Long-term hyperuricemia impact on atrial fibrillation outcomes.

BACKGROUND: No studies have been conducted to analyze the impact of serum uric acid (UA) levels on the outcome of atrial fibrillation (AF) patients. We aimed to evaluate the effect of hyperuricemia (HU) on the prognosis of AF. METHODS AND RESULTS: Consecutive patients who consulted our emergency room for an episode of AF, already known or newly diagnosed, between January 1, 2010, and December 31, 2015 (n=2017) were enrolled. After applying exclusion criteria, 1772 patients were included. Serum UA levels in the 6 months before or after the date of the episode were recorded and classified into quartiles: Q1 (n=443) serum UA levels <4.6 mg/dL; Q2 (n=430) 4.6-5.6 mg/dL; Q3 (n=435) 5.7-6.9 mg/dL; and Q4 (n=464) ≥7 mg/dL. Two groups were differentiated: patients without HU (Q1-Q3) and those with HU (Q4). The mean follow-up was 3.7 ± 1.4 years. The primary endpoint was all-cause mortality during follow-up. Mortality during follow-up in the bivariate analysis was higher (p < 0.001) in patients with HU (52.1 %) compared to those without it (35.3 %), confirming multivariate Cox analysis of HU as an independent risk factor for death [hazard ratio 1.89 (1.59-2.25)]. Kaplan-Meier survival analysis showed a shorter survival time in patients with HU (log-rank test, p<0.001). Cox analysis confirmed significant differences in the risk of heart failure (30 % vs. 22 %) in patients with HU. CONCLUSIONS: HU is independently associated with an increased risk for all-cause mortality and hospitalization for heart failure in patients with AF.

Use of a New Standardized Unfractionated Heparin Protocol for Left-Sided Ablation Procedures Improves Time in the Therapeutic ACT Range.

OBJECTIVES: This study evaluated whether a novel standardized heparin dosing protocol used during atrial fibrillation catheter ablation resulted in a higher percentage of therapeutic activated clotting time (ACT) values compared to historic nonstandardized procedures. DESIGN: A retrospective cohort study SETTING: This study was conducted at Ochsner Medical Center, the largest tertiary-care teaching hospital in New Orleans, LA PARTICIPANTS: Patients undergoing catheter-based atrial fibrillation ablation INTERVENTIONS: The authors implemented a standardized heparin protocol, and enrolled 202 patients between November 2020 and March 2021. The historic controls consisted of 173 patients who underwent atrial fibrillation ablation between April 2020 and September 2020. Heparin administration in the control group was based on physician preference and was nonstandardized. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the percentage of intraprocedural ACTs in therapeutic range (≥300 to <450 s). Secondary endpoints included first measured ACT at ≥300 s and percent of measured ACTs in the supratherapeutic range (>450 s). Comparisons were performed using chi-squared tests or Fisher exact tests. Patients in the intervention group had a higher mean percentage of ACTs in the therapeutic range compared to the control group (84.9% vs. 75.8%, p<0.001). More patients in the intervention group reached therapeutic ACT on the first measurement compared to the control group (70.3% vs. 31.2%, p<0.001). CONCLUSION: During catheter-based cardiac ablation procedures, a novel standardized unfractionated heparin dosing protocol resulted in a higher percentage of ACTs in the target range, and a higher proportion of initial ACTs in the therapeutic range compared with baseline nonstandardized heparin dosing.

Which should you choose for post operative atrial fibrillation, carvedilol or metoprolol? A systemic review and meta-analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common arrhythmic complication following cardiac surgery. Current guidelines suggest beta-blockers for the prevention of POAF. In comparing metoprolol succinate with carvedilol, the later has sparked interest in its usage as an important medication for POAF prevention. METHODS: We considered randomized controlled studies (RCTs) and retrospective studies that evaluated the efficacy of carvedilol versus metoprolol for the prevention of POAF. After literature search, data extraction, and quality evaluation, pooled data were analyzed using either the fixed-effect or random-effect model using Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The incidence of POAF was the primary endpoint, while mortality rate and bradycardia were secondary outcomes. RESULTS: In meta-analysis 5 RCTs and 2 retrospective studies with a total of 1000 patients were included. The overall effect did not favor the carvedilol over metoprolol groups in terms of mortality rate [risk ratio 0.45, 95 % CI (0.1-1.97), P=0.29] or incidence of bradycardia [risk ratio 0.63, 95 % CI (0.32-1.23), P=0.17]. However, the incidence of POAF was lower in patients who received carvedilol compared to metoprolol [risk ratio 0.54, 95 % CI (0.42-0.71), P < 0.00001]. CONCLUSION: In patients undergoing cardiac surgery, carvedilol may minimize the occurrence of POAF more effectively than metoprolol. To definitively establish the efficacy of carvedilol compared to metoprolol and other beta-blockers in the prevention of POAF, a large-scale, well-designed randomized controlled trials are required.

Gender-Based Clinical, Therapeutic Strategies and Prognosis Differences in Atrial Fibrillation.

BACKGROUND: There are limited data on gender-based differences in atrial fibrillation (AF) treatment and prognosis. We aimed to examine gender-related differences in medical attention in an emergency department (ED) and follow-up (FU) among patients diagnosed with an AF episode and to determine whether there are gender-related differences in clinical characteristics, therapeutic strategies, and long-term adverse events in this population. METHODS: We performed a retrospective observational study of patients who presented to a tertiary hospital ER for AF from 2010 to 2015, with a minimum FU of one year. Data on medical attention received, mortality, and other adverse outcomes were collected and analyzed. RESULTS: Among the 2013 patients selected, 1232 (60%) were female. Women were less likely than men to be evaluated by a cardiologist during the ED visit (11.5% vs. 16.6%, p = 0.001) and were less likely to be admitted (5.9% vs. 9.5%, p < 0.05). Electrical cardioversion was performed more frequently in men, both during the first episode (3.4% vs. 1.2%, p = 0.001) and during FU (15.9% vs. 10.6%, p < 0.001), despite a lower AF recurrence rate in women (9.9% vs. 18.1%). During FU, women had more hospitalizations for heart failure (26.2% vs. 16.1%, p < 0.001). CONCLUSIONS: In patients with AF, although there were no gender differences in mortality, there were significant differences in clinical outcomes, medical attention received, and therapeutic strategies. Women underwent fewer attempts at cardioversion, had a lower probability of being evaluated by cardiologists, and showed a higher probability of hospitalization for heart failure. Being alert to these inequities should facilitate the adoption of measures to correct them.

Assessment of resting myocardial blood flow in regions of known transmural scar to confirm accuracy and precision of 3D cardiac positron emission tomography.

BACKGROUND: Composite invasive and non-invasive data consistently demonstrate that resting myocardial blood flow (rMBF) in regions of known transmural myocardial scar (TMS) converge on a value of ~ 0.30 mL/min/g or lower. This value has been confirmed using the 3 most common myocardial perfusion agents (13N, 15O-H2O and 82Rb) incorporating various kinetic models on older 2D positron emission tomography (PET) systems. Thus, rMBF in regions of TMS can serve as a reference "truth" to evaluate low-end accuracy of various PET systems and software packages (SWPs). Using 82Rb on a contemporary 3D-PET-CT system, we sought to determine whether currently available SWP can accurately and precisely measure rMBF in regions of known TMS. RESULTS: Median rMBF (in mL/min/g) and COV in regions of TMS were 0.71 [IQR 0.52-1.02] and 0.16 with 4DM; 0.41 [0.34-0.54] and 0.10 with 4DM-FVD; 0.66 [0.51-0.85] and 0.11 with Cedars; 0.51 [0.43-0.61] and 0.08 with Emory-Votaw; 0.37 [0.30-0.42], 0.07 with Emory-Ottawa, and 0.26 [0.23-0.32], COV 0.07 with HeartSee. CONCLUSIONS: SWPs varied widely in low end accuracy based on measurement of rMBF in regions of known TMS. 3D PET using 82Rb and HeartSee software accurately (0.26 mL/min/g, consistent with established values) and precisely (COV = 0.07) quantified rMBF in regions of TMS. The Emory-Ottawa software yielded the next-best accuracy (0.37 mL/min/g), though rMBF was higher than established gold-standard values in ~ 5% of the resting scans. 4DM, 4DM-FDV, Cedars and Emory-Votaw SWP consistently resulted values higher than the established gold standard (0.71, 0.41, 0.66, 0.51 mL/min/g, respectively), with higher interscan variability (0.16, 0.11, 0.11, and 0.09, respectively). TRIAL REGISTRATION: clinicaltrial.gov, NCT05286593, Registered December 28, 2021, https://clinicaltrials.gov/ct2/show/NCT05286593 .

Risk of ventricular arrhythmias following implantable cardioverter-defibrillator generator change in patients with recovered ejection fraction: Implications for shared decision-making.

INTRODUCTION: Guidelines indicate primary-prevention implantable cardioverter-defibrillators (ICDs) for most patients with left ventricular ejection fraction (LVEF) ≤ 35%. Some patients' LVEFs improve during the life of their first ICD. In patients with recovered LVEF who never received appropriate ICD therapy, the utility of generator replacement upon battery depletion remains unclear. Here, we evaluate ICD therapy based on LVEF at the time of generator change, to educate shared decision-making regarding whether to replace the depleted ICD. METHODS: We followed patients with a primary-prevention ICD who underwent generator change. Patients who received appropriate ICD therapy for ventricular tachycardia or ventricular fibrillation (VT/VF) before generator change were excluded. The primary endpoint was appropriate ICD therapy, adjusted for the competing risk of death. RESULTS: Among 951 generator changes, 423 met inclusion criteria. During 3.4 ± 2.2 years follow-up, 78 (18%) received appropriate therapy for VT/VF. Compared to patients with recovered LVEF > 35% (n = 161 [38%]), those with LVEF ≤ 35% (n = 262 [62%]) were more likely to require ICD therapy (p = .002; Fine-Gray adjusted 5-year event rates: 12.7% vs. 25.0%). Receiver operating characteristic analysis revealed the optimal LVEF cutoff for VT/VF prediction to be 45%, the use of which further improved risk stratification (p < .001), with Fine-Gray adjusted 5-year rates 6.2% versus 25.1%. CONCLUSION: Following ICD generator change, patients with primary-prevention ICDs and recovered LVEF have significantly lower risk of subsequent ventricular arrhythmias compared to those with persistent LVEF depression. Risk stratification at LVEF 45% offers significant additional negative predictive value over a 35% cutoff, without a significant loss in sensitivity. These data may be useful during shared decision-making at the time of ICD generator battery depletion.

Design and development of a digital shared decision-making tool for stroke prevention in atrial fibrillation.

Background: Shared decision-making (SDM) is an approach in which patients and clinicians act as partners in making medical decisions. Patients receive the information needed to decide and are encouraged to balance risks, benefits, and preferences. Informative materials are vital to SDM. Atrial fibrillation (AF) is the most common cardiac arrhythmia and responsible for 10% of ischemic strokes, however 1/3 of patients are not on appropriate anticoagulation. Decision sharing may facilitate treatment acceptance, improving outcomes. Aims: To develop a framework of the components needed to create novel SDM tools and to provide practical examples through a case-study of stroke prevention in AF. Methods: We analyze the design values of a web-based SDM tool created to better inform AF patients about anticoagulation. The tool was developed in partnership with patient advocates, multi-disciplinary investigators, and private design firms. It was refined through iterative, recursive testing in patients with AF. Its effectiveness is being evaluated in a multisite clinical trial led by Stanford University and sponsored by the American Heart Association. Findings: The main components considered when creating the Stanford AFib tool included: design and software; content identification; information delivery; inclusive communication, user engagement; patient feedback; clinician experience; and anticipation of implementation and dissemination. We also highlight the ethical principles underlying SDM; matters of diversity and inclusion, linguistic variety, accessibility, and health literacy. The Stanford AFib Guide patient tool is available at: https://afibguide.com and the clinician tool at https://afibguide.com/clinician. Conclusion: Attention to a range of vital development and design factors can facilitate tool adoption and information acquisition by diverse cultural, educational, and socioeconomic subpopulations. With thoughtful design, digital tools may decrease decision regret and improve treatment outcomes across many decision-making situations in healthcare.

Randomized Clinical Trial to Evaluate an Atrial Fibrillation Stroke Prevention Shared Decision-Making Pathway.

Background Oral anticoagulation reduces stroke and disability in atrial fibrillation (AF) but is underused. We evaluated the effects of a novel patient-clinician shared decision-making (SDM) tool in reducing oral anticoagulation patient's decisional conflict as compared with usual care. Methods and Results We designed and evaluated a new digital decision aid in a multicenter, randomized, comparative effectiveness trial, ENHANCE-AF (Engaging Patients to Help Achieve Increased Patient Choice and Engagement for AF Stroke Prevention). The digital AF shared decision-making toolkit was developed using patient-centered design with clear health communication principles (eg, meaningful images, limited text). Available in English and Spanish, the toolkit included the following: (1) a brief animated video; (2) interactive questions with answers; (3) a quiz to check on understanding; (4) a worksheet to be used by the patient during the encounter; and (5) an online guide for clinicians. The study population included English or Spanish speakers with nonvalvular AF and a CHA2DS2-VASc stroke score ≥1 for men or ≥2 for women. Participants were randomized in a 1:1 ratio to either usual care or the shared decision-making toolkit. The primary end point was the validated 16-item Decision Conflict Scale at 1 month. Secondary outcomes included Decision Conflict Scale at 6 months and the 10-item Decision Regret Scale at 1 and 6 months as well as a weighted average of Mann-Whitney U-statistics for both the Decision Conflict Scale and the Decision Regret Scale. A total of 1001 participants were enrolled and followed at 5 different sites in the United States between December 18, 2019, and August 17, 2022. The mean patient age was 69±10 years (40% women, 16.9% Black, 4.5% Hispanic, 3.6% Asian), and 50% of participants had CHA2DS2-VASc scores ≥3 (men) or ≥4 (women). The primary end point at 1 month showed a clinically meaningful reduction in decisional conflict: a 7-point difference in median scores between the 2 arms (16.4 versus 9.4; Mann-Whitney U-statistics=0.550; P=0.007). For the secondary end point of 1-month Decision Regret Scale, the difference in median scores between arms was 5 points in the direction of less decisional regret (P=0.078). The treatment effects lessened over time: at 6 months the difference in medians was 4.7 points for Decision Conflict Scale (P=0.060) and 0 points for Decision Regret Scale (P=0.35). Conclusions Implementation of a novel shared decision-making toolkit (afibguide.com; afibguide.com/clinician) achieved significantly lower decisional conflict compared with usual care in patients with AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096781.

Sacubitril/valsartan: An antiarrhythmic drug?

INTRODUCTION: Heart failure (HF) is a major cause of morbidity and mortality, with nearly half of all HF-related deaths resulting from sudden cardiac death (SCD), most often from an arrhythmic event. The pathophysiologic changes that occur in response to the hemodynamic stress of HF may lead to increased arrhythmogenesis. Theoretically, medications that block these arrhythmogenic substrates would decrease the risk of SCD. The combined angiotensin receptor and neprilysin inhibitor (ARNi; tradename Entresto) is the newest commercially available medication for the treatment of heart failure. METHODS AND RESULTS: We reviewed and synthesized the available literature regarding sacubitril/valsartan and its effects on cardiac rhythm. ARNi has been shown to decrease cardiovascular mortality and hospitalization in patients with HF with reduced ejection fraction (HFrEF). Emerging evidence suggests that ARNi also may play a role in reducing arrhythmogenesis and thereby SCD. CONCLUSION: This review summarizes the current data regarding this ARNi and its potential antiarrhythmic effects.

The complex interplay between diabetes mellitus and atrial fibrillation.

INTRODUCTION: A growing body of evidence suggests that diabetes mellitus (DM) is associated with an increased risk of new-onset atrial fibrillation (AF) and contributes to suboptimal arrhythmia control and poor prognosis in patients with AF. The high prevalence of AF among patients with DM is primarily attributed to common risk factors, shared pathophysiological mechanisms, and associated atrial remodeling and autonomic dysfunction. AREAS COVERED: This comprehensive review covers the current data on the role of DM in the development and prognosis of AF. In addition, we review the impact of anti-DM medications on AF prevention and the role of anticoagulation in patients with coexisting DM and AF. EXPERT OPINION: DM is independently associated with new-onset AF, and the coexistence of these two conditions contributes to poor outcomes, from reduced quality of life to increased risks of thromboembolic events, heart failure, and mortality. Despite this strong link, the current evidence is insufficient to recommend routine screening for AF in patients with DM. Although some observations exist on preventing AF with anti-DM medications, randomized controlled trials are warranted to explore the proposed benefits of novel anti-DM medicines in reducing the risk of incident AF.

The ENHANCE-AF clinical trial to evaluate an atrial fibrillation shared decision-making pathway: Rationale and study design.

INTRODUCTION: Shared decision making (SDM) may result in treatment plans that best reflect the goals and wishes of patients, increasing patient satisfaction with the decision-making process. There is a knowledge gap to support the use of decision aids in SDM for anticoagulation therapy in patients with atrial fibrillation (AF). We describe the development and testing of a new decision aid, including a multicenter, randomized, controlled, 2-arm, open-label ENHANCE-AF clinical trial (Engaging Patients to Help Achieve Increased Patient Choice and Engagement for AF Stroke Prevention) to evaluate its effectiveness in 1,200 participants. METHODS: Participants will be randomized to either usual care or to a SDM pathway incorporating a digital tool designed to simplify the complex concepts surrounding AF in conjunction with a clinician tool and a non-clinician navigator to guide the participants through each step of the tool. The participant-determined primary outcome for this study is the Decisional Conflict Scale, measured at 1 month after the index visit during which a decision was made regarding anticoagulation use. Secondary outcomes at both 1 and 6 months will include other decision making related scales as well as participant and clinician satisfaction, oral anticoagulation adherence, and a composite rate of major bleeding, death, stroke, or transient ischemic attack. The study will be conducted at four sites selected for their ability to enroll participants of varying racial and ethnic backgrounds, health literacy, and language skills. Participants will be followed in the study for 6 months. CONCLUSIONS: The results of the ENHANCE-AF trial will determine whether a decision aid facilitates high quality shared decision making in anticoagulation discussions for stroke reduction in AF. An improved shared decision-making experience may allow patients to make decisions better aligned with their personal values and preferences, while improving overall AF care.