The impact of anticoagulation therapy on kidney function in patients with atrial fibrillation and chronic kidney disease.

INTRODUCTION: Atrial fibrillation (AF) and chronic kidney disease (CKD) are closely related. These diseases share common risk factors and are associated with increased risk of thromboembolic events. Choosing the appropriate oral anticoagulant therapy (OAC) in patients with AF and CKD is challenging. Deterioration of renal function is common in patients with AF treated with OACs, although not all OACs affect the kidneys equally. AREAS COVERED: In this review, we aim to summarize the current knowledge of the prevention of thromboembolic events in patients with AF and CKD, focusing on the impact of specific OAC agents on renal function. EXPERT OPINION: Consideration of OAC use is mandatory in patients with AF and CKD who are at increased risk of stroke or systemic embolism. Available evidence suggests that the use of non-vitamin K antagonist oral anticoagulants (NOACs) is associated with slower deterioration of renal function in comparison to Vitamin K antagonists (VKAs). Hence, a NOAC should be used in preference to VKAs in all NOAC-eligible patients with AF and CKD. Regarding patients with end-stage renal dysfunction and those on dialysis or renal replacement therapy, the use of NOAC should be considered in line with locally relevant formal recommendations.

Long-Term Renal Function after Catheter Ablation of Atrial Fibrillation.

Background: Atrial fibrillation (AF) is associated with the development and progression of chronic kidney disease (CKD). This study evaluated the impact of long-term rhythm outcome after catheter ablation (CA) of AF on renal function. Methods and results: The study group included 169 consecutive patients (the mean age was 59.6 ± 10.1 years, 61.5% were males) who underwent their first CA of AF. Renal function was assessed by eGFR (using the CKD-EPI and MDRD formulas), and by creatinine clearance (using the Cockcroft-Gault formula) in each patient before and 5 years after index CA procedure. During the 5-year follow-up after CA, the late recurrence of atrial arrhythmia (LRAA) was documented in 62 patients (36.7%). The mean eGFR, regardless of which formula was used, significantly decreased at 5 years following CA in patients with LRAA (all p < 0.05). In the arrhythmia-free patients, the mean eGFR at 5 years post-CA remained stable (for the CKD-EPI formula: 78.7 ± 17.3 vs. 79.4 ± 17.4, p = 0.555) or even significantly improved (for the MDRD formula: 74.1 ± 17.0 vs. 77.4 ± 19.6, p = 0.029) compared with the baseline. In the multivariable analysis, the independent risk factors for rapid CKD progression (decline in eGFR > 5 mL/min/1.73 m2 per year) were the post-ablation LRAA occurrence (hazard ratio 3.36 [95% CI: 1.25-9.06], p = 0.016), female sex (3.05 [1.13-8.20], p = 0.027), vitamin K antagonists (3.32 [1.28-8.58], p = 0.013), or mineralocorticoid receptor antagonists' use (3.28 [1.13-9.54], p = 0.029) after CA. Conclusions: LRAA after CA is associated with a significant decrease in eGFR, and it is an independent risk factor for rapid CKD progression. Conversely, eGFR in arrhythmia-free patients after CA remained stable or even improved significantly.

Sex-related differences in self-reported treatment burden in patients with atrial fibrillation.

Background: Treatment burden (TB) is defined as the patient's workload of healthcare and its impact on patient functioning and wellbeing. High TB can lead to non-adherence, a higher risk of adverse outcomes and lower quality of life (QoL). We have previously reported a higher TB in patients with atrial fibrillation (AF) vs. those with other chronic conditions. In this analysis, we explored sex-related differences in self-reported TB in AF patients. Materials and methods: A single-center, prospective study included consecutive patients with AF under drug treatment for at least 6 months before enrollment from April to June 2019. Patients were asked to voluntarily and anonymously answer the Treatment Burden Questionnaire (TBQ). All patients signed the written consent for participation. Results: Of 331 patients (mean age 65.4 ± 10.3 years, mean total AF history 6.41 ± 6.62 years), 127 (38.4%) were females. The mean TB was significantly higher in females compared to males (53.7 vs. 42.6 out of 170 points, p < 0.001), and females more frequently reported TB ≥ 59 points than males (37.8% vs. 20.6%, p = 0.001). In females, on multivariable analysis of the highest TB quartile (TB ≥ 59), non-vitamin K Antagonist Oral Anticoagulant (NOAC) use [Odds Ratio (OR) 0.319; 95% Confidence Interval (CI) 0.12-0.83, P = 0.019], while in males, catheter ablation and/or ECV of AF (OR 0.383; 95% CI 0.18-0.81, P = 0.012) were negatively associated with the highest TB quartile. Conclusion: Our study was the first to explore the sex-specific determinants of TB in AF patients. Females had significantly higher TB compared with males. Approximately 2 in 5 females and 1 in 5 males reported TB ≥ 59 points, previously shown to be an unacceptable burden of treatment for patients. Using a NOAC rather than vitamin K antagonist (VKA) in females and a rhythm control strategy in males could decrease TB to acceptable values.

Predictors of Adherence to Stroke Prevention in the BALKAN-AF Study: A Machine-Learning Approach.

Background Compared with usual care, guideline-adherent stroke prevention strategy, based on the ABC (Atrial fibrillation Better Care) pathway, is associated with better outcomes. Given that stroke prevention is central to atrial fibrillation (AF) management, improved efforts to determining predictors of adherence with 'A' (avoid stroke) component of the ABC pathway are needed. Purpose We tested the hypothesis that more sophisticated methodology using machine learning (ML) algorithms could do this. Methods In this post-hoc analysis of the BALKAN-AF dataset, ML algorithms and logistic regression were tested. The feature selection process identified a subset of variables that were most relevant for creating the model. Adherence with the 'A' criterion of the ABC pathway was defined as the use of oral anticoagulants (OAC) in patients with AF with a CHA 2 DS 2 -VASc score of 0 (male) or 1 (female). Results Among 2,712 enrolled patients, complete data on 'A'-adherent management were available in 2,671 individuals (mean age 66.0 ± 12.8; 44.5% female). Based on ML algorithms, independent predictors of 'A-criterion adherent management' were paroxysmal AF, center in capital city, and first-diagnosed AF. Hypertrophic cardiomyopathy, chronic kidney disease with chronic dialysis, and sleep apnea were independently associated with a lower likelihood of 'A'-criterion adherent management. ML evaluated predictors of adherence with the 'A' criterion of the ABC pathway derived an area under the receiver-operator curve of 0.710 (95%CI 0.67-0.75) for random forest with fine tuning. Conclusions Machine learning identified paroxysmal AF, treatment center in the capital city, and first-diagnosed AF as predictors of adherence to the A pathway; and hypertrophic cardiomyopathy, chronic kidney disease with chronic dialysis, and sleep apnea as predictors of non adherence.

Adherence to the 4S-AF Scheme in the Balkan region: Insights from the BALKAN-AF survey.

BACKGROUND: The 4S-AF scheme includes stroke risk, symptoms, severity of burden, and substrate severity domain. AIM: We aimed to assess the adherence to the 4S-AF scheme in patients classified according to stroke risk in post hoc analysis of the BALKAN-AF dataset. METHODS: A 14-week prospective enrolment of consecutive patients with electrocardiographically documented atrial fibrillation (AF) was performed in seven Balkan countries from 2014 to 2015. RESULTS: Low stroke risk (CHA2DS2-VASc score, 0 in males or 1 in females) was present in 162 (6.0%) patients. 2 099 (77.4%) patients had CHA2DS2-VASc score ≥3 in females or ≥2 in males (high stroke risk), and 613 (22.6%) had CHA2DS2-VASc score <3 in females or <2 in males. Seventy-five (46.3%) patients with low stroke risk and 1555 (74.1%) patients with high stroke risk were prescribed oral anticoagulants (OAC). Two thousand six hundred and seventy-seven (98.6%) had data on European Heart Rhythm Association (EHRA) class. Among 2099 patients with high stroke risk, 703 (33.4%) had EHRA class ≥3. Two hundred and seven (29.4%) patients with EHRA class ≥3 and high stroke risk were offered rhythm control; 620 (55.2%) of individuals with first-diagnosed or paroxysmal AF with high stroke risk were offered rhythm control. Two or more comorbidities occurred in 1927 (91.8%) patients with high stroke risk. CONCLUSIONS: OAC overuse was observed in patients with low stroke risk, whilst OAC underuse was evident in those with high risk of stroke. The percentage of highly symptomatic patients with high risk of stroke who were offered a rhythm control strategy was low.

Quality indicators in the management of atrial fibrillation: the BALKAN-AF survey.

BACKGROUND: The implementation of quality indicators in the atrial fibrillation (AF) care should be considered to improve quality of management and patient outcome. METHODS: In the post-hoc analysis of the BALKAN-AF dataset, we assessed concordance with quality indicators for AF management. Available domains for AF management [patient assessment (baseline), anticoagulation, rate control strategy, rhythm control strategy and risk factor management] were identified and assessed at baseline visit. RESULTS: Among 132 patients with a CHA2DS2-VASc score of 0 (men) or 1 (women), 75 (56.8%) were prescribed oral anticoagulation (OAC). Of 2539 patients with a CHA2DS2-VASc score ≥ 1 for men and ≥ 2 for women, 1890 (74.4%) were prescribed OAC. Among 1088 patients with permanent AF, 110 (10.1%) individuals were prescribed antiarrhythmic drugs (AADs). Of 1616 patients with structural heart disease, 37 (2.2%) were prescribed class IC AADs. Of 1624 patients with paroxysmal or persistent AF, 59 (3.6%) were offered catheter ablation. Among 2712 AF patients, 2121 (78.2%) had hypertension, 671 (24.7%) were obese, 53 (2.0%) had obstructive sleep apnoea, 110 (4.0%) had alcohol abuse and 340 (12.5%) were smokers. CONCLUSIONS: In the BALKAN-AF cohort, the use of OAC for stroke prevention was poorly associated with patients stroke risk. The use of AADs in patients with permanent AF was low. The prescription of class IC AADs to patients with structural heart disease was infrequent. A large proportion of AF patients had their modifiable risk factors identified.

Symptom management strategies: Rhythm vs rate control in patients with atrial fibrillation in the Balkan region: Data from the BALKAN-AF survey.

BACKGROUND: Symptom-focused management is one of the cornerstones of optimal atrial fibrillation (AF) therapy. OBJECTIVES: To evaluate the use of rhythm control and rate control strategy. Second, to identify predictors of the use of amiodarone in patients with rhythm control and of the use of rhythm control strategy in patients with paroxysmal AF in the Balkans. METHODS: Prospective enrolment of consecutive patients from seven Balkan countries to the BALKAN-AF survey was performed. RESULTS: Of 2712 enrolled patients, 2522 (93.0%) with complete data were included: 1622 (64.3%) patients were assigned to rate control strategy and 900 (35.7%) to rhythm control. Patients with rhythm control were younger, more often hospitalised for AF and with less comorbidities (all P < .05) than those with rate control. Symptom score [European Heart Rhythm Association (EHRA)] was not an independent predictor of a rhythm control strategy [odds ratio (OR) 0.99, 95% confidence interval (CI) 0.90-1.10, P = .945]. The most commonly chosen antiarrhythmic agents were amiodarone (49.7%), followed by propafenone (24.3%). CONCLUSION: More than one-third of patients in the BALKAN-AF survey received a rhythm control strategy, and these patients tended to be younger with less comorbidities than those managed with rate control. EHRA symptom score is not significantly associated with rhythm control strategy. The most commonly used antiarrhythmic agents were amiodarone, followed by propafenone.

Self-reported treatment burden in patients with atrial fibrillation: quantification, major determinants, and implications for integrated holistic management of the arrhythmia.

AIMS: Treatment burden (TB) refers to self-perceived cumulative work patients do to manage their health. Using validated tools, TB has been documented in several chronic conditions, but not atrial fibrillation (AF). We measured TB and analysed its determinants and impact on quality of life (QoL) in an AF cohort. METHODS AND RESULTS: A single-centre study prospectively included consecutive adult AF patients and non-AF controls managed from 1 April to 21 June 2019, who voluntarily and anonymously answered the TB questionnaire (TBQ) and 5-item EQ-5D QoL questionnaire; TB was calculated as a sum of TBQ points (maximum 170) and expressed as proportion of the maximum value. Of 514 participants, 331 (64.4%) had AF. The mean self-reported TB was 27.6% among AF patients and 24.3% among controls, P = 0.011. The mean TB was significantly higher in patients taking vitamin K antagonists (VKAs) vs. those taking non-VKA antagonist oral anticoagulants (NOAC; 29.5% vs. 24.7%, P = 0.006). The highest item-specific TB was reported for healthcare system organization-related items (e.g. visit appointment), diet, and physical activity modifications. On multivariable analyses, female sex, younger age, and permanent AF were associated with a higher TB, whereas NOACs and electrical AF cardioversion exhibited an inverse association; TB was an independent predictor of decreased QoL (all P < 0.05). CONCLUSION: Our study provided clinically relevant insights into self-perceived TB among AF patients. Approximately one in four patients with AF have a high TB. Specific AF treatments and optimization of healthcare system-required patient activities may reduce the self-perceived TB in AF patients.

Antithrombotic therapy in patients with atrial fibrillation and acute coronary syndrome and / or undergoing percutaneous coronary intervention.

The use of triple antithrombotic therapy (TAT) consisting of an oral anticoagulant (OAC), aspirin, and a P2Y12 inhibitor in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) and / or undergoing percutaneous coronary intervention (PCI) is associated with a high risk of bleeding. Recently, several randomized clinical trials tested the hypothesis as to whether dual antithrombotic therapy (DAT) regimens (consisting of an OAC and a single antiplatelet drug) may be safer in terms of bleeding events as compared with TAT. They also investigated the role of non-vitamin K antagonist oral anticoagulants (NOACs) as a part of DAT and TAT. The purpose of this review is to provide an overview of available evidence regarding the safety and efficacy of DAT compared with TAT regimens, international guidelines recommendations, knowledge gaps, and unmet needs in the management of patients with AF and ACS and / or undergoing PCI.

Risk factor modification for the primary and secondary prevention of atrial fibrillation. Part 1.

Modifiable risk factors, such as cardiometabolic and lifestyle risk factors, considerably contribute to (bi)atrial remodeling, finally resulting in clinical occurrence of atrial fibrillation (AF). Early identification and prompt intervention on these risk factors may delay further progression of atrial arrhythmia substrate and prevent the occurrence of new­onset AF. Moreover, in patients with previous history of recurrent AF, aggressive risk factor management may improve efficacy of other rhythm control strategies, including antiarrhythmic drugs and catheter ablation in sinus rhythm maintenance. Finally, modification of risk factors improves overall health and reduces cardiovascular mortality and morbidity. The first part of this review evaluates the association between AF and the following risk factors: hypertension, diabetes mellitus, physical activity, and cigarette smoking. We systematically discuss the impact of risk factor modification on primary and secondary prevention of AF.

Risk factor modification for the primary and secondary prevention of atrial fibrillation. Part 2.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased risk of death, stroke, and heart failure. Prevalence and incidence of AF are rising due to better overall medical treatment, longer survival, and increasing incidence of cardiometabolic and lifestyle risk factors. Treatment of AF and AF­related complications significantly increases healthcare costs. In addition, the use of conventional rhythm control strategies (including, antiarrhythmic drugs and catheter ablation) is associated with limited efficacy for sinus rhythm maintenance and serious adverse effects. Aggressive cardiometabolic risk factor management may prevent incident as well as recurrent AF, improve overall health, and reduce mortality. Therefore, modifiable risk factor management became one of the 3 treatment pillars in AF management along with anticoagulation as well as conventional rate and rhythm control strategies. The second part of this review systematically discusses the association between AF and potentially modifiable risk factors for AF, such as obesity, obstructive sleep apnea, alcohol consumption, and dyslipidemia. We also provide practical guidelines for the risk factor management with respect to primary and secondary prevention of AF.

External Validation of the Simple NULL-PLEASE Clinical Score in Predicting Outcome of Out-of-Hospital Cardiac Arrest.

BACKGROUND: Rapid clinical decision-making on further management of patients with out-of-hospital cardiac arrest may be challenging. Recently, a "futility" score (NULL-PLEASE) incorporating multiple adverse resuscitation features (Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood PH <7.2, Lactate >7.0 mmol/L, End-stage chronic kidney disease on dialysis, Age ≥85 years, Still resuscitation, and Extracardiac cause) has been proposed to help identify patients with out-of-hospital cardiac arrest unlikely to survive; however, external independent score validation is lacking. METHODS: We retrospectively validated the NULL-PLEASE predictive ability for early in-hospital outcome of out-of-hospital cardiac arrest in a single-center cohort of 547 consecutive patients with out-of-hospital cardiac arrest who were admitted from April 2013 to October 2016 (mean age, 66.3 ± 13.2 years); 227 patients (41.5%) died. Because pH and lactate were inconsistently measured, a modified NULL-PLEASE score excluding both variables was calculated as the principal analysis. A sensitivity analysis included the subgroup with pH data available (n = 177). RESULTS: Long low-flow period and age ≥85 years were independently associated with fatal outcome (both P < .001). Patients with a modified NULL-PLEASE score of ≥5 had a 3.3-fold greater risk of fatal outcome compared with a score of 0 to 4 (odds ratio, 3.34; 95% confidence interval [CI], 2.29-4.89; P < .001); 77% of nonsurvivors had a score ≥5; NULL-PLEASE showed a modest predictive ability for fatal outcome (c-statistic 0.658; 95% CI, 0.613-0.704; P < .001). Sensitivity analysis yielded similar results, with 88% of nonsurvivors having a score ≥5. CONCLUSIONS: The NULL-PLEASE score was predictive for early in-hospital outcome of out-of-hospital cardiac arrest, with a 3.3-fold greater odds for fatal outcome at the score values of ≥5.