Multibiomarker analysis in patients with acute myocardial infarction.

BACKGROUND: Novel biomarkers representing different pathobiological pathways and their role in patients with acute myocardial infarction (AMI) were studied. METHODS: We retrospectively analysed serum levels of soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR), heart-type fatty acid-binding protein (H-FABP) and plasma fetuin A in blood of patients with AMI (STEMI, n = 61; NSTEMI, n = 57) compared to controls with excluded coronary artery disease (n = 76). Furthermore, detailed correlation analysis was performed. RESULTS: Compared with controls, in patients with STEMI and NSTEMI higher levels expressed as median of sST2 in pg/mL (STEMI: 13210·9, NSTEMI: 11989·1, control: 5248; P < 0·001), GDF-15 in pg/mL (STEMI: 818·8, NSTEMI 677·5, control 548·6; P < 0·001), suPAR in pg/mL (STEMI: 3461·1, NSTEMI: 3466·7, control: 2463·6; P < 0·001), H-FABP in ng/mL (STEMI: 5·8, NSTEMI: 5·4, control: 0·0; P < 0·001) and lower plasma fetuin A levels in µg/mL (STEMI: 95, NSTEMI: 54, control: 116·6; P < 0·001) were detected. Correlation analysis found clinical and biochemical parameters such as ejection fraction, length of hospital stay, creatine kinase, NT-proBNP and hs Troponin T levels as well as inflammatory markers (CRP, leucocytes) to be significantly correlated with novel biomarkers. CONCLUSION: Plasma levels of novel biomarkers were significantly elevated (sST2, GDF-15, H-FABP, suPAR) or inversely downregulated (fetuin A) in patients with AMI compared to a control group with excluded coronary artery disease. Significant correlations with various clinical parameters and standard biochemical markers were found.

Impact of Moderate Altitude on Pro-Inflammatory Cytokines in Healthy Volunteers.

BACKGROUND: The induction of microvascular inflammation and the effects on cytokine production in blood due to hypoxia has been shown in the past. We have previously reported a statistically significant increase of the pro-inflammatory cytokine interleukin-8 (IL-8) in normobaric hypoxia in the setting of a hypoxia-chamber. In the present study, we sought to analyze plasma levels of inflammatory cytokines in a real-life stetting in order to foster our knowledge on hypoxia induced microvascular inflammation at moderate altitude. METHODS: Pro-inflammatory cytokines (IL-8, IL-6, TNF-α) were measured in an experimental field study, exposing 18 healthy volunteers to moderate hypoxia while staying at a mountain lodge in Diavolezza, Switzerland (2978 meters above sea level). Plasma cytokine levels were measured by ELISA. RESULTS: In contradiction to our results in a normobaric hypoxia-chamber, exposure to moderate hypoxia led to a significant decrease of plasma IL-8 levels in a real-life setting (from 2.902 (1.046 - 4.984) pg/mL to 1.395 (0.698 - 3.712) pg/mL, p = 0.034). Concentrations of IL-6 and TNF-α did not show statistically significant changes in comparison to baseline measurements. CONCLUSIONS: The results of this study show a decrease of proinflammatory cytokine IL-8 in a real life setting of moderate altitude in healthy individuals. Initiation of angiogenesis or subliminal stimulus for an altitude-induced inflammatory reaction may be explanations for this unexpected finding.

Coexistence of atrioventricular nodal reentrant tachycardia with other forms of arrhythmias.

OBJECTIVE: The aim of this retrospective study was to investigate the association of atrioventricular nodal reentrant tachycardia (AVNRT) with other forms of arrhythmia in individual patients and its consequences for treatment. SUBJECTS AND METHODS: This study comprised 493 consecutive patients aged 16-88 years (296 women and 197 men) who were diagnosed with a form of AVNRT via a standard 4-catheter electrophysiological study (EPS). Patients were clinically followed (range 0.5-12 years) at a single center. RESULTS: Coexistence of AVNRT with other types of tachycardias was observed in 197 (40%) patients. Atrial fibrillation was found most frequently in 94 (19%) patients as follows: focal atrial tachycardia, n = 40 (8%); atrial flutter, n = 32 (6%), and AV reentrant tachycardia, n = 22 (4%). Double tachycardia was present in 140 (30%) patients, and more than 2 different types of tachycardias were present in 57 (12%) patients. Transitions between AVNRT and other tachycardias occurred in 25 (5%) patients. Two or more tachycardias were ablated in 42 (9%) patients. The majority of patients were free of symptoms at the first follow-up, whereas 130 (26%) patients reported a variety of symptoms. CONCLUSION: Coexistence of AVNRT with other types of arrhythmias was a common finding among these patients. The most frequently observed double tachycardia was the combination of AVNRT with atrial tachyarrhythmias, such as atrial fibrillation, with a potential significance for further patient management.

High incidence of echocardiographic abnormalities of the interatrial septum in patients undergoing ablation for atrial fibrillation.

BACKGROUND: Atrial fibrosis or fatty deposition is known to increase the propensity for the development of atrial fibrillation (AF). Apart from the pulmonic veins, the interatrial septum (IAS) might play a role in the maintenance of AF. In contrast to left atrial anatomy and adjacent veins, the IAS cannot be visualized in detail with computed tomography. Thus, preprocedural transesophageal echocardiography (TEE) may provide important morphologic information beyond exclusion from atrial thrombi. METHODS: The study comprised 108 consecutive patients (mean age 60 ± 11 years; 98 men). AF was paroxysmal in 91 (84%) and persistent in 17 (16%) patients. We investigated the morphological characteristics of the IAS by TEE in patients who underwent radiofrequency ablation of AF. RESULTS: The IAS was structurally abnormal in 46 (43%) patients, showing the following echocardiograhic findings: atrial septal hypermobility or aneurysm (n = 27) associated with a patent foramen ovale (PFO) (n = 11) or with a small atrial septal defect (ASD) (n = 2), a septal flap associated with a PFO or an ASD (n = 8), and an abnormally thickened IAS (n = 12). A thrombus in the left atrial appendage was discovered in only 2 (2%) patients. CONCLUSIONS: A structurally abnormal IAS was diagnosed in nearly half of the patients undergoing ablation therapy for AF. The information obtained by TEE is mandatory to exclude left atrial thrombi prior the ablation procedure. Moreover, detailed knowledge of morphologic characteristics of the IAS facilitates an optimized and safe performance of the transseptal puncture using long sheaths with large diameters.

Case report: Short-long-short mechanism triggering sustained ventricular tachycardia in a patient with a single-chamber ICD but inhibiting antitachycardia therapy.

Introduction: Short-long-short (SLS) sequences are an important cause of ICD pro-arrhythmia and can initiate both polymorphic and monomorphic ventricular tachycardias (VT). Depending on the programming of a single-chamber ICD, the interplay between SLS sequences and combined VT detection criteria can be responsible for withholding adequate anti-tachycardia pacing (ATP) or shock therapy. Methods: A 78-year-old patient with ICD was admitted to our emergency department after external cardioversion of a long-lasting VT with hemodynamic compromise. The interrogation of the ICD revealed an SLS sequence initiating a monomorphic VT at a rate of 171 bpm (350 ms). The VT discrimination of the implanted single-chamber ICD was based on the onset and stability criteria as the patient had a history of paroxysmal atrial fibrillation. The ICD was programmed that both criteria had to be met for VT detection and initiation of anti-tachycardia therapy. Results: Due to the SLS sequence in combination with the programmed VT detection interval, the onset threshold was not fulfilled and inhibited adequate therapy. Some relatively slow VT beats following the SLS sequence resulted finally in a considerable delay in the declaration of the episode onset. As a first step, the threshold for VT detection was programmed to 150 instead of 160 bpm. To avoid SLS sequences and pause-dependent ventricular tachyarrhythmias, VVI backup stimulation was increased from 35 to 55 ppm. Besides, a device-specific algorithm called rate smoothing was activated as a potential preventive feature. On the 3-month follow-up, all sustained VT episodes were detected adequately by the reprogrammed device, resulting in appropriate anti-tachycardia pacing. After further refinement and less aggressive programming of rate smoothing, the patient remained free of symptoms and arrhythmias over a follow-up of more than 2.5 years, particularly since progression to permanent atrial fibrillation and pacing at a lower rate of 60 ppm. Conclusions: SLS sequences may initiate or trigger VT episodes. Misclassification of the true onset may occur in some ICD devices due to specific programming of VT detection criteria. If both criteria "Onset and Stability" have to be fulfilled, ICD therapy is not delivered despite ongoing VT. Anti-bradycardia backup pacing at a very low stimulation rate may facilitate SLS sequences in patients with ICD resembling a potential pro-arrhythmic mechanism. In case of gradual VT onset with some intervals slower than the programmed VT threshold, the detection rate has to be adjusted down to guarantee appropriate identification of the onset.

Emerging trends in cardiovascular research: HFpEF in the spotlight. A bibliometric analysis of the years 2009-2016.

INTRODUCTION: Up to 50% of patients suffering from acute decompensated heart failure show normal or slightly reduced left ventricular ejection fraction (LVEF). This syndrome, which is known as heart failure with preserved ejection fraction (HFpEF) is associated with increasing age. Epidemiological studies could portrait an increasing importance and an even emerging prevalence in the past decades. Still, there is currently no evidenced based medical treatment option available. Our aims were to identify upcoming trends and emerging concepts and to point out important centers in the global research of HFpEF. EVIDENCE ACQUISITION: We performed a bibliometric study on current science in the field of HFpEF to identify study characteristics, impact factors and the countries of origin of basic and clinical studies that were published within the years 2009 to 2016. We further prepared density equalizing maps for visualization of the obtained data. EVIDENCE SYNTHESIS: A total of 5413 studies was screened, of which 794 were found eligible. The scientific output in clinical studies rose from 25 in 2009 to 165 in 2016. Most of the publications had a clinical topic, followed by studies on new imaging techniques. Basic research trials were by far beyond. The USA, Japan and Germany were identified as the most important national contributors to global scientific output. CONCLUSIONS: This first bibliometric study in the field of HFpEF shows a substantial increase of research within the last decade, mainly in the USA, Japan, and continental Europe. As an ongoing therapeutic trend in this field, we identified RAAS-blockade and 5-phosphodiesterase-inhibition.

Delayed high-grade atrioventricular block requiring pacemaker implantation in a multiple sclerosis patient treated with fingolimod.

Fingolimod is a sphingosine-1-phosphate 1 (S1P1) modulator which retains lymphocytes in secondary lymphoid organs and is approved for the treatment of relapsing multiple sclerosis (MS). The decrease of heart rate and AV block are reversible side-effects of treatment initiation. We report a case of persistent high-grade atrioventricular (AV) block 450 days after start of fingolimod and permanent pacemaker requirement in late-onset relapsing multiple sclerosis (MS). We discuss emerging risk factors for cardiac conduction deficits including the recently discovered vagomimetic effects of S1P1 modulation, structural brain and spinal cord damage, ageing and comorbidities.

Safe application of extensive radiotherapy to a cardiac resynchronization device.

Patients with cardiac implantable electronic devices undergoing radiotherapy (RT) are prone to the risk of device failure. Guidelines and manufacturer's instructions are lacking practical recommendations for cumulative radiation doses to pacemakers or implantable cardioverter defibrillators. The present case demonstrates the effect of RT of a Merkel cell carcinoma near the location of a cardiac resynchronization therapy pacemaker. Despite guideline recommendations, surgical relocation or de novo implantation of the device on the contralateral side was avoided to prevent the dissemination of tumour cells, inflammation, and wound healing complications. A total dose of 47.25 Gy applied in very close proximity to the cardiac resynchronization therapy pacemaker was carried out safely without jeopardizing the patient and any device malfunction during and after treatment within >1.5 years of follow-up period. The present case demonstrates that high-dose RT near to a cardiac resynchronization therapy device can be carried out safely. Special precautions during RT as well as close device follow-up interrogations are mandatory. Large-scale studies are needed for the true frequency of adverse events.

Radial versus femoral access site for percutaneous coronary intervention in patients suffering acute myocardial infarction : A randomized prospective multicenter trial.

BACKGROUND: Transradial access (TRA) in percutaneous coronary intervention (PCI) is a widely used standard technique with lower complication rates compared to transfemoral access (TFA). The aim of this study was to evaluate the impact of TRA versus TFA for PCI on clinically significant vascular access complications in the setting of acute myocardial infarction (AMI). METHODS: This multicenter study randomly assigned 250 patients in a 1:1 fashion (TRA vs. TFA) admitted with or without ST-segment elevation AMI undergoing immediate PCI. The primary endpoint was defined as the occurrence of hematoma, pseudo-aneurysm or local bleeding at the access site requiring any further intervention and/or prolonged hospital stay. Radiation exposure to the patient and operator was also investigated. RESULTS: In the study cohort (N = 250 patients, mean age 62 ± 12.7 years, 76% males) 5 patients (2%) achieved the primary endpoint without a significant difference between groups, 4 out of 125 (3.2%) in the TFA group and 1 out of 125 (0.8%) in the TRA group (p = 0.17). Access site hematoma was significantly more frequent in the TFA group compared to the TRA group (24.8% vs. 8.8%, respectively; p < 0.0007). Local bleeding was only seen in the TFA group (3.2% vs. 0%, p = 0.04). Time intervals from admission to catheter laboratory to first balloon inflation were longer in the TRA compared to the TFA group (34 ± 17 min vs 29.5 ± 13 min, respectively; p = 0.018). Radiation exposure to the patient and operator was identical. CONCLUSION: The use of TRA was accompanied by lower rates of access site complications; however, the need for subsequent treatment or prolonged hospital stays was not observed using either of the two access approaches.

Spontaneous automaticity arising from a successfully ablated Mahaim fiber.

The authors describe a 22-year-old woman with regular and irregular arrhythmias exhibiting left bundle branch block (LBBB) morphology at various heart rates. An atriofascicular fiber was diagnosed as the underlying mechanism for the antidromic reciprocating tachycardia. In addition, spontaneous automaticity of the Mahaim fiber was present during electrophysiologic study. The accessory pathway was ablated successfully, targeting a Mahaim potential at the supero-anterior tricuspid valve annulus. Relatively slow automatic rhythms with identical LBBB morphology were recorded immediately after ablation, as well as during long-term follow-up in a more sporadic and subclinical form. Abnormal automaticity arising from the distal portions of the remnant pathway was considered to be the origin of the slow ventricular rhythms in this peculiar case.

Gender-specific effect of metabolic syndrome on rate adjusted QT interval in middle-aged participants of an atherosclerosis prevention program.

INTRODUCTION: The metabolic syndrome is a matter of immense public concern for atherosclerosis prevention. Key features are visceral obesity, dyslipidemia, hyperglycemia in the non-diabetic range, and arterial hypertension. Subclinical atherosclerosis is the clinical consequence of metabolic syndrome, which may influence the QT interval. The aim was to investigate the rate corrected QT interval in subjects with metabolic syndrome in comparison to those without cardiometabolic risk factor clusters, and to explore gender differences in cardiac repolarization between the two groups. PATIENTS, MATERIALS AND METHODS: Heart rate and QT interval were automatically measured from surface ECG in 1086 participants (767 men, 319 women) from the Salzburg-Atherosclerosis-Prevention-program-in-subjects-at-High-Individual-Risk (SAPHIR). To omit the QT adjustment bias inherent in Bazett's formula we used a QT adjustment method with linear scaling as described by Rautaharju. RESULTS: The prevalence of metabolic syndrome was 13.8% among males and 10% among females. Mean rate adjusted QT (QTa) intervals were longer in women than in men. Presence of metabolic syndrome, however, was associated with significantly prolonged QTa only in men but not in women. Adjustment for relevant confounders reduced the difference of mean QTa in men from 9.24 to 5.83 ms (95% CI 0.9-10.8), but this difference was still statistically significant (p = 0.021). The effect of metabolic syndrome on QTa was only partly mediated by hypertension and insulin resistance. In females, however, no relevant differences were detected for QTa interval between subjects categorized by presence or absence of metabolic syndrome. CONCLUSIONS: The findings indicate a significant association between metabolic syndrome and rate-invariant QT in middle-aged men after adjustment for other risk factors. QT measurement may provide additive diagnostic and prognostic information in populations undergoing cardiovascular risk screening. However, the effect of metabolic and hormonal factors on ventricular repolarization seems to differ between the sexes.

Lower body mass index and atrial fibrillation as independent predictors for mortality in patients with implantable cardioverter defibrillator.

AIM: To evaluate risk factors related to total mortality in an unselected population of patients implanted with a cardioverter defibrillator. METHODS: Survival analysis was performed retrospectively investigating the records of 77 consecutive patients implanted with defibrillators (median 67 years, range 38-83 years; 63 men). All patients were followed regularly in 3-month intervals. The cause of mortality was assessed clinically, including post-mortem examination of device to assess possible arrhythmogenic death. Predictors were assessed by Kaplan-Meier analysis with log-rank tests and by Cox regression analysis (proportional hazards). RESULTS: Defibrillator recipients had a mean (+/-standard deviation) ejection fraction of 34+/-13%, left ventricular end-diastolic dimension (LVEDD) of 6.24+/-0.8 cm, QRS duration of 129+/-34 ms, and body mass index (BMI) of 26.4+/-4.3 kg/m(2). Atrial fibrillation was present in 32 patients, paroxysmal fibrillation in 23, and permanent fibrillation in 9 patients. The estimate of mean survival time for all patients was 51.5 (95% confidence interval 46.6-56.5) months. During the study period 11/77 (14%) patients died. Mean follow-up time was 24.5 months (range 0.2-60.7) for survivors and 7.6 months (range 1.5-42) for non-survivors. Independent predictors of mortality were the NYHA class (P=0.004), BMI< or =26 kg/m(2) (P=0.024), presence of paroxysmal or permanent atrial fibrillation (P=0.014), and absence of arterial hypertension (P=0.010). LVEDD showed a weak significant effect on survival (P=0.049). CONCLUSION: Patients with implantable cardioverter defibrillator and a normal to lower BMI or atrial fibrillation had a significantly higher overall mortality. These factors may be indicative of end stage heart failure or diseases associated with high sympathetic activation.

Limited dose-effect relationship of adenosine for detection of atrioventricular nodal duality in patients with supraventricular tachycardias.

OBJECTIVE: The purpose of the study was to test the dose-effect relationship of adenosine for the diagnosis of dual atrioventricular (AV) nodal physiology in patients presenting with supraventricular tachycardia. SUBJECTS AND METHODS: The study population consisted of 57 patients (mean age 50 +/- 14 years; 36 females, 21 males) with palpitations related to supraventricular tachycardia. Adenosine was injected as bolus during sinus rhythm at rest in order to unmask dual AV nodal physiology by a PR jump on surface ECG (defined as a sudden increase by > or = 50 ms measured from the onset of the P-wave to the R-wave between two consecutive sinus beats). According to a stepwise clinical approach, adenosine was administered as bolus in incremental dosages (6 mg followed by 12 mg, if necessary up to 18 mg). Once a PR jump > or = 50 ms or a high-grade AV block was noted on surface ECG, the injection was stopped at that dose. RESULTS: A significant PR jump was noted after injection of 6 mg (n = 21, 99 +/- 30 ms) or 12 mg (n = 13, 94 +/- 35 ms), but not after 18 mg (n = 4, 35 +/- 10 ms) adenosine. Provocation of temporary first-grade AV block (n = 13) was associated with the longest increment of PR interval, whereas high-grade AV block (n = 36) produced a significantly shorter PR jump (105 +/- 35 vs. 65 +/- 40 ms, p = 0.0024). Electrophysiological study and ablation were performed in 37 highly symptomatic patients. AV nodal reentrant tachycardia was diagnosed in 33 patients and orthodromic AV reentrant tachycardia in 4 patients. CONCLUSION: The adenosine test was characterized by a reverse dose-effect relationship as far as identification of AV nodal duality was concerned.

High peak PaO2 values associated with adverse outcome in patients treated with noninvasive ventilation for acute cardiogenic pulmonary edema and pneumonia.

BACKGROUND: Noninvasive ventilation (NIV) has a sigificant impact on mortality in acute respiratory failure (ARF). Predictive parameters for mortality are of high interest. METHODS: We retrospectively analyzed 3759 blood gas analysis and clinical parameters of 475 patients presenting with ARF based on acute cardiogenic pulmonary edema and/or pneumonia. The influence of peak arterial oxygen partial pressure levels (PaO2) with respect to its predictive value for in-hopital and long-term mortality was investigated. RESULTS: Overall intra-hospital mortality was 24%. Peak PaO2 levels in kPa were significantly higher in non-survivors (20.01±10.11) compared to survivors (15.65±6.79, P<0.001). A univariate Cox proportional-hazards analysis for long-term mortality revealed associations with maximum PaO2 levels (overall cohort: HR= 1.02; 95% CI: 1.007-1.03; P=0.003; CPE: HR= 1.02; 95% CI: 0.99-1.04, P=0.05, pneumonia: HR= 1.02; 95% CI: 1-1.4, P=0.02). A PaO2 cut-off value of 13 kiloPascal (kPa) was calculated by means of Youden Index and remained true even after correction for APACHE 2 Score (HR= 1.50; 95% CI: 1.00-2.25; P=0.05) and for PaCO2 (HR= 1.63; 95% CI: 1.14-2.33; P=0.01). CONCLUSIONS: Peak PaO2 levels were associated with worse in-hopital and long-term mortality in patients treated with NIV due to ARF. These findings may indicate that application of high oxygen may be detrimental in such patients.

Elevated plasma levels of interleukin-16 in patients with acute myocardial infarction.

Interleukin (IL)-16, a polypeptide cytokine, plays a crucial role in the inflammatory process, acting as a chemoattractant for peripheral immune cells and has been linked to various inflammatory diseases. However, its role in patients with acute myocardial infarction (AMI) is unclear.We retrospectively analyzed serum levels of IL-16 in blood of patients with (STEMI, n = 45) and without ST-segment elevation myocardial infarction (NSTEMI, n = 42) compared with controls with excluded coronary artery disease (n = 55). Furthermore, correlation analysis with inflammatory cells, C-reactive protein (CRP) levels, dendritic cell precursors (DCPs), and other clinical and biochemical markers was performed.Compared with controls, patients with STEMI and NSTEMI evidenced higher levels of IL-16 in pg/mL (STEMI: 759.38 ±â€Š471.54, NSTEMI: 677.77 ±â€Š438.8, control: 500.45 ±â€Š432.21; P = .002). IL-16 correlated with CRP (r = 0.26, P = .001), leucocytes (r = 0.38, P < .001), NT-proBNP (r = 0.20, P = .02) and hsTnT (r = 0.25, P = .004). Circulating myeloid DCPs, plasmacytoid DCPs, and total DCPs showed a significant inverse correlation to IL-16 levels (r = -0.21, P = .01; r = -0.23, P = .005; r = -0.26, P = .002, respectively).Interleukin-16 might play an important role in the inflammatory process of patients suffering from AMI and correlates with inflammatory cell activation and clinical and biochemical markers. The cytokine IL-16 might upregulate the proinflammatory response and recruitment of inflammatory cells into infarcted myocardium.

A comparative analysis of novel cardiovascular biomarkers in patients with chronic heart failure.

BACKGROUND: Heart failure (HF) with reduced ejection fraction remains a major therapeutic challenge. The aim of this study was to investigate the role of novel cardiovascular biomarkers, i.e. soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) in patients with ischaemic (ICM) or dilative cardiomyopathy (DCM). MATERIALS AND METHODS: A total of 200 patients were enrolled in this study: 65 were diagnosed with DCM and 59 patients suffering from ICM were included. 76 patients without coronary artery disease or signs of heart failure were included as controls. Plasma samples of all patients were analyzed by use of ELISA. RESULTS: Levels of sST2, suPAR and H-FABP were significantly higher in ICM and DCM patients compared to the control group (p<0.0001). However, there were no significant differences between ICM and DCM in biomarker levels. Ejection fraction correlated inversely with cardiac biomarkers (sST2 p<0.0001, GDF-15 p=0.0394, suPAR p=0.0029, H-FABP p<0.0001). Similarly, CRP levels also showed a positive correlation with cardiac biomarkers. Renal insufficiency (p<0.0001) and diabetes (sST2 p=0.0021, GDF-15 p=0.0055, suPAR p=0.0339, H-FABP p=0.0010) were significantly associated with a rise in cardiac biomarkers. CONCLUSION: Novel cardiovascular biomarkers such as ST2, GDF-15, uPAR and H-FABP could offer a great potential for more precise diagnostic in ICM and DCM patients. H-FABP was the most promising marker in our study, followed by sST2, uPAR and GDF-15. Additional prospective studies will be necessary to further evaluate the potential clinical benefits in routine treatment of HF.

Association Between Vascular Cell Adhesion Molecule 1 and Atrial Fibrillation.

Importance: Accumulating evidence links inflammation and atrial fibrillation (AF). Objective: To assess whether markers of systemic and atrial inflammation are associated with incident AF in the general population. Design, Setting, and Participants: The Bruneck Study is a prospective, population-based cohort study with a 20-year follow-up (n = 909). The population included a random sample of the general community aged 40 to 79 years. Levels of 13 inflammation markers were measured at baseline in 1990. Findings were replicated in a case-control sample nested within the prospective Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study (n = 1770). Data analysis was performed from February to May 2016. Exposures: Levels of 13 inflammation markers. Main Outcomes and Measures: Incident AF over a 20-year follow-up period in the Bruneck Study. Results: Of the 909 participants included in the Bruneck Study, mean [SD] age was 58.8 (11.4) years and 448 (49.3%) were women. Among the 880 participants free of prevalent AF (n = 29) at baseline, 117 developed AF during the 20-year follow-up period (incidence rate, 8.2; 95% CI, 6.8-9.6 per 1000 person-years). The levels of soluble vascular cell adhesion molecule 1 (VCAM-1) and osteoprotegerin were significantly associated with incident AF (hazard ratio [HR], 1.49; 95% CI, 1.26-1.78; and 1.46; 95% CI, 1.25-1.69, respectively; P < .001 with Bonferroni correction for both), but osteoprotegerin lost significance after age and sex adjustment (HR, 1.05; 95% CI, 0.87-1.27; P > .99 with Bonferroni correction). Matrix metalloproteinase 9, metalloproteinase inhibitor 1, monocyte chemoattractant protein-1, P-selectin, fibrinogen, receptor activator of nuclear factor-κB ligand, high-sensitivity C-reactive protein, adiponectin, leptin, soluble intercellular adhesion molecule 1, and E-selectin all fell short of significance (after Bonferroni correction in unadjusted and age- and sex-adjusted analyses). The HR for a 1-SD higher soluble VCAM-1 level was 1.34 (95% CI, 1.11-1.62; Bonferroni-corrected P = .03) in a multivariable model. The association was of a dose-response type, at least as strong as that obtained for N-terminal pro-B-type natriuretic peptide (multivariable HR for a 1-SD higher N-terminal pro-B-type natriuretic peptide level, 1.15; 95% CI, 1.04-1.26), internally consistent in various subgroups, and successfully replicated in the SAPHIR Study (age- and sex-adjusted, and multivariable odds ratios for a 1-SD higher soluble VCAM-1 level, 1.91; 95% CI, 1.24-2.96, P = .003; and 2.59; 95% CI, 1.45-4.60; P = .001). Conclusions and Relevance: Levels of soluble VCAM-1, but not other inflammation markers, are significantly associated with new-onset AF in the general community. Future studies should address whether soluble VCAM-1 is capable of improving AF risk classification beyond the information provided by standard risk scores.