Changes in right ventricular dimensions, function, and pulmonary circulation loading according to the degree of interdialytic weight gain in maintenance hemodialysis patients.

INTRODUCTION: The aim of this study was to investigate changes in echocardiographic right ventricular (RV) indices in relation to the degree of fluid accumulation between hemodialysis sessions, evaluated according to the recommended threshold of interdialytic-weight-gain corrected for dry weight (IDWG%). METHODS: A post-hoc analysis was performed using data from 41 maintenance hemodialysis patients. Patients were divided into a higher (>4.5%) and a lower (<4.5%) IDWG% group and underwent an echocardiographic assessment at the start and the end of the 3-day and the 2-day interdialytic interval. RESULTS: RV systolic pressure (RVSP) increments were more pronounced in the higher compared to the lower IDWG% group (16.43 ± 5.37 vs. 14.11 ± 13.38 mm Hg respectively, p = 0.015) over the 3-day interval, while changes in RV filling pressures, did not differ significantly between the groups (p = 0.84). CONCLUSIONS: During the 3-day interdialytic interval, pulmonary circulation is particularly overloaded in patients with fluid accumulation higher than the recommended thresholds, as evidenced by higher RVSP elevations.

Use of apixaban in adults with congenital heart disease and atrial arrhythmias: The PROTECT-AR study.

BACKGROUND: Adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) face an increased risk of thromboembolic events. Limited data exist on the use of non-vitamin K oral anticoagulants for thromboprophylaxis in ACHD. We aimed to assess the effectiveness and safety of apixaban in ACHD patients with AA. METHODS: PROTECT-AR (NCT03854149) was a prospective, multicenter, observational study conducted from 2019 to 2023. ACHD patients with atrial fibrillation, atrial flutter, or intra-atrial re-entrant tachycardia on routine apixaban treatment were included. The historical control group consisted of patients previously on vitamin K antagonist (VKA), who were analyzed prior to their transition to apixaban. The primary effectiveness endpoint was the composite of stroke or thromboembolism. The primary safety endpoint was major bleeding. RESULTS: The study enrolled 218 ACHD patients with AA on apixaban, of which 73 were previous VKA users. The analysis covered 527 patient-years of prospective exposure to apixaban and 169 patient-years of retrospective exposure to VKA. The annualized rate of stroke or thromboembolism was 0.6% in the apixaban group and 1.8% in the VKA group (absolute difference - 1.2%; upper limit of one-sided 95% confidence interval [CI] 0.9%, lower than the predefined non-inferiority margin of +1.8%, Pnon-inferiority < 0.001). The annualized rate of major bleeding was 1.5% in the apixaban group and 2.4% in the VKA group (hazard ratio 0.64; 95% CI 0.19-2.10, P = 0.48). CONCLUSION: In ACHD patients with AA, routine apixaban use exhibited a non-inferior rate of stroke or thromboembolism compared to historical VKA use, alongside a similar rate of major bleeding.

Serum prolactin levels and mortality in adults without prolactinoma: A meta-analysis.

PURPOSE: Prolactin is a highly versatile, multifunctional hormone synthesized and secreted by lactotroph cells of the anterior pituitary. Its metabolic role has been extensively studied even in normoprolactinemic populations. Recently, a wealth of observational data outlines the potential prognostic value of prolactin in various clinical settings. This systematic review aims to systematically evaluate and quantitatively synthesize the association between serum prolactin levels and risk of mortality in adults without prolactinoma. METHODS: A systematic literature search was conducted up to June 10, 2023 to identify studies reporting the association of serum prolactin levels with clinical outcomes of adults without prolactinoma. A random-effects meta-analysis was conducted to quantify the adjusted hazard ratios [(a)HRs] for all-cause and cardiovascular death during follow-up. RESULTS: Twenty-eight studies were deemed eligible reporting the outcomes of adults without prolactinoma, in whom serum prolactin levels were measured for risk-stratification. Fourteen studies reported appropriate data for meta-analysis encompassing a total of 23,596 individuals. Each unit of prolactin increase was independently associated with increased risk of all-cause (pooled aHR=1.17 [1.08-1.27]; I2=48%) and cardiovascular mortality (pooled aHR=1.54 [1.14-2.09]; I2=89%). Individuals belonging to the highest prolactin category had significantly higher risk for all-cause (pooled aHR=1.81 [1.43-2.30]; I2=65%) and cardiovascular (pooled aHR=1.59 [1.04-2.42]; I2=82%) mortality compared to their lowest prolactin category counterparts. The association between prolactin levels and in-hospital death did not reach statistical significance. CONCLUSIONS: Prolactin levels seem to be an independent predictor for mortality. Further validation is warranted before its role as a risk stratification tool can be delineated in clinical practice.

Atrial Fibrillation Ablation in Congenital Heart Disease: Therapeutic Challenges and Future Perspectives.

The increasing prevalence of atrial fibrillation (AF) in adults with congenital heart disease raises significant questions regarding its management. The unique underlying anatomic and physiological background further adds to the difficulty in eliminating the AF burden in these patients. Herein, we provide an overview of the current knowledge on the pathophysiology and risk factors for AF in adult congenital heart disease, with a special focus on the existing challenges in AF ablation. Emerging imaging modalities and ablation techniques might have a role to play. Evidence regarding the safety and efficacy of AF ablation in adult congenital heart disease is summarized, especially for patients with an atrial septal defect, Ebstein anomaly of the tricuspid valve, tetralogy of Fallot, and Fontan circulation. Finally, any remaining gaps in knowledge and potential areas of future research are highlighted.

Residual leaks following percutaneous left atrial appendage occlusion and outcomes: a meta-analysis.

BACKGROUND AND AIMS: Residual leaks are not infrequent after left atrial appendage occlusion. However, there is still uncertainty regarding their prognostic implications. The aim of this study is to evaluate the impact of residual leaks after left atrial appendage occlusion. METHODS: A literature search was conducted until 19 February 2023. Residual leaks comprised peri-device leaks (PDLs) on transoesophageal echocardiography (TEE) or computed tomography (CT), as well as left atrial appendage patency on CT. Random-effects meta-analyses were performed to assess the clinical impact of residual leaks. RESULTS: Overall 48 eligible studies (44 non-randomized/observational and 4 randomized studies) including 61 666 patients with atrial fibrillation who underwent left atrial appendage occlusion were analysed. Peri-device leak by TEE was present in 26.1% of patients. Computed tomography-based left atrial appendage patency and PDL were present in 54.9% and 57.3% of patients, respectively. Transoesophageal echocardiography-based PDL (i.e. any reported PDL regardless of its size) was significantly associated with a higher risk of thromboembolism [pooled odds ratio (pOR) 2.04, 95% confidence interval (CI): 1.52-2.74], all-cause mortality (pOR 1.16, 95% CI: 1.08-1.24), and major bleeding (pOR 1.12, 95% CI: 1.03-1.22), compared with no reported PDL. A positive graded association between PDL size and risk of thromboembolism was noted across TEE cut-offs. For any PDL of >0, >1, >3, and >5 mm, the pORs for thromboembolism were 1.82 (95% CI: 1.35-2.47), 2.13 (95% CI: 1.04-4.35), 4.14 (95% CI: 2.07-8.27), and 4.44 (95% CI: 2.09-9.43), respectively, compared with either no PDL or PDL smaller than each cut-off. Neither left atrial appendage patency, nor PDL by CT was associated with thromboembolism (pOR 1.45 and 1.04, 95% CI: 0.84-2.50 and 0.52-2.07, respectively). CONCLUSIONS: Peri-device leak detected by TEE was associated with adverse events, primarily thromboembolism. Residual leaks detected by CT were more frequent but lacked prognostic significance.

Prognostic implications of thyroid disease in patients with atrial fibrillation.

Atrial fibrillation (AF) is often accompanied by thyroid disease (THD). This study aimed to explore the relationship between THD and the occurrence of significant clinical outcomes in patients with AF. This post hoc analysis utilized data from the MISOAC-AF trial (NCT02941978), which enrolled hospitalized patients with AF. Patients were categorized based on their THD history into hyperthyroidism, hypothyroidism, or euthyroidism. Cox regression models were employed to calculate unadjusted and adjusted hazard ratios (aHRs). The primary outcomes of interest included all-cause mortality, cardiovascular death, and hospitalizations during the follow-up period. The study included 496 AF patients (mean age 73.09 ± 11.10 years) with available THD data, who were followed-up for a median duration of 31 months. Among them, 16 patients (3.2%) had hyperthyroidism, 141 (28.4%) had hypothyroidism, and 339 (68.4%) had no thyroid disease. Patients with hypothyroidism exhibited higher rates of hospitalization during follow-up (aHR: 1.57, 95% CI 1.12 to 2.20, p = 0.025) compared to the euthyroid group. Elevated levels of thyroid-stimulating hormone (TSH) were correlated with an increased risk of cardiovascular mortality (aHR: 1.03, 95% CI 1.01 to 1.05, p = 0.007) and hospitalizations (aHR: 1.06, 95% CI 1.01 to 1.12, p = 0.03). Conversely, lower levels of triiodothyronine (T3) were associated with higher risks of all-cause mortality (aHR: 0.51, 95% CI 0.31 to 0.82, p = 0.006) and cardiovascular mortality (aHR: 0.42, 95% CI 0.23 to 0.77, p = 0.005). Among patients with AF, hypothyroidism was associated with increased hospitalizations. Furthermore, elevated TSH levels and decreased T3 levels were linked to higher cardiovascular and all-cause mortality risks, respectively.

The prognostic impact of right ventricular-pulmonary arterial coupling in heart failure: a systematic review and meta-analysis.

The echocardiographic tricuspid annular plane systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio is a non-invasive surrogate of right ventricular-pulmonary arterial (RV-PA) coupling which corresponds well with the respective invasively derived index. Recently, a wealth of observational data has arisen, outlining its prognostic value in heart failure (HF) patients. To systematically appraise and quantitatively synthesize the evidence of the prognostic value of TAPSE/PASP ratio in left-sided HF regardless of etiology or left ventricular ejection fraction. A systematic literature review was conducted in electronic databases to identify studies reporting the association of TAPSE/PASP ratio with outcomes in patients with HF and, when appropriate, a random-effects meta-analysis was conducted to quantify the unadjusted and adjusted hazard ratios [(a)HRs] for all-cause death and the composite outcome of all-cause death or HF hospitalization. Eighteen studies were deemed eligible encompassing 8,699 HF patients. The applied cut-off value for RV-PA uncoupling varied substantially from 0.27 to 0.58 mm/mmHg, and in most studies values lower than the applied cutoff conveyed dismal prognosis. Eleven studies reported appropriate data for meta-analysis. TAPSE/PASP reduction by 1 mm/mmHg was independently associated with all-cause death (pooled aHR=1.32 [1.06-1.65]; p=0.01; I2=56%) and the composite outcome (pooled aHR=3.48 [1.67-7.25]; p<0.001; I2=0%). When a TAPSE/PASP cutoff value of 0.36 mm/mmHg was applied it yielded independent association with all-cause death (pooled aHR=2.84 [2.22-3.64]; p<0.001; I2=82%). RV-PA coupling assessed by echocardiographic TAPSE/PASP ratio appears to be an independent outcome predictor for HF patients.

P-wave Indices as Predictors of Atrial Fibrillation: The Lion from a Claw.

The P wave, representing the electrical fingerprint of atrial depolarization, contains information regarding spatial and temporal aspects of atrial electrical-and potentially structural-properties. However, technical and biological reasons, including-but not limited to-the low amplitude of the P wave and large interindividual variations in normal or pathologic atrial electrical activity, make gathering and utilizing this information for clinical purposes a rather cumbersome task. However, even crude ECG descriptors, such as P-wave dispersion, have been shown to be of predictive value for assessing the probability that a patient already has or will shortly present with AF. More sophisticated methods of analyzing the ECG signal, on a single- or multi- beat basis, along with novel approaches to data handling, namely machine learning, seem to be leading up to more accurate and robust ways to obtain clinically useful information from the humble P wave.

Diagnostic Puzzles and Cause-Targeted Treatment Strategies in Myocardial Infarction with Non-Obstructive Coronary Arteries: An Updated Review.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a distinct subtype of myocardial infarction (MI), occurring in about 8-10% of spontaneous MI cases referred for coronary angiography. Unlike MI with obstructive coronary artery disease, MINOCA's pathogenesis is more intricate and heterogeneous, involving mechanisms such as coronary thromboembolism, coronary vasospasm, microvascular dysfunction, dissection, or plaque rupture. Diagnosing MINOCA presents challenges and includes invasive and non-invasive strategies aiming to differentiate it from alternative diagnoses and confirm the criteria of elevated cardiac biomarkers, non-obstructive coronary arteries, and the absence of alternate explanations for the acute presentation. Tailored management strategies for MINOCA hinge on identifying the underlying cause of the infarction, necessitating systematic diagnostic approaches. Furthermore, determining the optimal post-MINOCA medication regimen remains uncertain. This review aims to comprehensively address the current state of knowledge, encompassing diagnostic and therapeutic approaches, in the context of MINOCA while also highlighting the evolving landscape and future directions for advancing our understanding and management of this intricate myocardial infarction subtype.

Prognostic Implications of Clinical, Laboratory and Echocardiographic Biomarkers in Patients with Acute Myocardial Infarction-Rationale and Design of the ''CLEAR-AMI Study''.

BACKGROUND: Acute myocardial infarction (AMI) remains a major cause of death worldwide. Survivors of AMI are particularly at high risk for additional cardiovascular events. Consequently, a comprehensive approach to secondary prevention is necessary to mitigate the occurrence of downstream complications. This may be achieved through a multiparametric tailored risk stratification by incorporating clinical, laboratory and echocardiographic parameters. METHODS: The ''CLEAR-AMI Study'' (ClinicalTrials.gov Identifier: NCT05791916) is a non-interventional, prospective study including consecutive patients with AMI without a known history of coronary artery disease. All patients satisfying these inclusion criteria are enrolled in the present study. The rationale of this study is to refine risk stratification by using clinical, laboratory and novel echocardiographic biomarkers. All the patients undergo a comprehensive transthoracic echocardiographic assessment, including strain and myocardial work analysis of the left and right heart chambers, within 48 h of admission after coronary angiography. Their laboratory profile focusing on systemic inflammation is captured during the first 24 h upon admission, and their demographic characteristics, past medical history, and therapeutic management are recorded. The angioplasty details are documented, the non-culprit coronary lesions are archived, and the SYNTAX score is employed to evaluate the complexity of coronary artery disease. A 24-month follow-up period will be recorded for all patients recruited. CONCLUSION: The ''CLEAR-AMI" study is an ongoing prospective registry endeavoring to refine risk assessment in patients with AMI without a known history of coronary artery disease, by incorporating echocardiographic parameters, biochemical indices, and clinical and coronary characteristics in the acute phase of AMI.

Concomitant Coronary Artery Disease in Identical Twins: Case Report and Systematic Literature Review.

Coronary artery disease (CAD) is multifactorial and strongly affected by genetic, epigenetic and environmental factors. Several studies have reported development of concomitant CAD in identical twins. We report a case in which a pair of Caucasian male monozygotic twins presented almost concomitantly with acute coronary syndrome (ACS) and had concordant coronary anatomy and identical site of occlusion. We performed a systematic literature review of PubMed, Web Of Science and Scopus databases from inception until 28 February 2023 of case reports/case series reporting the concomitant development of CAD in monozygotic twins. We found 25 eligible case reports with a total of 31 monozygotic twin pairs (including the case from our center) suffering from CAD and presenting (most of them simultaneously) with ACS (mean age of presentation: 45 ± 12 years, males: 81%). Coronary angiograms demonstrated lesion and anatomy concordance in 77% and 79% of the twin pairs, respectively. Screening for disease-related genetic mutations was performed in six twin pairs leading to the identification of five CAD-related genetic polymorphisms. This is the first systematic literature review of studies reporting identical twin pairs suffering from CAD. In summary, there is high concordance of coronary anatomy and clinical presentation between monozygotic twins. Future monozygotic twin studies-unbiased by age effects-can provide insights into CAD heritability being able to disentangle the traditional dyad of genetic and environmental factors and investigate the within-pair epigenetic drift.

Unmet Needs in the Assessment of Right Ventricular Function for Severe Tricuspid Regurgitation.

Tricuspid regurgitation (TR) is a highly prevalent valvular heart disease that has been long overlooked, but lately its independent association with adverse cardiovascular outcomes was recognized. The time point to intervene and repair the tricuspid valve is defined by the right ventricular (RV) dilation and dysfunction that comes up at a later stage. While guidelines favor tricuspid valve repair before severe RV dysfunction ensues, the definition of RV dysfunction in a universal manner remains vague. As a result, the candidates for transcatheter or surgical TR procedures are often referred late, when advanced RV dysfunction is established, and any derived procedural survival benefit is attenuated. Thus, it is of paramount importance to establish a universal means of RV function assessment in patients with TR. Conventional echocardiographic indices of RV function routinely applied have fundamental flaws that limit the precise characterization of RV performance. More recently, novel echocardiographic indices such as strain via speckle-tracking have emerged, demonstrating promising results in the identification of early RV damage. Additionally, evidence of the role of alternative imaging modalities such as cardiac computed tomography and cardiac magnetic resonance, for RV functional assessment in TR, has recently arisen. This review provides a systematic appraisal of traditional and novel multimodality indices of RV function in severe TR and aims to refine RV function assessment, designate future directions, and ultimately, to improve the outcome of patients suffering from severe TR.

Association of Length of Stay With the Clinical Trajectory of Hospitalized Patients With Atrial Fibrillation: Staying Less Is More?

Data predicting the length of stay (LOS) in patients with concurrent atrial fibrillation (AF) are scarce. This study aimed to investigate the potential predictors for prolonged LOS and its prognostic value. In this observational post hoc analysis of the MISOAC-AF (Motivational Interviewing to Support Oral AntiCoagulation adherence in patients with non-valvular Atrial Fibrillation) randomized trial logistic regression analyses were conducted to identify the parameters associated with prolonged LOS (defined as >7 days according to diagnostic accuracy analyses). Kaplan-Meier and Cox regression analyses were performed to generate survival curves and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the primary end point of all-cause mortality and for the secondary end points during a median 3.7-year follow-up. Of the 1,057 patients studied, 462 (43.7%) were hospitalized for ≥7 days. Heart failure with reduced ejection fracture (aHR 1.75, 95% CI 1.17 to 2.63), permanent AF (aHR 1.72, 95% CI 1.29 to 2.31), history of coronary artery disease (aHR 2.32, 95% CI 1.59 to 3.39), and advanced or end-stage chronic kidney disease (aHR 1.54, 95% CI 1.15 to 2.06) were independently associated with prolonged hospitalization. Prolonged LOS was independently linked with increased all-cause mortality rates (aHR 1.68, 95% CI 1.25 to 2.26), cardiovascular mortality (aHR 1.92, 95% CI 1.36 to 2.72), major bleeding (aHR 3.07, 95% CI 1.07 to 8.78), and the composite outcome of cardiovascular death or rehospitalization (aHR 1.31, 95% CI 1.04 to 1.66). Each extra day of LOS was an independent predictor of all-cause mortality (aHR 1.03, 95% CI 1.02 to 1.04). Hospitalized patients with concurrent AF carry a substantial morbidity burden being prone to extended LOS. A jointed approach seems reasonable to reduce the LOS in patients with AF.

Right Ventricular Global Longitudinal Strain and Short-Term Prognosis in Patients With First Acute Myocardial Infarction.

Right ventricular (RV) dysfunction after acute myocardial infarction (AMI) is a recognized predictor of dismal prognosis. However, the most reliable RV index to predict mortality early after revascularization remains undetermined. This study aimed to explore the ability of RV global longitudinal strain (GLS) to predict inhospital mortality in patients with first AMI. All consecutive patients with first AMI were prospectively enrolled from March 2022 until February 2023. An echocardiogram was performed 24 hours after successful revascularization and RV GLS alongside conventional echocardiographic indexes were measured. Inhospital mortality was recorded. A total of 300 patients (age 61.2 ± 11.8 years, 74% male) were included in the study. RV GLS was the only RV performance index that differed significantly between anterior and inferior ST-segment-elevation patients with AMI (14.5 ± 5.2% vs 17.4 ± 5.1% respectively, p <0.001). After revascularization, 23 patients (7.7%) died in hospital. The model of Global Registry of Acute Coronary Event risk score and left ventricular ejection fraction, built for predicting inhospital mortality, significantly improved its prognostic performance only by the addition of RV GLS (chi-square value increase by 7.485, p = 0.006) compared with the other RV function indexes. RV GLS was independently associated with inhospital mortality (odds ratio 0.83, 95% confidence interval 0.71 to 0.97, p = 0.017) after adjustment for Global Registry of Acute Coronary Event risk score and left ventricular ejection fraction. Echocardiographic RV GLS measured 24 hours after revascularization in patients with first AMI outperformed conventional RV function indexes in predicting inhospital mortality.

Risk of arterial thromboembolism, bleeding and mortality in atrial fibrillation patients with comorbid cancer: A systematic review and meta-analysis.

AIMS: Atrial fibrillation (AF) and cancer often co-exist. Each has been associated with an increased risk of morbidity and mortality. The aim of this meta-analysis was to synthesize available data regarding the incidence of arterial thromboembolism (TE), bleeding, and all-cause mortality in patients with AF with or without cancer. METHODS: Literature search was conducted in PubMed, Ovid MEDLINE, WebOfScience, Scopus, CENTRAL, OpenGrey, and EThOS databases to identify studies that included patients with AF and accounted for cancer status with the incidence of TE (ischemic stroke, transient ischemic attack, or arterial thrombosis), major or clinically relevant non-major bleeding, and all-cause mortality. A random-effects meta-analysis was used. RESULTS: Overall, 17 studies were included (3,149,547 patients). The risk of TE was similar in patients with AF with comorbid cancer compared with that in AF alone (pooled odds ratio [pOR] 0.97, 95% Confidence Interval [CI] 0.85-1.11, I2 = 87%). Major or clinically relevant non-major bleeding (pOR 1.65, 95% CI 1.35-2.02, I2 = 98%) and all-cause death (pOR 2.17, 95% CI 1.83-2.56, I2 = 98%) were significantly higher in patients with AF with cancer than in patients with AF only. The history of TE and hypertension and mean age were significant moderators of TE risk. CONCLUSION: In patients with AF, the presence of cancer is associated with a similar risk of TE as well as an increased risk of bleeding and all-cause death compared with the absence of cancer.

The prognostic value of right ventricular longitudinal strain in heart failure: a systematic review and meta-analysis.

BACKGROUND: Right ventricular (RV) dysfunction is a well-recognized adverse prognostic feature in patients with heart failure (HF). Recently, many single-center studies have demonstrated that RV longitudinal strain assessed using speckle tracking echocardiography might be a powerful prognosticator in HF. OBJECTIVES: To systematically appraise and quantitatively synthesize the evidence of the prognostic value of echocardiographic RV longitudinal strain, across the entire spectrum of left ventricular ejection function (LVEF) in HF. METHODS: A systematic literature review was conducted in electronic databases to identify every study reporting the predictive role of RV global longitudinal strain (RV GLS) and RV free wall longitudinal strain (RV FWLS) in HF subjects. A random-effects meta-analysis was conducted to quantify the adjusted and unadjusted hazard ratios [(a)HRs] for all-cause-mortality and for the composite outcome of all-cause mortality or HF-related hospitalization for both indices. RESULTS: Twenty-four studies were deemed eligible and 15 of these provided appropriate quantitative data for the meta-analysis, encompassing 8,738 patients. Each 1% worsening in RV GLS and RV FWLS was independently associated with increased risk of all-cause mortality (pooled aHR = 1.08 [1.03-1.13]; p < 0.01; I2 = 76% and 1.05 [1.05-1.06]; p < 0.01; I2 = 0%, respectively) and the composite outcome (pooled aHR = 1.10 [1.06-1.15]; p < 0.01; I2 = 0% and 1.06 [1.02-1.10]; p < 0.01; I2 = 69%, respectively) for patients with HF. The subgroup analysis of HF patients with LVEF < 45% yielded similar results, with worsening in RV GLS and RV FWLS retaining strong association with the two outcomes. CONCLUSION: Echocardiographic RV GLS and RV FWLS appear to have powerful prognostic value across the range of HF.

Changes in CHA2DS2-VASc score and risk of ischemic stroke among patients with atrial fibrillation.

AIMS: The CHA2DS2-VASc score is fundamental to stroke risk assessment in atrial fibrillation. However, stroke-related risk factors can be modified later in life. This study aimed to assess the association of changes in CHA2DS2-VASc score over time (Delta CHA2DS2-VASc score) with the risk of ischemic stroke. MATERIALS AND METHODS: This is an observational analysis of 1127 atrial fibrillation patients previously enrolled in the MISOAC-AF trial. After a median 2.6-year follow-up period, baseline and follow-up CHA2DS2-VASc scores were used to extract the Delta CHA2DS2-VASc score. The stroke predicting accuracies of the baseline, follow-up, and Delta CHA2DS2-VASc scores were assessed through regression analyses. RESULTS: The mean baseline, follow-up, and Delta CHA2DS2-VASc scores were 4.2, 4.8, and 0.6 respectively. Ischemic stroke occurred in 54 (4.4%) patients, of which 83.3% had a Delta CHA2DS2-VASc score ≥1, contrary to 40.1% of the stroke-free group. The stroke risk per 1-point increase of the CHA2DS2-VASc score was not significantly associated with the baseline score (aHR=1.14; 95%CI: 0.93-1.41; p=0.201), whereas a significant association was observed with the follow-up (aHR=2.58; 95% CI: 2.07-3.21; p<0.001) and Delta (aHR=4.56; 95%CI: 3.50-5.94; p<0.001) scores. C-index assessment indicated that follow-up and Delta CHA2DS2-VASc scores were more potent predictors of ischemic stroke compared to baseline. CONCLUSION: In atrial fibrillation patients, changes in CHA2DS2-VASc score over time were associated with the incidence of stroke. The improved predictability of follow-up and Delta CHA2DS2-VASc scores indicates that stroke risk is not a static parameter. TRIAL REGISTRATION: This is an observational, post-hoc analysis of the MISOAC-AF randomized controlled trial, registered on ClinicalTrials.gov (identifier: NCT02941978; registered: October 21, 2016).