AbstractBackgroundAtrial Fibrillation Patients Research Articles

Assessing physicians’ knowledge, attitude, and practice on anticoagulant therapy in non-valvular atrial fibrillation: Syrian insights

BackgroundAtrial fibrillation (AF) is the most prevalent cardiac condition linked to increased mortality due to complications such as stroke. Oral anticoagulant (OAC) is the mainstay in preventing cerebrovascular accidents in patients with AF. Recent evidence identified gaps in physician’s knowledge in diagnosing and managing patients with AF. This study aims to assess Syrian physicians’ knowledge, attitude, and practices regarding the use of anticoagulant therapy in non-valvular AF (NVAF) patients. A cross-sectional study was conducted using a validated web-based questionnaire, which included 56 items separated into four sections that collected information about demographics, knowledge, attitude, and practices. Chi-square and Kruskal Wallis were performed to analyze the statistical relationships between the knowledge, attitude, practice, and demographic variables.ResultsA total of 497 participants completed the survey, of which 62.6% were between the ages of 25 and 35. The average participant scores for knowledge, attitude, and practices were (48.18 ± 21.57), (81.54 ± 9.26), and (62.83 ± 12.42), respectively. Participants who demonstrated good understanding, a positive attitude, and good practices were 22.3%, 87.3%, and 25.4%, respectively. The fear of bleeding was identified as the most significant barrier to initiating anticoagulant medication in AF patients (55.5%). Doctors who attended training had a better knowledge score than those who did not (mean ± S.D. = 57.24 ± 20.7). Participants who stated that over 70% of their AF patients use aspirin received the highest attitude score (mean ± S.D = 86.98 ± 21.17). PhD participants reported higher practice scores than those with other educational backgrounds (mean ± S.D = 73.96 ± 11.3).ConclusionThis research showed that primary care physicians in Syria had optimistic views regarding OAC therapy, suggesting that training interventions targeting physicians may lead to improvement in the treatment of patients with NVAF in Syria.

Risk differences between atrial fibrillation patients with different clinical phenotypes: insights from the French population

Abstract Background Atrial fibrillation (AF) patients represent a clinically complex, heterogeneous population comprising multiple homogeneous cohorts. Purpose We aimed to identify the common clinical phenotypes of AF patients and compare clinical outcomes between these subgroups. Methods A 1% representative sample of all AF patients hospitalized between 2010 and 2019 was identified from the French national database. Agglomerative hierarchical cluster analysis was performed using Ward’s method and squared Euclidian distance , to derive 4 distinct clusters of patients (Figure 1) using 31 clinical variables. Cox regression analyses were used to evaluate outcomes including all-cause death, cardiovascular death, non-cardiovascular death, ischaemic stroke, hospitalisation for heart failure (HF) and composite of ventricular tachycardia, ventricular fibrillation and cardiac arrest (VT/VF/CA). Results Four clusters were generated from the 12,688 patients included. Cluster 1 (n=2375) was younger, with a low risk of cardiovascular disease (CVD) and risk factors such as hypertension, dyslipidaemia and diabetes, but had the highest cancer prevalence. Clusters 2 (n=6441) and 3 (n=1639) depicted moderate-risk groups for CVD, with the female majority and high rates of lung conditions being the distinct features respectively. Cluster 3 also had the highest degree of frailty, with clusters 2 and 4 following closely. Cluster 4 (n=2233) represented a high-risk cohort for CVD with a high prevalence of coronary artery and vascular disease. Over a follow-up period of 2.0±2.3 years (median 1.1, interquartile range 0.1-3.4), cluster 3 had the highest cumulative incidence of all outcomes except for cardiovascular death which was highest in cluster 4. Compared to cluster 1, cluster 3 had the highest risk for all-cause death, HR 1.24 (1.09-1.41), cardiovascular death, HR 1.56 (1.19-2.06), non-cardiovascular death, HR 1.20 (1.04-1.38), hospitalisation for HF, HR 2.07 (1.71-2.50) and VT/VF/CA, HR 1.74 (1.20-2.53). Conclusion Four main clusters of AF patients were identified, discriminated by the differential presence of comorbidities. Our findings suggest that AF patients with moderate CVD-risk may have a poorer prognosis compared to AF patients with high CVD-risk in the presence of lung pathology. Therefore, this subgroup of patients may require more stringent management of existing comorbidities such as chronic obstructive pulmonary disease and sleep apnoea, alongside their AF.

The risk and cause of death according to prevalent atrial fibrillation and the role of CHA2DS2-VASc score to stratify the risk of all-cause and cardiovascular death

Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its prevalence is rapidly increasing. AF is associated with increased risks of stroke and all-cause death. Understanding the causes of death (COD), the relative risks of each cause in AF patients compared to non-AF population, and finding out modalities to stratify the risk of death among AF patients is essential to plan optimal care of AF patients. Purpose We aimed to analyze the COD of AF patients and the relative risk of death from specific causes in AF patients compared to non-AF population using a nationwide population based cohort. Also, we identified the role of CHA2DS2-VASc score to stratify the risk for all-cause death and death from cardiovascular causes in AF patients. Methods Using the Korean nationwide claims database, subjects who received nationwide health screening examination at 2009 and aged 40 or older were included (n=7,240,800). Patients with missing values in health examinations were excluded. Finally, 6,87,929 patients were included: 40,585 patients with AF and 6,837,344 subjects without AF. COD were classified by diagnostic codes. Results A total of 490,807 deaths were reported during follow-up (incidence rate of all-cause death: non-AF group, 19.1 and AF group, 34.2 per 1000 person-years). In AF group, cardiovascular diseases were the most common COD occupying 39.8% of all-death, whereas only 19% of non-AF subjects died due to cardiovascular diseases (Figure A). The proportion of death from cerebrovascular diseases in the AF group was two times higher than that of the non-AF group (15.1% vs. 7.5%, respectively). Compared to non-AF group, AF group was associated with a significantly higher risk of all-cause death (hazard ratio [HR] 1.739, 95% confidence interval [CI] 1.708-1.771, p <0.001) (Figure B). AF group was associated with higher risks of death from cardiovascular diseases and death from cerebrovascular diseases by almost 3-fold than non-AF group (HR [95% CI], 2.899 [2.814-2.985] for death from cardiovascular diseases; 2.899 [2.814-2.985] for death from cerebrovascular diseases, all p <0.001) (Figure B). Among AF patients, the risks of all-cause, cardiovascular, and cerebrovascular death were well-stratified by CHA2DS2-VASc scores (Figure C). The increases of HRs by increases of CHA2DS2-VASc score were more prominent in the risk of death from cerebrovascular diseases, followed by death from cardiovascular causes, and all-cause death. Conclusions Compared to non-AF subjects, AF patients showed higher risks of death from cardiovascular and cerebrovascular diseases. The risks of death from cardiovascular and cerebrovascular diseases were clearly stratified according to CHA2DS2-VASc score. Integrated management for AF patients should be focused on to prevent death from cardiovascular and cerebrovascular causes. CHA2DS2-VASc score could help to stratify the risk of all-cause death and death from specific causes in AF patients.

Kidney function by creatinine and cystatin c and adverse cardiovascular outcomes in patients with atrial fibrillation

Abstract Background Atrial fibrillation (AF) patients with chronic kidney disease are at an increased risk for ischemic and bleeding events and all-cause mortality. Accurate kidney function estimation is key for risk assessment. Creatinine is commonly used to calculate the Glomerular Filtration Rate (GFR). However, cystatin c has been described to be more sensitive than creatinine independent of muscle mass, autoimmune disease, inflammation or consuming diseases. Thus, cystatin C might be superior for risk assessment in patients with AF. Aim We aimed to investigate the associations between kidney function, assessed by creatinine and cystatin c, and major adverse cardiovascular events (MACE), its individual components, and major bleedings. Methods We enrolled 3865 AF patients into two prospective, multicenter cohort studies. Creatinine and cystatin c were measured at baseline and clinical outcome events were assessed yearly. We calculated GFR using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula based on either creatinine (GFRcr), cystatin c (GFRcy) or both (GFRc2). Primary outcome was MACE, defined as a composite of stroke or systemic embolism, myocardial infarction and cardiovascular death. Secondary outcomes were the individual components of MACE and major bleeding. Multivariable adjusted Cox regression analyses were built to investigate the associations between kidney function and adverse outcome events. Results Mean age was 71 ± 10 years and 28% were female. Mean creatinine and cystatin levels were 103 ± 32 μmol/l and 1.2 ± 0.4 mg/l, respectively, translating to a GFRc2 of 63.8 ± 21.7 ml/min/1.73 m2. Over a median follow-up of 6 years, the incidence rates for MACE (per 100 person-years) across quartiles (Q1-Q4) of GFRc2 were 22.0, 19.6, 17.4 and 15.9, respectively (Figure). When using multivariable adjusted Cox regression analysis, MACE was significantly associated with GFRcr (per 1 standard deviation: HR 0.87 (95%CI 0.77; 0.97) p=0.01), GFRcy (HR 0.68 (CI 0.58; 0.78), p<0.001) and GFRc2 (HR 0.75 (CI 0.66; 0.86), p<0.001). This association was mainly driven by cardiovascular death (Table). Major bleeding was associated with GFRcy (HR 0.73 (0.60-0.88) p=0.001) and GFRc2 (HR 0.80 (0.67-0.95), p=0.01), but not with GFRcr (HR 0.91 (95% CI 0.78-1.07) p=0.25). Conclusion Among AF patients, GFR equations including cystatin c were associated both with MACE and bleeding events, while creatinine based GFR equations were only associated with MACE. Therefore, Cystatin c based GFR equations might offer more comprehensive risk stratification in AF patients.Figure 1Table 1

Development of systematic care pathways to tackle multimorbidity in elderly patients with atrial fibrillation: results of a Delphi process among the Horizon 2020 EHRA-PATHS investigators

Abstract Background Atrial fibrillation (AF) is the result of underlying diseases and many underlying comorbidities impact clinical outcomes. Elderly AF patients (≥65 years) have on average five comorbidities. Comorbidity management requires a systematic approach and interdisciplinary care pathways, which are lacking in most care settings. The EHRA-PATHS H2020 project No. 945260, coordinated by EHRA and ESC, aims to tackle this problem. Purpose Searching consensus on the development of care pathways to systematically address multimorbidity in elderly patients with AF. Methods The EHRA-PATHS project comprises a consortium of 14 partners from 11 different European countries. Each partner comprised at least one other specialty besides cardiology, forming a multidisciplinary scientific team. Several steps were executed to develop care pathways for each comorbidity or risk factor, while guarding the overall feasibility of patient evaluation. (i) An extensive literature study identified the most common and relevant AF-related comorbidities. (ii) Groups of consortium partners created uniformly structured templates for each comorbidity care pathway through online meetings and discussions. (iii) A Two-Round Delphi study was performed to obtain consortium consensus on the final pathways, with experts reviewing the care pathway templates (for which they felt qualified). Templates with insufficient agreement (i.e. <80%) during Round 1 were adapted and presented during Round 2 for re-evaluation. The second Delphi Round was also used to rank/prioritize all the comorbidities for their impact on the clinical outcome of AF patients, and a grouping in those with mandatory vs. optional evaluation in AF patients. Results The literature study led to the initial identification of 22 different AF-related comorbidities, which was adjusted to 23 comorbidities after Delphi Round 1. The Delphi survey was sent to 37 experts from the consortium (Round 1: n=28 and Round 2: n=27 responses). After Round 1, 13 comorbidity templates had an agreement ≥80% and 9 comorbidities did not (Figure 1A). Based on these results, 12 comorbidities were included in Delphi Round 2 (since physical (in)activity and polypharmacy were added due to major adjustments, and osteoporosis was considered a separate comorbidity). After Round 2, 8 of these 12 comorbidity templates received an agreement ≥80% (Figure 1B). The final 4 comorbidity templates were finalized after further expert discussion. In the group of ‘mandatory’ comorbidities, hypertension, heart failure and overweight were seen as the most important ones. Sleep apnoea, low medication adherence and mild cognitive impairment, dementia, frailty were the top optional comorbidities. Conclusion A structured process of expert meetings and two Delphi Rounds led to the development and ranking of 23 care pathways to evaluate and manage comorbidities in AF patients. All pathways will now be combined and implemented into a decision support software system.Figure 1

Anticoagulation therapy in patients with atrial fibrillation and active cancer

Abstract Background Atrial fibrillation (AF) is common among cancer patients. Oral anticoagulation therapy (OAT) is important to prevent stroke in AF patients, but active cancer may also predispose to bleeding. Current knowledge on the use of OAT among AF patients with active cancer is scarce. Purpose To assess the influence of active cancer on the initiation of OAT in patients with AF and to explore cancer features predicting withholding OAT. Methods The nationwide FinACAF registry linked data from several registries covering all levels of care as well as drug purchases and included all 123 618 patients diagnosed with incident AF in Finland during 2011- 2018 with an indication for OAT (≥1 non-sex CHA2DS2-VASc point). Patients were considered to have active cancer if they had received a new cancer diagnosis or treatment for cancer during the preceding year from AF diagnosis. The primary outcome was the initiation of OAT (including non-vitamin K oral anticoagulants (NOAC) and warfarin) and the secondary outcome the initiation of any anticoagulation therapy (AAT; including OAT and low molecular-weight heparin) during the first year from AF diagnosis. Results The mean age of the patients was 73.9 (standard deviation 11.5) years and 62 955 (50.9%) of them were women. Altogether, 7015 (5.7%) patients had active cancer at AF diagnosis. The median CHA2DS2-VASc (3 [interquartile range 2-4] for both groups) and HAS-BLED (2 [interquartile range 2-3] for both groups) scores were similar in patients with active cancer and those without cancer history. Patients with active cancer, compared to those without cancer history, less often initiated OAT (47.7% vs. 70.5 %) or AAT (61.8% vs. 71.8%) (Figure). In Fine-Gray regression analyses with all-cause mortality as a competing risk, after adjusting for confounding factors, active cancer remained associated with lower likelihood of OAT (adjusted subdistribution hazard ratio (aSHR 0.501) (95% confidence interval (CI): 0.485-0.518), p<0.001) as well as AAT (aSHR 0.745 (95%-CI 0.723-0.769, p<0.001) initiation. Among cancer patients, metastases, gastrointestinal cancer and radiotherapy were associated with lower likelihood of OAT initiation, while only metastases predicted lower likelihood of AAT initiation (Table). Among patients initiating OAT, active cancer was associated with lesser likelihood of choosing a NOAC over warfarin compared to those without cancer (36.0% vs. 39.2%; adjusted hazard ratio 0.712 (95%-CI: 0.640-0.792), p<0.001). Conclusion AF patients with active cancer are less likely to initiate anticoagulation therapy, and those starting OAT are less likely to initiate with NOACs, compared to patients without cancer history. Metastases are the most important predictor of withholding anticoagulation therapy among AF patients with cancer.

Nationwide observational study of antithrombotic treatment strategies after coronary artery bypass graft surgery in patients with atrial fibrillation

Abstract Background Atrial fibrillation (AF) is common following coronary artery bypass graft surgery (CABG). Antiplatelet therapy (APT) is recommended after CABG to reduce graft failure. In the case of concomitant AF, this recommendation may instead include oral anticoagulation (OAC) guided by the CHA2DS2-VASc score and bleeding risk. Guidelines remain unclear on optimal antithrombotic treatment in AF patients after CABG. Purpose To assess comparative effectiveness and safety of different antithrombotic treatment strategies in AF patients after CABG. Methods In this nationwide observational study, we identified patients with AF in relation to isolated CABG surgery (before or ≤3 months after CABG) from January 2006 to January 2022 using national administrative registries. Patients alive and claiming a minimum of 1 antithrombotic prescription during the first 3 months after CABG were categorised in 1) APT alone, 2) OAC alone, and 3) OAC+APT. Incidence rates per 100 person-years were calculated for the effectiveness endpoint; a composite of all-cause mortality, stroke, and myocardial infarction, and its individual components, and for the safety endpoint; a composite of bleeding leading to hospitalisation. We also assessed the comparative effectiveness including its individual components and safety of APT and OAC+APT compared with OAC 3 to 12 months after CABG by multivariable Cox proportional-hazards models. Results We identified 33,763 patients who underwent CABG, of whom 6,008 (17.8%) patients had AF, were alive, and collected at least 1 antithrombotic drug ≤3 months after CABG. Temporal trends in the antithrombotic treatment strategies are illustrated in Figure 1. The mean age was 71 years, 18% were female, and 87% had a CHA2DS2-VASc score ≥2 for men and ≥3 for women. A total of 2,845 (47.3%) patients were treated with OAC+APT, 1,958 (32.6%) with APT alone, and 1,205 (20.1%) with OAC alone. Patients treated with APT more often had had a myocardial infarction and 87% had a CHA2DS2-VASc score ≥2 for men and ≥3 for women, whereas patients with OAC+APT more often had valve disease compared with OAC. The incidence rates per 100 patient-years (IR) of the effectiveness endpoint were 4.5 in patients with OAC+ACT, 4.8 with APT, and 4.9 with OAC. For the safety endpoint, the IR were 3.6 with OAC+ACT, 2.1 with APT, and 2.0 with OAC. No differences were found between treatment strategies for the effectiveness endpoint. Compared with patients with OAC, mortality was lower with OAC+APT (HR 0.66 [95% CI 0.45-0.98]) and APT (HR 0.53 [95% 0.34-0.84]), and bleeding risk was higher with OAC+APT (HR 1.69 [95% CI 1.08-2.64]) (Figure 2). Conclusion(s) Every third patient with AF were not treated with OAC after CABG. Compared with OAC alone, mortality was reduced in patients with OAC+APT and APT alone, and bleeding risk was higher in patients with OAC+APT. Future studies are warranted on optimal antithrombotic regimens in AF patients after CABG.Temporal trends in antithromboticsForest plot

Metabolomics and frailty: a "from bench to bedside" approach to atrial fibrillation in older patients

Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia diagnosed at an advanced age. The most important complications of AF are stroke, heart failure and dementia. The pathophysiology of the arrhythmia is complex and multifaceted and several aspects are still not completely understood. Purpose Our project aimed at exploring the molecular characteristics of AF in older patients using an untargeted metabolomics approach, an analytical technique that provides an insight of the global metabolic profile at an individual level. As secondary endpoints, we evaluated the association between metabolomics and acylcarnitines, which are mediators of myocyte electrical instability, and difference in metabolomics profile between healthy controls (C) and AF patients (AF-P). Method We evaluated 50 consecutive older AF-P with persistent AF, waiting to be treated with elective electrical cardioversion of the arrhythmia, and 22 healthy controls (C). In all patients, the cardiological evaluation was integrated with tools of the Geriatric Multidimensional Assessment (GMA) to describe neurocognitive function (Mini-Mental State Examination, MMSE), depressive symptoms (15-item Geriatric Depression Scale, GDS), and physical performance (Short Physical Performance Battery, SPPB). Interleukin-6 (IL-6), a marker of low-grade inflammation, was measured with ELISA assays. Metabolomics analysis and acylcarnitine measurements were carried out using gas chromatography coupled with mass spectrometry (GC-MS). Results AF-P and C did not differ by age (76 ± 6 vs. 70 ± 14 years, p = 0.055); patients had a lower proportion of women (AF-P: 32% vs. C: 64%, p = 0.012). Cluster analysis applied to metabolomic data in all population identified two subset of subjects, characterized by a different body mass index (BMI; 23.57 vs. 32.53 Kg/m², p = 0.046). When studying only the AF-P group, the simultaneous presence of a higher CHA2DS2-VASc score (4.17 ± 1.32 vs. 2.88 ± 1.83, p = 0.007), a lower physical function (SPPB; 8.97± 2.22 vs. 10.75 ± 1.13, p = 0.009), and higher IL-6 levels (4.42 vs. 2.39 pg/mL, p = 0.002) described the cluster with a worse clinical phenotype and a specific metabolomics pattern. Furthermore, an association between IL-6 and medium- long-chain acylcarnitines emerged (acylcarnitine 12:1, β = 31.7 ± 9.4, R = 0.446, p = 0.001). Conclusions Present analysis demonstrated that a specific metabolomics profile was characteristic of older AF patients with a frail phenotype, identified by higher CHA2DS2-VASc score and IL-6 concentration, and lower physical performance. Future studies are needed to reveal the single molecular pathways responsible of these behaviour, potentially useful to guide a targeted therapy. Last, inflammation per se could contribute to electrical instability in AF, while body mass index, a surrogate measure of undernutrition, could identify different metabolic pathways in controls and in patients with the arrhythmia.Metabolomics by clinical phenotypes

Factors associated with delayed treatment initiation of oral anticoagulants among Medicare patients with atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in the United States (US) and is associated with increased risk of stroke.1 Oral anticoagulants (OACs) are the primary treatment to reduce stroke risk in patients with AF.2,3 However, there is recent evidence of underuse of OAC in AF patients.4 Purpose To identify factors associated with delayed OAC treatment initiation among AF patients in the US clinical practice. Methods Medicare beneficiaries aged ≥65 years with a new diagnosis of AF without moderate-to-severe mitral stenosis or a mechanical heart valve after 1 Oct 2015 were included. Additional inclusion criteria included ≥1 claim for an OAC on or after 1st diagnosis of AF, ≥12 months of continuous Medicare Parts A, and D enrollment, and CHA2DS2-VASc score of ≥2 for males/≥3 for females. Time from 1st AF diagnosis to OAC initiation (index OAC), and demographic, sociodemographic, clinical and index OAC formulary characteristics were described. Delayed initiation was defined as OAC initiation >3 months after and early initiation as OAC initiation 0-3 months after 1st AF diagnosis. Factors associated with delayed OAC initiation were assessed using multivariable logistic regressions. Results A total of 446,441 patients met the inclusion criteria. Time from 1st AF diagnosis to OAC initiation was <1 month for 52.4% of patients, 1–≤3 months for 18.1%, >3–≤6 months for 7.1%, >6–≤12 months for 6.8%, and >12 months for 15.7%. Accordingly, 30% had delayed vs. 70% had early OAC initiation. Median age was 78 years (both), 48% and 47% were male, 87% and 89% were White, and median CHA2DS2-VASc score was 4 (both), respectively, for the delayed and early OAC initiation cohorts (Table 1). Factors associated with delayed OAC initiation included Black race (odds ratio [OR]: 1.29, 95% confidence interval [CI]: 1.25–1.33), South and West US census regions (OR: 1.22, 95%CI: 1.19–1.24 and OR: 1.29, 95%CI: 1.26–1.32, respectively), dementia (OR: 1.27, 95%CI: 1.23–1.30), congestive heart failure (OR: 1.20, 95%CI: 1.26–1.32), bleeding hospitalization ≤3 months before 1st AF diagnosis (OR: 1.22, 95%CI: 1.18–1.27), prior authorization (OR: 1.69, 95%CI: 1.66–1.71), and tier 4 formulary for index OAC at AF diagnosis (OR: 1.26, 95%CI: 1.22–1.30). Additionally, having low-income subsidy or dual eligibility (for Medicare and Medicaid) was associated with increased odds of delayed OAC initiation (OR: 1.06, 95%CI: 1.02–1.10 and OR: 1.09, 95%CI: 1.05–1.14, respectively; Figure 1). Conclusions In this study on Medicare patients with AF, Black race, low-income subsidy, and dual eligibility were found to be associated with delayed OAC initiation, suggesting potential disparities in the care of AF with timely OAC treatment. Moreover, OAC requiring prior authorization (the strongest predictor) or being on formulary tier 4 were associated with delayed initiation, indicating formulary restrictions may create barriers to timely OAC access for AF patients.Table 1.Patient characteristicsFigure 1.Factors of delayed initiation

Short and long-term renal function changes with direct oral anticoagulants in elderly patients with atrial fibrillation

Abstract Background Atrial Fibrillation (AF) and chronic kidney disease (CKD) frequently coexist in elderly patient. Previous evidence showed that vitamin K antagonists (VKAs) may be associated with an accelerated decrease of estimated glomerular filtration rate (eGFR) compared to direct oral anticoagulants (DOACs). However, there is little evidence on DOACs in the elderly population and in real life settings; the evidence available to us comes from randomized clinical trials with younger populations. Purpose The main objective of this study was to investigate the medium to long term renal function changes in older AF patients treated with DOACs and VKAs. Methods Enrolled patients underwent 3 eGFR measurements during follow-up, and the between arms difference in eGFR lost over time was investigated by 1) the Linear Mixed Models (LMM) and 2) group-based trajectory model (GBTM) analyses. Analysis was done according to short-term (3.2 years) and long-term follow-up (6.7 years). During the study period 420 enrolled AF patients (77.0±6.0 years, 136 on VKAs and 284 on DOACs) underwent 1260 eGFR assessments. Results After a median follow-up of 4.9 years, in the whole sample eGFR decreased from 67.4±18.2 ml/min/1.73 m2 to 47.1±14.3 ml/min/1.73 m2, p<0.001. Patients on DOACs experienced a significantly lower eGFR decrease that those treated with VKAs (-21.3% vs -45.1%, p<0.001). The benefit of DOACs compared with VKAs was evident both in the short term (eGFR decline -6.6 (95% CI: -9.1 to -4.0) ml/min/1.73 m2 vs -19.9 (95% CI: -23.6 to -16.2) ml/min/1.73 m2 respectively) and in the long-term, (eGFR -13.5 (95% CI: -16.1 to -11.0) ml/min/1.73 m2 in DOACs group vs -34.2 (95% CI: -37.9 to -30.5) ml/min/1.73 m2), respectively). After stratifying our study population into 5 groups according to trajectories of renal function decline, from the first (lowest decline in eGFR) to the fifth (greatest decline in eGFR), the first trajectory consisted of 80% patients on DOACs therapy. Logistic regression showed that the group on DOACs therapy was 3.03- to 4.24-fold more likely to belong to the trajectory with less eGFR decline than the VKAs group. Conclusions In conclusion, DOACs were associated with less long term decline in renal function in elderly patients with AF compared with VKAs.

Pulmonary hypertension is an adverse risk factor for patients admitted with atrial fibrillation

Abstract Background Atrial Fibrillation (AF) poses a significant burden on the resources of the American Healthcare system. Heart failure and AF commonly coexist in patients. Elevated left ventricular and atrial pressures result in progressive left atrial dilation and remodeling which in turn predisposes to the generation of AF. Many of these patients develop pulmonary hypertension (PHT) due to the remodeling and elevated left-sided pressures. Since many who have AF could have PHT, we aimed to assess outcomes in this population. Methods We utilized the National Inpatient Sample from 2016-2019 to identify roughly 16,500,000 hospitalized adults who had AF. These hospitalizations were further stratified based on the presence of PHT. A multivariate regression model was used to adjust for confounders and analyze the variables. Results Of those with AF, 1,855,020 (11.2%) had PHT. In-hospital mortality was higher in those with PHT (5.6% vs 4.9%; p<0.001). Figure 1 shows the Forrest plot for multivariate analysis of in-hospital outcomes when adjusted for patient demographics, comorbidities, and hospital characteristics. When adjusted similarly, patients with AF and PHT had longer length of stay (LOS) by 0.92 days (p<0.001) and had additional hospital costs (HC) of $9,463 (p<0.001). Conclusion In this study, patients admitted with AF with co-existing PHT had significantly worse outcomes in terms of in-hospital mortality, LOS, HC, cardiac arrest, pulmonary embolism, atrial flutter, AKI, blood transfusions, pneumonia, and endotracheal intubation. One major limitation of our study is the lack of outpatient follow up. Given that overall outcomes are worse in the setting of PHT, potential strategies for early rhythm control for AF should be pursued to avoid negative cardiac remodeling that would predispose to the development of PHT. AF patients with co-existing PHT should be aggressively monitored during hospitalizations as they have the potential to have worse outcomes.

Metabolomics to characterise adaptations in cellular metabolism for the stages of atrial fibrillation

Abstract Background Atrial fibrillation (AF) is a highly prevalent, progressive cardiac arrhythmia associated with high cardiovascular comorbidity. Current treatments targeting electropathophysiology have high recurrence rates, prompting researchers to uncover alternative molecular mechanisms underlying AF, aiming to find novel targets for diagnostics and treatment. Highly relevant to several cardiovascular diseases, adaptations in cellular metabolism have gained interest in AF. However, changes in the metabolome across various AF stages have not yet been studied. Aim The study aims to identify leads for potential biomarkers and treatment targets by gaining more insight in metabolic adaptation and mechanisms in atrial fibrillation. Methods From the HALT&REVERSE biobank, 60 atrial appendage samples were selected [controls (SR=21), paroxysmal (ParAF=16), persistent (PerAF=11) and longstanding-persistent AF (Ls-PerAF=12)]. Metabolomics, a large-scale semi-quantitative method based on mass-spectrometry, was performed. Comparisons were made SR vs. AF, and SR vs. AF stages by Mann-Whitney U and Kruskal Wallis statistical tests with a Benjamini-Hochberg correction (FDR=0,10) for multiple testing. Results Comparing SR and AF, fructose-1,6-diphosphate (F1,6DP) was decreased (p<0.001), whilst CDP (p<0.001) and UMP were increased (p<0.01). Comparing the AF stages, in SR vs. ParAF CDP was significantly increased. Regarding the AF stages, SR and LsperAF show the biggest differences in metabolites, presenting as decreases glycolysis and nicotinamide metabolites. Overall, metabolites associated with the glycolysis, nicotinamide, and carnitine metabolism show decreases in AF patients, whilst metabolites involved with pyrimidine metabolism are increased AF patients. Conclusion CDP, F1,6DP and UMP were strongly correlated with AF samples in univariate analyses and therefore should be further investigated in serum for their biomarker potential, specifically CDP which was already strongly increased in ParAF. F1,6DP and similar energy metabolites in the glycolysis and nicotinamide pathways are decreased in AF and therefore could be as a therapeutic target through supplementation. Leads from this analysis should be validated and further investigated in mechanistic studies of these metabolic pathways.

Mobile health technology integrated care in atrial fibrillation patients according to atrial fibrillation subtype: a subgroup analysis of the mAFA-II randomised trial

Abstract Background Atrial fibrillation (AF) is clinically categorised into different types (e.g. paroxysmal, persistent and permanent AF) according to the duration of the arrhythmia and whether it is accepted by physician and patient. These types of AF usually recognise different arrhythmic substrates, any may show different response to rate and rhythm control treatments. The Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) prospective cluster randomised trial proved the efficacy of a mobile health (mHealth) implemented ‘Atrial fibrillation Better Care’ (ABC) pathway (mAFA intervention) for the integrated care management of patients with AF. Whether the effect of mAFA intervention could differ between different types of AF is still unknown. Purpose To assess the efficacy of mAFA intervention according to the type of AF. Methods mAFA-II was a cluster randomised trial which recruited 3,324 adults AF patients between June 2018 and August 2019 in 40 centres in China. Clusters were randomised in a 1:1 ratio to mAFA intervention or usual care. In this analysis, we included patients with either paroxysmal, persistent or long-standing/permanent AF; we then assessed the interaction between these three types of AF and the effect of mAFA intervention on the risk of major outcomes using multivariable Cox regression analysis. Results were expressed as adjusted Hazard Ratio (aHR) and 95% Confidence Intervals (95%CI). The primary outcome was the composite of ischemic stroke/thromboembolism, all-cause death, and rehospitalizations. Results 2,489 AF patients were included in this analysis (mean age: 69.6±13.2, females 37.8%). Of these, 1,333 had paroxysmal AF (673 allocated to mAFA intervention), 828 had persistent AF (380 allocated to mAFA intervention), and 328 had long-standing/permanent AF (104 allocated to mAFA intervention). Patients with long-standing/permanent AF were older and more likely burdened by several comorbidities. On multivariable Cox regression analysis, the efficacy of the mAFA intervention on the risk of the primary composite outcome was similar in the three groups, without statistically significant interaction (p for interaction=0.337), with the highest effect seen among patients with persistent AF (aHR: 0.27, 95%CI: 0.11-0.66). Conclusions A mHealth-technology implemented ABC pathway showed a similar effect on the reduction of the primary composite outcome among patients with different subtype of AF. These findings support the implementation of integrated care approach also in patients with more advanced form of AF.Cox-regression models for interaction

The application of 4S atrial fibrillation scheme in predicting atrial arrhythmia recurrence after catheter ablation

Abstract Background Atrial fibrillation (AF) is the most common chronic cardiac arrhythmia. Recently, there is a new scoring system - 4S (Stroke Risk; Symptoms; Severity of Burden; Substrate), proposed in 2020 European Society of Cardiology AF guideline to identify the characteristics of AF patients in details and provide precise guidance for the AF management. Purpose We aimed to report the disease severity of AF patients who received first time catheter ablation (CA) using 4S-AF scoring system, and further discover the value of 4S-AF scheme in the prediction of atrial arrhythmia recurrence after CA. Methods We conducted a retrospective study of 350 AF patients between 2015 and 2017 referred for first time CA. The components of 4S-AF scheme including the following: (1) ischemic stroke risk (score 0 or 1), (2) symptoms (score 0 to 2), (3) severity of AF burden (score 0 to 2), (4) substrate (cardiovascular risk factors-score 0 to 2; left atrial enlargement-score 0 to 2). The 4S-AF score ranges from 0 to 9, and the study population was stratified into three groups as mild (score 0 to 2), moderate (score 3 to 4) and severe (score 5 to 9) disease. The 3-year risk of recurrence of atrial arrhythmias was studied using the Cox regression analysis. Atrial arrhythmias at follow-up were reported with a time-to-event analysis, and survival curves were created utilizing the Kaplan–Meier method with differences between groups compared with the log-rank test. Results The mean age of patients was 56 ± 11 years, 260 (74%) were men, and 82 (23%) had non-paroxysmal AF. Over the 3-year follow-up, 168 (47%) patients experienced recurrence. The recurrence rates were 32%, 47% and 62% for mild, moderate, and severe disease groups, respectively (Figure A). Non-paroxysmal AF (hazard ratios [HR]: 2.1, 95% confidence interval [CI]:1.5-2.9, p<0.001), larger left atrial dimensions (HR: 1.0, 95% CI:1.0-1.1, p=0.03) and a higher 4S-AF score (HR: 1.2, 95% CI:1.1-1.3, p=0.001) were significantly associated with a higher risk of recurrence of atrial arrhythmia. After the multivariate adjustment, a higher 4S-AF score (HR: 1.1, 95% CI:1.0-1.2, p=0.006) remained as the independent predictor of recurrence. The recurrence-free survival curves after CA are shown in Figure B. The severe disease group was associated with a 1.9-fold higher risk of atrial arrhythmia recurrence compared to mild disease group (HR 1.9, 95% CI:1.3-2.9, p =0.002). Conclusions The disease severity of AF patients characterized using 4S-AF scheme could predict the risk of atrial arrhythmia recurrence after CA.

Pulmonary hypertension is an adverse risk factor for peri-procedural complications in patients undergoing cardioversion for atrial fibrillation

Abstract Background Atrial Fibrillation (AF) poses a significant burden on the American Healthcare system. Heart failure and AF commonly coexist in patients. Elevated left ventricular and atrial pressures result in progressive left atrial dilation and remodeling which in turn predisposes to the generation of AF. Many of these patients develop pulmonary hypertension (PHT) due to the remodeling and elevated left-sided pressures. Cardioversion (CV) for non-valvular atrial fibrillation (AF) is commonplace for patients during their initial presentation. Since many who undergo CV for AF could have PHT, we aimed to assess the periprocedural outcomes in this population. Methods We utilized the National Inpatient Sample from 2016-2019 to identify roughly 330,820 hospitalized adults who had CV for AF. These hospitalizations were further stratified based on the presence of PHT. A multivariate regression model was used to adjust for confounders and analyze the variables. Results Of those who underwent CV for AF, 45,345 (13.7%) had PHT. In-hospital mortality was interestingly lower in those with PHT (9.6% vs 10.37%; p<0.001). Figure 1 shows the Forrest plot for multivariate analysis of in-hospital outcomes when adjusted for patient demographics, comorbidities, and hospital characteristics. When adjusted similarly, patients who underwent CV for AF and PHT had longer length of stay (LOS) by 2.11 days (p<0.001) and had additional hospital costs (HC) of $29,470 (p<0.001). Conclusion In this study, patients who underwent CV for AF with co-existing PHT had significantly worse outcomes in terms of LOS, HC, pulmonary embolism, atrial flutter, VT, SVT, AKI, and intubation. Of note, they interestingly had better outcomes in terms of in-hospital mortality, respiratory failure, and strokes. Returning the patient to sinus rhythm likely improved the left heart hemodynamics reducing post capillary pulmonary hypertension explaining the reduced mortality rate in this population. One major limitation of our study is the lack of outpatient follow up and the inability to differentiate between the different groups of PHT. Since several outcomes are worse in the setting of PHT, potential strategies for aggressive rate and volume control for those in AF should be pursued to avoid negative cardiac remodeling that would predispose to the development of PHT. AF patients with co-existing PHT should be aggressively monitored during hospitalizations as they have the potential to have worse outcomes.

Dementia risk among patients with atrial fibrillation treated with non-vitamin K vs. vitamin-K oral anticoagulants

Abstract Background Atrial fibrillation (AF) is associated with increased risk of dementia. Whether the use of direct oral anticoagulats (DOAC) is associated with lower risk of dementia compared to vitamin-K antagonist (VKA) is unclear. Purpose The purpose of this study was to assess the risk of new all-cause dementia and vascular dementia in AF patients, treated with either DOAC or VKAs. Methods Anonymized electronic medical records from the TriNetX federated research network were used. AF patients treated with DOACs within 1 month of AF diagnosis, were 1:1 propensity score- matched with those treated with a VKA. Patients were followed up to 10 years for all-cause dementia and vascular dementia. Logistic regression and Cox proportional hazard models were used to calculate odds ratios (OR) and hazard ratios (HR), respectively with 95% confidence intervals (CIs). Results Among 321,282 patients included in the propensity-scored cohort [mean (SD) age 69.7 (±13.5) years; 138,593 (43.1%) female], dementia was diagnosed among 15,050 (4.7%) patients. Among patients treated with DOACs, all-cause dementia was diagnosed in 6,337 (3.9%) and 8,713 (5.4%) among those treated with VKA (OR:0.72, 95%CI:0.69-0.74). Vascular dementia was diagnosed in 1,188 (0.7%) patients treated with DOACs and 1,766 (1.1%) among the VKA-treated (OR:0.67, 95%CI:0.62-0.72). DOACs were associated with lower risk of all-cause dementia and vascular dementia compared to VKA (HR:0.85, 95%CI:0.82-0.88 and HR:0.82, 95%CI:0.76-0.88, respectively). Conclusions In this large propensity-score matched analysis, AF patients treated with a DOACs had significantly lower risk of all-cause dementia and vascular dementia compared to those treated with VKA. This finding requires confirmation in ongoing randomised controlled trials.

Atrial fibrillation virtual ward - a hospital is not always the best place to be

Abstract Background Atrial fibrillation (AF) continues to represent a global health challenge. Our ability to prolong our lives has inevitably led to an increase in the incidence of AF, with subsequent increase in AF-related hospitalisations. With at least 92% of the global population having access to a digital telecommunication medium, virtual wards could be the way forward for managing acute AF patients. Purpose We implemented a virtual ward for hospital patients presenting with fast AF or atrial flutter (AFL), aiming to provide remote hospital-level care. Methods Patients presenting acutely with AF/AFL to the hospital were onboarded to the virtual ward and managed remotely at home, after being given access to a single-lead ECG device, a blood pressure monitor and pulse oximeter with instructions to record daily ECGs, blood pressure, oxygen saturations and to complete an online AF symptom questionnaire via a smartphone app. Data were uploaded to a digital platform for daily review by the clinical team. Admissions were either "step-up", where patients were onboarded to the virtual ward instead of hospitalisation, or "step-down" where early hospital discharge was facilitated through virtual ward support. Outcomes included hospitalisations avoided, bed-days saved and destination therapy plans (defined as electrical cardioversion, catheter ablation, or AV nodal ablation). Patients' satisfaction was assessed using the NHS Friends and Family test (FFT) and free-text narrative feedback. Results There were 118 virtual admissions between Jan 2022 – Jan 2023. Sixty-six (55%) of them avoided initial hospital admission as patients were directly enrolled to the virtual ward from outpatient settings. A further 61 re-admissions were appropriately prevented during virtual surveillance. Hence, avoiding a total of 127 unplanned hospitalisations, saving a median of 444 days (assuming a median hospital stay of 3.5 days per AF admission). The mean age on onboarding to the virtual ward was 66 ± 10 years. Mean HR at the time of onboarding and offboarding was 124 ± 22 and 84 ± 24 bpm respectively (P<0.0001; 95% CI= -47 to -34). A rhythm control strategy was pursued in 75% (n=88, P<0.0001), and 65% (n=75, P<0.0001) were referred for destination therapy. The FFT questionnaire yielded 100% positive responses among participants. Positive feedback themes focused on avoiding hospital stay and active participation in care plans, whilst the main negative comments addressed initial difficulty with technology and expressed the need for more instant communication. There were 5 unplanned discharges from the virtual ward requiring hospitalisation. Conclusion Our preliminary outcomes demonstrate a promising foundation for a reproducible model of healthcare delivery that provides an alternative to the traditional in-patient care for patients with AF. Thus, reducing the huge associated economic burden on healthcare without compromising on patients’ care or safety.AF virtual ward referral criteriaThe new Clinical Pathway

Association between blood pressure and new brain white matter lesions in atrial fibrillation patients

Abstract Background Atrial fibrillation (AF) and hypertension (HTN) often occur together. A cross-sectional study in patients with AF has shown that blood pressure (BP) is associated with white matter lesions (WML), which are known to have a negative impact on cognitive function. Purpose We aimed to investigate the association of BP and new WML occurring in patients with AF during a follow-up of 2 years. Methods We enrolled 1129 patients with documented AF who underwent a standardized brain magnetic resonance imaging (bMRI) at baseline and after 2-years follow-up. Systolic and diastolic blood pressure (SBP and DBP) were measured at baseline in every patient. BP was categorized into the following groups: optimal BP (SBP <120 mmHg and DBP <80 mmHg); normal BP (SBP ≥120 and <130 mmHg or DBP ≥80 and <85 mmHg); high normal BP (SBP ≥130 and <140 mmHg or DBP ≥85 and <90 mmHg); HTN grade 1 (SBP ≥140 and <160 mmHg or DBP ≥90 and <100 mmHg); HTN grade 2 and 3 (SBP ≥160 or DBP ≥100 mmHg). We defined new WML as new lesions or preexisting lesions with an increased volume after a 2-year follow-up period. We performed logistic and linear regression analyses to examine the relationship of BP, BP categories and the presence and volume of new WML. Additionally, interaction analyses were performed to evaluate the potential modifying effect of AF type (paroxysmal vs. non-paroxysmal) and heart rhythm (AF/atrial flutter vs. sinus rhythm). Results The mean ± standard deviation age was 71.5 ±8.4 years, 909 (74%) patients were male, and the mean BP was 135/79 ±18/12 mmHg. At baseline, WML were present in 98.9% of patients, with a median (interquartile range) volume of 3362 (1241 – 8650) mm³. The overall prevalence of new WML after 2 years was 18.8%, with a median volume of 108 (46.5 – 264) mm³. The prevalence of new WML stratified by BP categories is presented in Figure 1. After adjusting for multiple covariates, the presence of new WML was not significantly associated with BP categories or continuous SBP (Table 1). Compared to patients with optimal BP, the adjusted odds ratios (OR) (95% Confidence Intervals) were 1.40 (0.86 to 2.29) for normal BP; 1.13 (0.69 to 1.85) for high normal BP; 1.09 (0.69 to 1.76) for HTN grade 1; and 1.20 (0.67 to 2.11) for HTN grade 2 and 3 (p for linear trend 0.86). Per 10 mmHg increase in SBP, the adjusted OR was 0.97 (0.89 to 1.05, p= 0.46). Similarly, BP was not associated with volume of new WML. AF type and heart rhythm did not show any significant interaction effect for the association between SBP and presence of new WML (p-value for interaction of p=0.16 and p=0.57, respectively). Conclusions In a large cohort of AF patients, we found no association between BP and the presence and volume of new WML after a follow-up of 2 years. Long-term follow-up is warranted to determine the impact of BP on the development of new WML over time.

Myosin light chain dephosphorylation by ppp1r12c promotes atrial hypocontractility in atrial fibrillation

Abstract Background Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, increases thromboembolic stroke risk five-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C, the PP1 regulatory subunit targeting atrial myosin light chain 2 (MLC2a), causes hypophosphorylation of MLC2a and results in atrial hypocontractility. Methods Right atrial appendage tissues were isolated from human AF patients versus sinus rhythm (SR) controls. Western blots, co-immunoprecipitation, and phosphorylation studies were performed to examine how the PP1c-PPP1R12C interaction causes MLC2a de-phosphorylation. In vitro studies of pharmacologic MRCK inhibitor (BDP5290) in atrial HL-1 cells were performed to evaluate PP1 holoenzyme activity on MLC2a. Cardiac-specific lentiviral PPP1R12C overexpression was performed in mice to evaluate atrial remodeling with atrial cell shortening assays, echocardiography, and AF inducibility with EP studies. Results In human patients with AF, PPP1R12C expression was increased two-fold versus SR controls (P=0.02, n=12,12 in each group) with > 40% reduction in MLC2a phosphorylation (P=0.000001, n=12,12 in each group). PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF (P=0.03 and 0.007 respectively, n=8,8 in each group). In vitro studies utilizing drug BDP5290, which inhibits T560-PPP1R12C phosphorylation, demonstrated increased PPP1R12C binding with both PP1c and MLC2a, and dephosphorylation of MLC2a. Lenti-12C mice demonstrated a 150% increase in LA size versus controls (P=5.0x10-6, n=12,8,12), with reduced atrial strain and atrial ejection fraction. Pacing-induced AF in Lenti-12C mice was significantly higher than controls (P=0.02 and 0.04 respectively, n= 6,6,5). Conclusions AF patients exhibit increased levels of PPP1R12C protein compared to controls. PPP1R12C overexpression in mice increases PP1c targeting to MLC2a and causes MLC2a dephosphorylation, which reduces atrial contractility and increases AF inducibility. These findings suggest that PP1 regulation of sarcomere function at MLC2a is a key regulator of atrial contractility in AF.

Soluble ST2 biomarker utility in the comprehension of the clinical course of atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the more frequent arrhythmia in clinical practice and probably one of the more analyzed. Despite this, the clinical pattern classification not always correlates with the clinical course of AF. There are still a lack of biomarkers to predict recurrence and the clinical course of this disease. Purpose ST2 soluble (ST2S) biomarker has being previously analyzed by our group in patients with AF and electrical cardioversion (ECV) demonstrating utility to predict recurrence. We sought to analyze the clinical outcome of patients with AF who underwent an ECV or pulmonary vein isolation (PVI) and its correlation with the ST2S biomarker at mid-term follow-up. Methods We performed a prospective, observational clinical trial that included 250 patients with AF who were referred to our hospital for a clinical procedure including ECV or PVI from September 2016 to 2019. A total of 40 matched controlled patients were also included for the initial analysis. ST2S was analyzed from blood samples at baseline, 3- and 6-months follow-up. Results From 250 patients with AF: 94 underwent an ECV and 156 patients an PVI. Mean age was of 58.5 ±10.4 years. From the 156 PVI: 68 had paroxysmal and 88 persistent AF. Clinical follow-up was continued for 1 year and recurrence was of 65.9% in ECV and 22.4% in PVI patients. Clinical and echocardiographic characteristic are described in table1. The initial value of the ST2S biomarker was higher in AF cases with respect to controls (p<0.001). The patients with paroxysmal AF had higher levels of ST2S.0 (12113.4 pg/mL) respect to control cases but with no significant difference (p=0.234). Comparing the values of ST2S in persistent AF patients (15634.8 pg/mL) with controls the value was higher with a significant difference. ST2S baseline values were compared according to the rhythm and patients in AF had significantly higher levels with respect to those in sinus rhythm (SR). ST2S baseline values were also compared according to heart rate (HR) and those in tachycardia had higher levels respect to those who didn't(Table2). When analyzing ST2S levels in the complete cohort of patients with AF according to recurrence, there were no significant differences (Figure1). In multivariant analysis only AF rhythm and LA index volume were significant predictors of recurrence at 3 months follow-up and AF rhythm and age were predictors at 6 months follow-up. Conclusions ST2S baseline values were higher in persistent AF with respect to paroxysmal AF and only persistent AF patients had higher levels compared with controls. Initial ST2S biomarker levels did not have a predictive value in the global cohort of AF but do correlate with the type of AF and AF rhythm. With these results we consider that even though there is an association with AF and ST2S biomarker levels, when analyzing independently to the type of procedure ST2S values were not predictive of recurrence at mid-term follow-up.