bleeding and all-cause mortality were assessed every three months during a 1-year follow-up period. In this Dutch sub-cohort we were also specifically interested in dosing regimens and the incidence and reasons for temporary or permanent discontinuation. RESULTS: Patients (n = 899) had a mean age of 69 (SD ± 9) years and 64.8% were male. The median CHA2DS2-VASc score was 2 (IQR 2-4) and the median HAS-BLED score was 2 (IQR 1-2). Major bleeding occurred in 19 patients (2.4 per 100 patient-years) and 8 patients (1.0 per 100 patient-years) died during the 1­year follow-up period. According to renal function, label-discordant dosing was observed in 48 (8.3%) patients. Finally, 124 patients (13.8%) reported a temporary interruption of rivaroxaban treatment and 11.8% switched to another oral anticoagulant therapy after permanent discontinuation of rivaroxaban. CONCLUSION: In the Dutch subset of the XANTUS registry, we observed low rates of major bleeding and label-discordant dosing and high persistence rates during one year of follow-up in patients receiving rivaroxaban in routine clinical practice. However, documenting the motivation of novel oral anticoagulant (NOAC) type and dose is essential to study label-discordant prescription, a potential safety paradox and identify patient characteristics to optimise NOAC use and adherence.

Presence and extent of cardiac computed tomography angiography defined coronary artery disease in patients presenting with syncope.

BACKGROUND: In syncope patients, presence of coronary artery disease (CAD) is associated with poor prognosis. However, data concerning CAD prevalence in syncope patients without known cardiovascular disease are lacking. Therefore, the aim of this study was to investigate presence and extent of CAD in syncope patients. METHODS: We included 142 consecutive patients presenting with syncope at the outpatient cardiology clinic who underwent coronary computed tomography (CT) angiography. Syncope type was ascertained by two reviewers, blinded for coronary CT angiography results. Of the patients, 49 had cardiac syncope (arrhythmia or structural cardiopulmonary disease) and 93 had non-cardiac syncope (reflex [neurally-mediated], orthostatic or of unknown cause). Cardiac syncope patients were compared with matched stable chest pain patients regarding age, gender, smoking status, diabetes mellitus type 2 and systolic blood pressure. RESULTS: Distribution of CAD presence and extent in cardiac and non-cardiac syncope patients was as follows: 72% versus 48% any CAD; 31% versus 26% mild, 8% versus 14% moderate and 33% versus 7% severe CAD. Compared with non-cardiac syncope, patients with cardiac syncope had a significantly higher CAD presence and extent (p = 0.001). Coronary calcium score, segment involvement and stenosis score were also higher in cardiac syncope patients (p-values ≤0.004). Compared to the chest pain control group, patients with cardiac syncope showed a higher, however, non-significant, prevalence of any CAD (72% versus 63%) and severe CAD (33% versus 19%). CONCLUSION: Patients with cardiac syncope show a high presence and extent of CAD in contrast to non-cardiac syncope patients. These results suggest that CAD may play an important role in the occurrence of cardiac syncope.

Pathophysiology of idiopathic atrial fibrillation - prognostic and treatment implications.

The term idiopathic or lone atrial fibrillation (AF) is commonly used in the young and apparently healthy individual who suffers from AF. Although there is conflicting evidence concerning prognosis, these patients are at risk to develop (vascular) comorbidities in the years following AF onset. It is conceivable that early stages of vascular disease, undetectable by the routine diagnostics, may contribute to the pathophysiology of "apparently" idiopathic AF. At present, more advanced diagnostics have become available that can be deployed at low threshold in order to detect early stage or yet subclinical cardiovascular disease. In this respect one could raise the question whether idiopathic AF exists at all or that the arrhythmia acts as a harbinger of as yet undetected underlying vascular disease in this specific population. Assuming that idiopathic AF is the final arrhythmic expression of underlying genetic mutations and/or vascular diseases, high priority should be given to trace identifiable predisposing factors or the presence of early stages of underlying disease in order to treat these, or prevent their complications. A more comprehensive quest for potential hidden causes of idiopathic AF creates new therapeutic dilemmas, but also encourages further research regarding pathophysiology and new early treatment opportunities in patients with atrial fibrillation in general. The present review provides more insight regarding diverse pathophysiological mechanisms in the fundamental basis for idiopathic AF, outlines prognostic and treatment implications, and questions the robustness of its definition.

Lone or idiopathic atrial fibrillation, messenger of misery in sight.

This editorial refers to 'Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: a nationwide cohort study of 9519 patients' by T. Andersson et al. In order to adequately describe root causes and adverse consequences of apparently idiopathic AF, the requested study population has to be large and be followed for a very long time. Andersson et al. adequately deployed the excellent national Swedish health registries in order to cover the hiatus of aforementioned studies in the current idiopathic AF literature. Considering the notion that patients with idiopathic or lone AF have comparable prospects as AF patients overall but are only caught early in their 'arrhythmia and vascular career', the study by Andersson et al. should trigger physicians to give high priority to exposing predisposing factors or early stages of underlying cardiovascular disease in such a way that preventative measures can be accurately deployed in these patients.

Coronary artery-bronchial artery fistulas: report of two Dutch cases with a review of the literature.

BACKGROUND: Coronary bronchial artery fistulas (CBFs) are rare anomalies, which may be isolated or associated with other disorders. MATERIALS AND METHODS: Two adult patients with CBFs are described and a PubMed search was performed using the keywords "coronary bronchial artery fistulas" in the period from 2008 to 2013. RESULTS: Twenty-seven reviewed subjects resulting in a total of 31 fistulas were collected. Asymptomatic presentation was reported in 5 subjects (19 %), chest pain (n = 17) was frequently present followed by haemoptysis (n = 7) and dyspnoea (n = 5). Concomitant disorders were bronchiectasis (44 %), diabetes (33 %) and hypertension (28 %). Multimodality and single-modality diagnostic strategies were applied in 56 % and 44 %, respectively. The origin of the CBFs was the left circumflex artery in 61 %, the right coronary artery in 36 % and the left anterior descending artery in 3 %. Management was conservative (22 %), surgical ligation (11 %), percutaneous transcatheter embolisation (30 %), awaiting lung transplantation (7 %) or not reported (30 %). CONCLUSIONS: CBFs may remain clinically silent, or present with chest pain or haemoptysis. CBFs are commonly associated with bronchiectasis and usually require a multimodality approach to be diagnosed. Several treatment strategies are available. This report presents two adult cases with CBFs and a review of the literature.