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BACKGROUND: Cryoballoon (CB) versus radiofrequency (RF) ablation response on prothrombotic biomarkers obtained different results at short-term, while long-term is still unknown in atrial fibrillation (AF) treatment. We evaluated short and long-term changes in platelet and inflammatory biomarkers after CB and RF ablation. METHODS: Fifty-eight paroxysmal AF patients were randomized for pulmonary vein (PV) isolation using either CB (n = 29) or RF (n = 29) ablation. Biomarkers of platelet activation [P-selectin (CD62P), CD40 ligand (CD40L), platelet factor-4 (PF-4), mean platelet volume (MPV), platelet-leukocyte ratio (P-LCR), and platelet distribution width (PDW)]; and inflammatory [high sensitivity CRP (hs-CRP) and interleukin-6 (IL-6)] were measured at baseline, 18-24 h and 6-Months postablation. RESULTS: Twenty-four (86.2%) and twenty-six (89.7%) patients remained in sinus rhythm at 6-Months in CB and RF group respectively (p = 0.500). After 18-24 h postablation, CD62P, CD40L, PF-4, hs-CRP, and IL-6 levels were significantly activated in both groups (p 0.05) compared to baseline levels. hs-CRP and IL-6 levels were comparable between baseline and 6-Months in both groups (p > 0.05). CONCLUSIONS: CB ablation might influence the risk of thromboembolism due to less platelet activation after PV isolation and decreased platelet activation at long-term in maintained sinus rhythm patients compared to RF.

BACKGROUND: The occurrence of congestive heart failure (CHF) hospitalization among patients with atrial fibrillation (AF) is a poor prognostic marker. OBJECTIVE: The purpose of this study was to assess whether insulin-like growth factor-binding protein 7 (IGFBP-7), a marker of myocardial damage, identifies AF patients at high risk for this complication. METHODS: We analyzed 2 prospective multicenter observational cohort studies that included 3691 AF patients. Levels of IGFBP-7 and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured from frozen plasma samples at baseline. The primary endpoint was hospitalization for CHF. Multivariable adjusted Cox regression analyses were constructed. RESULTS: Mean patient age was 69 ± 12 years, 1028 (28%) were female, and 879 (24%) had a history of CHF. The incidence per 1000 patient-years across increasing IGFBP-7 quartiles was 7, 10, 32, and 85. The corresponding multivariable adjusted hazard ratios (aHRs) (95% confidence interval [CI]) were 1.0, 1.05 (0.63-1.77), 2.38 (1.50-3.79), and 4.37 (2.72-7.04) (P for trend

Objective Atrial fibrillation (AF) is the most common arrhythmia and associated with increased morbidity and mortality. Its increasing prevalence calls for novel biomarkers to identify underlying pathophysiological mechanisms as well as patients at risk. Methods Plasma samples from 1694 individuals from the Swedish population-based Malmö Preventive Project (mean age 69.5 years; 29.3% female; mean follow-up time 9.7±3.1 years) were analysed with the Olink proximity extension assay CVD III panel consisting of 92 proteins to identify proteins associated with incident AF or atrial flutter, referred to as incident AF. Incident cases of AF (n=278) were retrieved by linkage to the registers. Participants were followed until the first episode of AF or until censoring by death or emigration. Bonferroni-corrected multivariable Cox regression models adjusted for known risk factors were used to explore possible associations of the 92 proteins and incidence of AF. Results Multivariable Cox regression analyses of 11 proteins associated with incident AF (mean follow-up time 9.7±3.1 years) after Bonferroni correction confirmed N-terminal pro-B-type natriuretic peptide (HR per 1 SD increment (95% CI) 1.80 (1.58 to 2.04); p=1.2×10 -19) as risk marker of incident AF. Further, matrix metalloproteinase-2 (1.22 (1.07 to 1.39); p=0.002) and osteopontin (1.27 (1.12 to 1.44); p=2.7×10 -4) were associated with incident AF at follow-up independently of traditional risk markers and NT-proBNP. Conclusion In a general Swedish population, we confirmed the well-known association of NT-proBNP with incident AF and also identified matrix metalloproteinase-2 and osteopontin as novel risk markers for incident AF, independently of traditional risk factors and NT-proBNP.

Background:Dabigatran is prescribed to increasing numbers of patients with atrial fibrillation (AF). Although routine monitoring is not considered to be useful, measuring drug concentrations can be clinically relevant in specific situations. The aim of this study was the comparison of different functional and non-functional assays for determination of dabigatran concentrations at different timepoints in a real-life patient population with AF. We focused on the differences between assays in identifying patients with low drug concentrations. Furthermore, we studied the effect of glucuronidation on the established concentration as determined with different assays.Methods:This study established dabigatran concentration ranges in 40 real-life AF patients by an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) reference method and compared these with results from coagulation assays (Hemoclot dTT, LD-dTT and ECA). Samples were taken just before and 2 and 4 h after taking the drug.Results:A wide range of concentrations at different time points was found in this patient group. Coagulation assays correlate best with UPLC-MS/MS results that include the glucuronidated metabolites, showing that the pharmacologically active glucuronides are also measured in coagulation testing. The LD-dTT has the best agreement with UPLC-MS/MS and combines good sensitivity with high specificity. Several patients show consistently low or high drug concentrations, implying that drug exposure differs between patients.Conclusions:Based on the association of dabigatran concentrations with bleeding and thromboembolic risk, we believe that dabigatran monitoring could be beneficial for further optimizing anticoagulation therapy in AF.

Background: Both BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide) are widely used to aid diagnosis, assess the effect of therapy, and predict outcomes in heart failure and reduced ejection fraction. However, little is known about how these 2 peptides compare in heart failure and reduced ejection fraction, especially with contemporary assays. Both peptides were measured at screening in the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). Methods: Eligibility criteria in PARADIGM-HF included New York Heart Association functional class II to IV, left ventricular ejection fraction ≤40%, and elevated natriuretic peptides: BNP ≥150 pg/mL or NT-proBNP ≥600 pg/mL (for patients with HF hospitalization within 12 months, BNP ≥100 pg/mL or NT-proBNP ≥400 pg/mL). BNP and NT-proBNP were measured simultaneously at screening and only patients who fulfilled entry criteria for both natriuretic peptides were included in the present analysis. The BNP/NT-proBNP criteria were not different for patients in atrial fibrillation. Estimated glomerular filtration rate 2 was a key exclusion criterion. Results: The median baseline concentration of NT-proBNP was 2067 (Q1, Q3: 1217–4003) and BNP 318 (Q1, Q3: 207–559), and the ratio, calculated from the raw data, was ≈6.25:1. This ratio varied considerably according to rhythm (atrial fibrillation 8.03:1; no atrial fibrillation 5.75:1) and with age, renal function, and body mass index but not with left ventricular ejection fraction. Each peptide was similarly predictive of death (all-cause, cardiovascular, sudden and pump failure) and heart failure hospitalization, for example, cardiovascular death: BNP hazard ratio, 1.41 (95% CI, 1.33–1.49) per 1 SD increase, P P Conclusions: The ratio of NT-proBNP to BNP in heart failure and reduced ejection fraction appears to be greater than generally appreciated, differs between patients with and without atrial fibrillation, and increases substantially with increasing age and decreasing renal function. These findings are important for comparison of natriuretic peptide concentrations in heart failure and reduced ejection fraction.

Objectives. To examine the long-term risk of thromboembolism and bleeding in patients with atrial fibrillation comparing patients with and without recent breast cancer in subgroups with or without anticoagulation therapy, respectively. Design. Using nationwide registries, patients with breast cancer from 1998–2015 and subsequent atrial fibrillation within 3 years were stratified on anticoagulation and matched 1:3 on age, sex and comorbidities with atrial fibrillation patients without breast cancer. Risks of thromboembolism and bleeding were estimated by Aalen-Johansen and multivariable cox regression models. Results. Atrial fibrillation patients with and without anticoagulation were matched, respectively (201 and 525 with breast cancer matched with 603 and 1,575 without breast cancer). In patients with CHA2DS2-VASc-score >1 and anticoagulation the three years risks of thromboembolism were 4.2% (95% confidence interval (CI) 1.1–7.3) and 3.2% (CI 1.5–4.9) in patients with and without breast cancer. The risks of bleeding were 5.3% (CI 1.7–8.9) and 5.1% (CI 3.0–7.1), respectively. Breast cancer was associated with a similar risk of thromboembolism in patients with and without anticoagulation, respectively (Hazard ratio (HR) 1.10, CI 0.63–1.92 and HR 1.11, CI 0.82–1.50) and a similar risk of bleeding in patients with and without anticoagulation, respectively (HR 1.01, CI 0.56–1.84 and HR 0.85, CI 0.57–1.27) compared with the matched controls. Conclusions. Breast cancer was not associated with altered risk of thromboembolism or bleeding in patients with atrial fibrillation irrespective of treatment with anticoagulation. Our analyses suggest that atrial fibrillation diagnosed in patients with breast cancer should be considered as primary atrial fibrillation.

High-sensitivity C-reactive protein (hs-CRP) is a marker for the risk of cardiovascular and overall mortality. However, information about the association between hs-CRP and mortality in patients with atrial fibrillation is scarce. A total of 293 participants of the Atherosclerosis Risk In Communities study with a history of AF and hs-CRP levels available were studied. During a median follow-up of 9.4 years, 134 participants died (46%). The hazard ratio of all-cause mortality associated with the highest versus the lowest tertile of hs-CRP was 2.52 (95% confidence interval 1.49 to 4.25) after adjusting for age, gender, history of cardiovascular diseases, and cardiovascular risk factors. A similar trend was observed for cardiovascular mortality (57 events; hazard ratio 1.90, 95% confidence interval 0.81 to 4.45). The Congestive heart failure, Hypertension, Age >75 years, Diabetes, and previous Stroke or transient ischemic attack (CHADS2) score was also associated with all-cause and cardiovascular mortality, with an adjusted hazard ratio of 3.39 (95% confidence interval 1.91 to 6.01) and 8.71 (95% confidence interval 2.98 to 25.47), respectively, comparing those with a CHADS2 score >2 versus a CHADS2 score of 0. Adding hs-CRP to a predictive model including the CHADS2 score was associated with an improvement of the C-statistic for total mortality (from 0.627 to 0.677) and for cardiovascular mortality (from 0.700 to 0.718). In conclusion, high levels of hs-CRP constitute an independent marker for the risk of mortality in patients with atrial fibrillation.

MATERIALS AND METHODS: A total of 179 patients with atrial fibrillation in stable anticoagulant treatment were included. Thirty-two had a previous ischemic stroke. We measured thrombin generation, plasma concentrations of fibrinogen and C-reactive protein and analysed fibrin structure and lysability by turbidity. Fibrinolytic capacity was measured using the euglobulin fraction of plasma expressed in terms of t-PA equivalents (IU/ml).RESULTS: The patients with previous stroke had a slightly higher burden of co-morbidities compared with the remaining patients as indicated by the CHA2DS2-VASc score, but no significant differences were found regarding age, fibrinogen concentration, C-reactive protein, thrombin generation or fibrinolytic capacity. Furthermore, the patients with previous stroke had a higher mass/length ratio of fibrin fibers (5.5 vs. 5.1 x10(12) Da/cm, p=0.044) and an increased lysability (79.3 vs. 55.3%, pCONCLUSION: The higher lysability of fibrin clots in atrial fibrillation patients with previous stroke is most likely a result of a difference in fibrin fiber properties. An increased lysability may increase the risk of embolization of clots formed in the atria, and therefore fibrin clot structure seems to be a determinant of stroke risk in atrial fibrillation.INTRODUCTION: Atrial fibrillation increases the risk of ischemic stroke, but the risk depends on other factors as well. Present risk stratification schemes use age and co-morbidities, but not biochemical markers. We investigated the hypothesis that the formation, structure and lysability of fibrin clots are potential determinants of stroke risk in patients with atrial fibrillation.