Noninvasive Investigation of the Presence and Extent of Coronary Artery Disease by the Evaluation of Fingertip-Reactive Hyperemia.

OBJECTIVE: Fingertip-reactive hyperemia-peripheral artery tonometry (RH-PAT) is an emerging novel noninvasive method for evaluating endothelial function. We aimed to evaluate endothelial function with fingertip-reactive hyperemia by RH-PAT in symptomatic patients undergoing elective coronary angiography and to assess the relationship between the degree of endothelial dysfunction (ED) and the presence and the severity of coronary artery disease (CAD). SUBJECTS AND METHODS: We assessed 92 patients. Before coronary angiography, endothelial function was measured by RH-PAT and reactive hyperemia index (RHI) was obtained. For each patient, the Gensini score was calculated according to the coronary angiographic findings to evaluate the severity of CAD. RESULTS: In CAD (+) group, RHI (1.35 ± 0.57 vs. 1.74 ± 0.46, p = 0.001) mean values were lower than CAD (-) group. In multivariate logistic regression analysis, age, high-density lipoprotein, and RHI were found to be independent parameters predicting the presence of CAD. In multivariate linear regression analysis, RHI was found to be an independent predictor associated with the severity of CAD. In receiver operating characteristic curve analysis, RHI achieved an area under the curve of 0.763 (95% confidence interval 0.663-0.846, p = 0.001) for the ability to predict the presence of CAD. A cut-off value of 1.49 for an RHI predicted the presence of CAD with a sensitivity of 75% and a specificity of 72.9%. CONCLUSION: RH-PAT is an objective and highly reproducible test with superior diagnostic accuracy for the evaluation of ED. We found significant correlations between ED and the presence and the severity of CAD.

Echocardiographic assessment in cardiogenic shock.

Echocardiography is the most helpful diagnostic modality in cardiogenic shock, the management of which still remains challenging despite advances in therapeutic options. The presence of cardiogenic shock portends high mortality rates. Therefore, rapid recognition, identification of the underlying cause, and evaluation of the severity of hemodynamic dysfunction are vital for correct management. Whether the cause of shock is unknown, suspected, or established, echocardiography is utilized in its diagnosis and management as well as to monitor progress. It is recommended as the modality of first choice. No other investigative bedside tool can offer comparable diagnostic capability, allowing for exact targeting of the underlying cardiac and hemodynamic problems. Echocardiography can promptly provide an impression of the etiology of shock and the potential line of treatment. Normal left ventricular and right ventricular systolic function, normal cardiac chamber dimensions, absence of any significant valvular pathology, and absence of any pericardial effusion virtually rule out a cardiac cause of shock. This review discusses the role of echocardiography as a decision-making tool in the evaluation and management of cardiogenic shock.

Effects of angiotensin receptor neprilysin inhibition on P-wave dispersion in heart failure with reduced ejection fraction.

BACKGROUND: Angiotensin receptor neprilysin inhibitors (ARNI; sacubitril/valsartan combination) decrease morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). Increased P­wave duration and P­wave dispersion (Pd) reflect prolongation of atrial conduction and correlate with atrial fibrillation. Here, we aimed to assess the effects of switching from valsartan to ARNI treatment on the basis of P­wave indices. METHODS: A total of 28 patients with HFrEF (mean age, 64.8 ± 10.6 years; 18 males, 78.6% ischemic etiology) were included. All patients had New York Heart Association functional class II-III, left ventricular ejection fraction ≤35%, and had been switched from valsartan to ARNI treatment. Standard 12-lead electrocardiograms from patients on valsartan treatment and electrocardiograms 1 month after ARNI treatment were analyzed; heart rate, maximum P­wave duration (Pmax), minimum P­wave duration (Pmin), and Pd were calculated. Minnesota Living with Heart Failure Questionnaire (MLWHFQ) scores and N­terminal pro-brain natriuretic peptide (NT-proBNP) values were recorded. RESULTS: The Pmax (135.6 ± 32.1 ms vs. 116.1 ± 14.1 ms, p = 0.041) and Pd (33.6 ± 7.9 vs. 28.6 ± 5.3, p = 0.006) values were significantly reduced after ARNI treatment. Furthermore, ARNI treatment was associated with an improvement in MLWHFQ scores (31.2 ± 6.2 ms vs. 23.2 ± 7.0 ms, p < 0.001) and with a reduction in NT-proBNP values (1827.3 ± 1287.3 pg/ml vs. 1074.4 ± 692.3 pg/ml, p < 0.001). There were moderately positive correlations between the reduction in Pd and the improvement in MLWHFQ scores (r = 0.408, p = 0.031) and the reduction in NT-proBNP values (r = 0.499, p = 0.007) CONCLUSION: Switching to ARNI treatment alters Pd and Pmax favorably in patients with HFrEF. The reduction in atrial inhomogeneous conduction assessed by Pd was correlated with clinical improvement and reduced NT-proBNP levels in patients with HFrEF.

Evaluation of Erectile Dysfunction and Left Ventricular Diastolic Parameters in Lead Exposed Workers.

BACKGROUND: Lead exposure causes a wide range of vascular diseases through oxidative stress, sympathetic hyperactivity and impairment in nitric oxide bioavailability. In this study, the association between the effects of lead exposure on left ventricular diastolic indices and erectile function were assessed. METHODS: A total of 94 lead-exposed workers without known cardiovascular diseases or risk factors and 30 healthy subjects were enrolled. Systolic and diastolic functions were measured using transthoracic echocardiography. All participants were non-smokers. The International Index of Erectile Function Questionnaire (IIEF-5) was used to diagnose and grade erectile dysfunction (ED). Echocardiographic parameters, IIEF-5 score and blood lead level (BLL) were analyzed. RESULTS: The mean age and median BLL were 32.3 ± 6.4 years and 19 µg/dL in the workers, respectively. Sixty-five (69.1%) workers and 9 control subjects (30%) had ED. The IIEF-5 score was lower in the workers (17.0 ± 6.1) than in the controls (22.7 ± 2.1). In the workers, E and e' waves and E/A ratio were lower, and A wave, E/e' ratio, and left atrial volume index (LAVI) were higher than in the controls. Additionally, BLL was correlated with IIEF-5 score, e' wave, and E/e' ratio. IIEF-5 score was correlated with e' wave, E/e' ratio and LAVI. BLL was an independent risk factor for a decreased e' wave and IIEF-5 score and increased E/e' ratio in the lead-exposed workers. CONCLUSIONS: Impairment of diastolic and erectile functions, despite a younger age and in the absence of accompanying risk factors, was correlated with increased BLL.

Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF.

Fingertip Reactive Hyperemia Peripheral Arterial Tonometry Score Predicts Response to Biventricular Pacing.

PURPOSE: The objectives of this study were to: (i) evaluate endothelial function via fingertip reactive hyperemia peripheral arterial tonometry (RH-PAT) among heart failure (HF) patients receiving cardiac resynchronization therapy (CRT), (ii) assess the effects of CRT on RH-PAT score, and (iii) investigate whether RH-PAT score can identify CRT response. METHODS: A total of 63 patients (61.8 ± 10.3 years; 50 males; left ventricular (LV) ejection fraction 24.3 ± 3.9%) with HF who received CRT were enrolled. Endothelial function via RH-PAT was assessed 1 day before and 6 months after CRT. Minnesota Living with Heart Failure Questionnaire (MLWHFQ) was used to assess clinical improvements. CRT response was defined as a reduction in LV end-systolic volume ≥ 15% at 6 months. RESULTS: A RH-PAT score of < 1.7 signified a cut-off for endothelial dysfunction (ED). Baseline ED was observed among 43 (68.3%) patients and was more prevalent in responders (76.1% vs. 47.1%, p = 0.037). RH-PAT score improved 6 months after CRT (1.58 ± 0.35 vs. 1.71 ± 0.31, p = 0.012). A RH-PAT score of < 1.7 was a significant independent predictor of CRT response in multivariate logistic regression analysis (ß = 1.275, OR = 3.512, 95% CI = 1.231-11.477, p = 0.032). The severity of ED was an independent predictor of LV reverse remodeling (ß = -8.873, p = 0.015). Spearman's correlation analysis revealed moderate positive correlations between an improvement in RH-PAT (ΔRH-PAT) and LV reverse remodeling (r = 0.461, p = 0.001) and MLWHFQ score (r = 0.440, p = 0.001). CONCLUSIONS: ED detected via RH-PAT could predict the response to CRT. The RH-PAT score increased 6 months after CRT and was correlated with echocardiographic and clinical improvements.

Data mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial: 'exposing the invisible'.

AIMS: The aims of this study include (i) pursuing data-mining experiments on the Angiotensin II-Antagonist in Paroxysmal Atrial Fibrillation (ANTIPAF-AFNET 2) trial dataset containing atrial fibrillation (AF) burden scores of patients with many clinical parameters and (ii) revealing possible correlations between the estimated risk factors of AF and other clinical findings or measurements provided in the dataset. METHODS: Ranking Instances by Maximizing the Area under a Receiver Operating Characteristics (ROC) Curve (RIMARC) is used to determine the predictive weights (Pw) of baseline variables on the primary endpoint. Chi-square automatic interaction detector algorithm is performed for comparing the results of RIMARC. The primary endpoint of the ANTIPAF-AFNET 2 trial was the percentage of days with documented episodes of paroxysmal AF or with suspected persistent AF. RESULTS: By means of the RIMARC analysis algorithm, baseline SF-12 mental component score (Pw= 0.3597), age (Pw= 0.2865), blood urea nitrogen (BUN) (Pw= 0.2719), systolic blood pressure (Pw= 0.2240), and creatinine level (Pw= 0.1570) of the patients were found to be predictors of AF burden. Atrial fibrillation burden increases as baseline SF-12 mental component score gets lower; systolic blood pressure, BUN and creatinine levels become higher; and the patient gets older. The AF burden increased significantly at age >76. CONCLUSIONS: With the ANTIPAF-AFNET 2 dataset, the present data-mining analyses suggest that a baseline SF-12 mental component score, age, systolic blood pressure, BUN, and creatinine level of the patients are predictors of AF burden. Additional studies are necessary to understand the distinct kidney-specific pathophysiological pathways that contribute to AF burden.

Predictors of sinus rhythm after electrical cardioversion of atrial fibrillation: results from a data mining project on the Flec-SL trial data set.

AIMS: Data mining is the computational process to obtain information from a data set and transform it for further use. Herein, through data mining with supportive statistical analyses, we identified and consolidated variables of the Flecainide Short-Long (Flec-SL-AFNET 3) trial dataset that are associated with the primary outcome of the trial, recurrence of persistent atrial fibrillation (AF) or death. METHODS AND RESULTS: The 'Ranking Instances by Maximizing the Area under the ROC Curve' (RIMARC) algorithm was applied to build a classifier that can predict the primary outcome by using variables in the Flec-SL dataset. The primary outcome was time to persistent AF or death. The RIMARC algorithm calculated the predictive weights of each variable in the Flec-SL dataset for the primary outcome. Among the initial 21 parameters, 6 variables were identified by the RIMARC algorithm. In univariate Cox regression analysis of these variables, increased heart rate during AF and successful pharmacological conversion (PC) to sinus rhythm (SR) were found to be significant predictors. Multivariate Cox regression analysis revealed successful PC as the single relevant predictor of SR maintenance. The primary outcome risk was 3.14 times (95% CI:1.7-5.81) lower in those who had successful PC to SR than those who needed electrical cardioversion. CONCLUSIONS: Pharmacological conversion of persistent AF with flecainide without the need for electrical cardioversion is a powerful and independent predictor of maintenance of SR. A strategy of flecainide pretreatment for 48 h prior to planned electrical cardioversion may be a useful planning of a strategy of long-term rhythm control.

Demographics, treatment and outcomes of atrial fibrillation in a developing country: the population-based TuRkish Atrial Fibrillation (TRAF) cohort.

AIMS: Although atrial fibrillation (AF) is increasingly common in developed countries, there is limited information regarding its demographics, co-morbidities, treatments and outcomes in the developing countries. We present the profile of the TuRkish Atrial Fibrillation (TRAF) cohort which provides real-life data about prevalence, incidence, co-morbidities, treatment, healthcare utilization and outcomes associated with AF. METHODS AND RESULTS: The TRAF cohort was extracted from MEDULA, a health insurance database linking hospitals, general practitioners, pharmacies and outpatient clinics for almost 100% of the inhabitants of the country. The cohort includes 507 136 individuals with AF between 2008 and 2012 aged >18 years who survived the first 30 days following diagnosis. Of 507 136 subjects, there were 423 109 (83.4%) with non-valvular AF and 84 027 (16.6%) with valvular AF. The prevalence was 0.80% in non-valvular AF and 0.28% in valvular AF; in 2012 the incidence of non-valvular AF (0.17%) was higher than valvular AF (0.04%). All-cause mortality was 19.19% (97 368) and 11.47% (58 161) at 1-year after diagnosis of AF. There were 35 707 (7.04%) ischaemic stroke/TIA/thromboembolism at baseline and 34 871 (6.87%) during follow-up; 11 472 (2.26%) major haemorrhages at baseline and 10 183 (2.01%) during follow-up, and 44 116 (8.69%) hospitalizations during the follow-up. CONCLUSION: The TRAF cohort is the first population-based, whole-country cohort of AF epidemiology, quality of care and outcomes. It provides a unique opportunity to study the patterns, causes and impact of treatments on the incidence and outcomes of AF in a developing country.

Hypertension and cardiac arrhythmias: a consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE).

Hypertension is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease, stroke, peripheral artery disease and chronic renal insufficiency. Hypertensive heart disease can manifest as many cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both supraventricular and ventricular arrhythmias may occur in hypertensive patients, especially in those with left ventricular hypertrophy (LVH) or HF. Also, some of the antihypertensive drugs commonly used to reduce blood pressure, such as thiazide diuretics, may result in electrolyte abnormalities (e.g. hypokalaemia, hypomagnesemia), further contributing to arrhythmias, whereas effective control of blood pressure may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between hypertension and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit to comprehensively review the available evidence to publish a joint consensus document on hypertension and cardiac arrhythmias, and to provide up-to-date consensus recommendations for use in clinical practice. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and the patient in light of all of the circumstances presented by that patient.

A roadmap to improve the quality of atrial fibrillation management: proceedings from the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference.

At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients.

Unanswered Questions in Complex Fractionated Atrial Electrogram Ablation.

Pulmonary vein isolation has been accepted as potential target for ablation of paroxysmal atrial fibrillation (AF) given that the pulmonary veins are the main source of AF triggers. However, ablation strategies for persistent AF are less well defined. Mapping and ablation of complex fractionated atrial electrograms (CFAEs) is one strategy that has been proposed as a strategy for substrate modification although there is no consensus on their definition and procedural end points. Results of clinical studies have been conflicting. In this review, we aimed to discuss yesterday, today, and tomorrow of CFAEs ablation in persistent AF ablation.

Evaluating the Efficacy and Safety of Internal Cardioversion with Implantable Cardioverter Defibrillator Device for Atrial Fibrillation in Systolic Heart Failure Patients.

BACKGROUND: Atrial fibrillation (AF) commonly observed in patients with heart failure and cardioversion was often needed to restore the sinus rhythm. Previously, there is no study evaluating usefulness of internal cardioversion with implantable cardioverter defibrillator (ICD) device. In this study, we aimed to compare the efficacy and long-term effects of internal cardioversion with ICD devices compared to conventional external cardioversion in patients with AF and heart failure. METHODS: Seventy patients with AF and heart failure who underwent electrical cardioversion were enrolled in the study. Forty patients (mean age 65.36 ± 10.37, 35 male) were assigned to undergo internal cardioversion with approximately 35 J shocks delivered through the ICD electrode. Standard external cardioversion was performed for the remaining patients (30 patients; mean age 66.20 ± 11.89; 24 male) that were similar with regard to baseline, and electrocardiographic characteristics. RESULTS: Sinus rhythm was restored in 32 of 40 patients (80.0%) assigned to internal cardioversion compared with 25 of 30 patients (83.3%) assigned to external cardioversion (P = 0.725). We did not witness any serious complication during the procedure and hospitalization. On the follow-up, there was no statistically significant difference in recurrence of AF and incidence of major cardiovascular events between the internal and external cardioversion groups. CONCLUSIONS: Internal cardioversion with ICD device is an effective and safe method to restore sinus rhythm in heart failure patients with AF.

Prasugrel versus clopidogrel for acute coronary syndromes without revascularization.

BACKGROUND: The effect of intensified platelet inhibition for patients with unstable angina or myocardial infarction without ST-segment elevation who do not undergo revascularization has not been delineated. METHODS: In this double-blind, randomized trial, in a primary analysis involving 7243 patients under the age of 75 years receiving aspirin, we evaluated up to 30 months of treatment with prasugrel (10 mg daily) versus clopidogrel (75 mg daily). In a secondary analysis involving 2083 patients 75 years of age or older, we evaluated 5 mg of prasugrel versus 75 mg of clopidogrel. RESULTS: At a median follow-up of 17 months, the primary end point of death from cardiovascular causes, myocardial infarction, or stroke among patients under the age of 75 years occurred in 13.9% of the prasugrel group and 16.0% of the clopidogrel group (hazard ratio in the prasugrel group, 0.91; 95% confidence interval [CI], 0.79 to 1.05; P=0.21). Similar results were observed in the overall population. The prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of severe and intracranial bleeding were similar in the two groups in all age groups. There was no significant between-group difference in the frequency of nonhemorrhagic serious adverse events, except for a higher frequency of heart failure in the clopidogrel group. CONCLUSIONS: Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

A prospective DE-MRI study evaluating the role of TGF-ß1 in left atrial fibrosis and implications for outcomes of cryoballoon-based catheter ablation: new insights into primary fibrotic atriocardiomyopathy.

BACKGROUND: Transforming growth factor (TGF)-ß1 mediated atrial fibrosis plays a major role in the development of vulnerable atrial substrate for atrial fibrillation (AF). Although cryoablation effectively eliminates the triggers for AF, the impact of atrial substrate on the success of cryoablation remains unclear. OBJECTIVE: We aimed to investigate the association of plasma TGF-ß1 level with extent of left atrium (LA) fibrosis using delayed-enhanced magnetic resonance imaging (DE-MRI) and also effects of LA fibrosis on the success of cryoablation. METHODS: A total of 41 symptomatic lone paroxysmal AF patients (58.5% male; age: 49.2 ± 7.6 years) underwent initial cryoablation. Cardiac DE-MRI at 1.5-Tesla scanner to quantify atrial fibrosis, plasma TGF-ß1, clinical and echocardiographic data were collected before cryoablation. Postablation blanking period was observed for 3 months. RESULTS: DE-MRI revealed LA fibrosis in 27 (65.9%) patients with a median enhancement of 5% of the LA surface area. A total of 179 pulmonary veins (PV) were successfully isolated without any major complication. At median 18 months follow-up, 32 patients (78.1%) remained free of AF recurrence. Only plasma TGF-ß1 level (P = 0.001) was found to be the predictor of the extent of LA fibrosis. Multivariate Cox regression analysis pointed out that the extent of LA fibrosis (HR: 1.127, P = 0.007) and early AF recurrence (HR: 1.442, P = 0.011) were the independent predictors of AF recurrence in late follow-up. CONCLUSION: Higher levels of TGF-ß1 are associated with more extensive LA fibrosis and extent of LA fibrosis predict recurrences in patients undergoing cryoablation for lone AF.

The role of preprocedural monocyte-to-high-density lipoprotein ratio in prediction of atrial fibrillation recurrence after cryoballoon-based catheter ablation.

AIMS: Previous studies evidenced that increased monocyte count or activity and lower high-density lipoprotein (HDL) cholesterol levels were associated with more prevalent atrial fibrillation (AF) which attributed to pro-inflammatory and pro-oxidant effects. Monocyte-to-HDL ratio (M/H ratio) is a recently emerged indicator of inflammation and oxidative stress which have been only studied in patients with chronic kidney disease. We aimed to investigate the prognostic impact of M/H ratio on AF recurrence after cryoballoon-based catheter ablation. METHODS AND RESULTS: A total of 402 patients (43.5% female, age 53.5 ± 10.9 years, and 80.8% paroxysmal AF) with symptomatic AF underwent initial cryoablation procedure. Patients were categorized into quartiles on the basis of their pre-procedural M/H ratio. Post-ablation blanking period was observed for 3 months. At a mean follow-up of 20.6 ± 6.0 months, 95 patients (23.6%) had developed AF recurrence. Atrial fibrillation recurrence rates from the lowest to the highest M/H ratio quartiles were 7.4, 7.4, 16.8, and 68.4%, respectively (P < 0.001). On multivariate Cox regression analysis, the preablation M/H ratio (HR: 1.20, 95% CI: 1.15-1.25, P < 0.001), left atrial diameter, duration of AF history, and early AF recurrence were independent predictors of AF recurrence. Using a cut-off level of 11.48, the pre-ablation M/H ratio predicted AF recurrence during follow-up with a sensitivity of 85% and a specificity of 74%. CONCLUSION: Elevated pre-ablation M/H ratio was associated with an increased recurrence of AF after cryoballoon-based catheter ablation. Our results support the role of pre-ablation pro-inflammatory and pro-oxidant environment in AF recurrence after ablation therapy but suggest that other factors are also important.

Opportunities and challenges of current electrophysiology research: a plea to establish 'translational electrophysiology' curricula.

Cardiac electrophysiology has evolved into an important subspecialty in cardiovascular medicine. This is in part due to the significant advances made in our understanding and treatment of heart rhythm disorders following more than a century of scientific discoveries and research. More recently, the rapid development of technology in cellular electrophysiology, molecular biology, genetics, computer modelling, and imaging have led to the exponential growth of knowledge in basic cardiac electrophysiology. The paradigm of evidence-based medicine has led to a more comprehensive decision-making process and most likely to improved outcomes in many patients. However, implementing relevant basic research knowledge in a system of evidence-based medicine appears to be challenging. Furthermore, the current economic climate and the restricted nature of research funding call for improved efficiency of translation from basic discoveries to healthcare delivery. Here, we aim to (i) appraise the broad challenges of translational research in cardiac electrophysiology, (ii) highlight the need for improved strategies in the training of translational electrophysiologists, and (iii) discuss steps towards building a favourable translational research environment and culture.

The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results.

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this network.

Serum YKL-40 as a Marker of Left Atrial Fibrosis Assessed by Delayed Enhancement MRI in Lone Atrial Fibrillation.

BACKGROUND: Assessment of the left atrial (LA) fibrosis by using delayed-enhanced magnetic resonance imaging (DE-MRI) in atrial fibrillation (AF) patients is a pioneering noninvasive method. Serum YKL-40 is a novel marker for inflammation and known to play a role in ongoing tissue fibrosis. However, its role in LA fibrosis is unclear. We aimed to investigate the association of serum YKL-40 with the presence and extent of LA fibrosis. METHODS: A total of 50 patients with lone paroxysmal AF (62% male; age: 47.2 ± 7.0 years) underwent cardiac DE-MRI according to study protocol. Cardiac DE-MRI at 1.5 Tesla scanner was used to quantify LA fibrosis. Serum YKL-40 levels and clinical and echocardiographic data were recorded in all participants. RESULTS: DE-MRI revealed any degree of LA fibrosis in 31 (62%) patients. Median serum YKL-40 was significantly higher (P = 0.008) and left venticular ejection fraction was lower (P = 0.047) in patients with LA fibrosis as compared to patients without LA fibrosis. Extent of LA fibrosis was significantly correlated with age, duration of AF history, serum C-reactive protein, and serum YKL-40 levels. Only log (YKL-40) level was found as independent predictor for the presence of LA fibrosis (odds ratio: 1.626, P = 0.022). Multivariate linear regression analysis pointed out that duration of AF history (ß = 0.330, P = 0.003) and serum log (YKL-40) levels (ß = 0.546, P < 0.001) were significantly and independently associated with the extent of LA fibrosis. CONCLUSION: Higher levels of serum YKL-40 are associated with the presence and more extensive LA fibrosis in patients with lone AF. As a marker of inflammation, serum YKL-40 may also be used as an indicator for the degree of LA fibrosis.