Prior Atrial Fibrillation Research Articles

Many Models, Little Adoption-What Accounts for Low Uptake of Machine Learning Models for Atrial Fibrillation Prediction and Detection?

(1) Background: Atrial fibrillation (AF) is a major risk factor for stroke and is often underdiagnosed, despite being present in 13-26% of ischemic stroke patients. Recently, a significant number of machine learning (ML)-based models have been proposed for AF prediction and detection for primary and secondary stroke prevention. However, clinical translation of these technological innovations to close the AF care gap has been scant. Herein, we sought to systematically examine studies, employing ML models to predict incident AF in a population without prior AF or to detect paroxysmal AF in stroke cohorts to identify key reasons for the lack of translation into the clinical workflow. We conclude with a set of recommendations to improve the clinical translatability of ML-based models for AF. (2) Methods: MEDLINE, Embase, Web of Science, Clinicaltrials.gov, and ICTRP databases were searched for relevant articles from the inception of the databases up to September 2022 to identify peer-reviewed articles in English that used ML methods to predict incident AF or detect AF after stroke and reported adequate performance metrics. The search yielded 2815 articles, of which 16 studies using ML models to predict incident AF and three studies focusing on ML models to detect AF post-stroke were included. (3) Conclusions: This study highlights that (1) many models utilized only a limited subset of variables available from patients' health records; (2) only 37% of models were externally validated, and stratified analysis was often lacking; (3) 0% of models and 53% of datasets were explicitly made available, limiting reproducibility and transparency; and (4) data pre-processing did not include bias mitigation and sufficient details, leading to potential selection bias. Low generalizability, high false alarm rate, and lack of interpretability were identified as additional factors to be addressed before ML models can be widely deployed in the clinical care setting. Given these limitations, our recommendations to improve the uptake of ML models for better AF outcomes include improving generalizability, reducing potential systemic biases, and investing in external validation studies whilst developing a transparent modeling pipeline to ensure reproducibility.

Prior history of atrial fibrillation and arrhythmic outcomes: Data from the WEARIT-II prospective registry.

Wearable cardioverter defibrillator (WCD)is utilized in patients with assumed but not yet confirmed risk for sudden cardiac death (SCD).Many of these patients also present with atrial fibrillation (AF).However, the rate of WCD-detected ventricular or atrial arrhythmia events in this specific high-risk cohort is not well understood. In WEARIT-II,the cumulative probability of any sustained or nonsustained VT/VF(WCD-treatedand nontreated), and atrial/supraventricular arrhythmias during WCD use was assessed using the Kaplan-Meier method by prior AF, with comparisons by the log-rank test. The incidence of ventricular and atrial arrhythmia events were expressed as events per 100 patient-years, and were analyzed by prior AF using negative binomial regression. WEARIT-IIenrolled 2000 patients, 557 (28%) of whom had AF before enrollment. Cumulative probability of any sustained or nonsustained WCD-detected VT/VFduring WCD use was significantly higher among patients with a history of AF than without AF (6% vs. 3%, p = .001). Similarly, the recurrent rate of any sustained or nonsustained VT/VFwas significantly higher in patients with prior AF versus no prior AF (131.5 events per 100 patient-years vs. 22.7 events per 100 patient-years, p = .001). Patients with prior AF also had a significantly higher burden of any WCD-detected atrial arrhythmias/SVT/inappropriate arrhythmiastherapy (183.2 events per 100 patient-years vs. 74.8 events per 100 patient-years, p < .001). Our results demonstrate that patients with a history of AF wearing the WCD for risk assessment have a higher incidence of ventricular arrhythmias that may facilitate the decision making for ICD implantation.

A Practical Approach to the Management of Residual Cardiovascular Risk: United Arab Emirates Expert Consensus Panel on the Evidence for Icosapent Ethyl and Omega-3 Fatty Acids.

Patients with hyperlipidemia treated with statins remain at a residual cardiovascular (CV) risk. Omega-3 polyunsaturated fatty acids hold the potential to mitigate the residual CV risk in statin-treated patients, with persistently elevated triglyceride (TG) levels. We reviewed the current evidence on the use of icosapent ethyl (IPE), an omega-3 fatty acid yielding a pure form of eicosapentaenoic acid. REDUCE-IT reported a significant 25% reduction in CV events, including the need for coronary revascularization, the risk of fatal/nonfatal myocardial infarction, stroke, hospitalization for unstable angina, and CV death in patients on IPE, unseen with other omega-3 fatty acids treatments. IPE was effective in all patients regardless of baseline CV risk enhancers (TG levels, type-2 diabetes status, weight status, prior revascularization, or renal function). Adverse events (atrial fibrillation/flutter) related to IPE have occurred mostly in patients with prior atrial fibrillation. Yet, the net clinical benefit largely exceeded potential risks. The combination with other omega-3 polyunsaturated fatty acids, in particular DHA, eliminated the effect of EPA alone, as reported in the STRENGTH and OMEMI trials. Adding IPE to statin treatment seems to be cost-effective, especially in the context of secondary prevention of CVD, decreasing CV event frequency and subsequently the use of healthcare resources. Importantly, IPE has been endorsed by 20 international medical societies as a statin add-on treatment in patients with dyslipidemia and high CV risk. Robust medical evidence supports IPE as a pillar in the management of dyslipidemia.

Incidence and patterns of atrial fibrillation after catheter ablation of typical atrial flutter-the FLUTFIB study.

In patients with atrial flutter (AFL), ablation of the cavotricuspid isthmus (CTI) is a highly effective procedure to prevent AFL recurrence, but atrial fibrillation (AF) may occur during follow-up. The presented FLUTFIB study was designed to identify the exact incidence, duration, timely occurrence, and associated symptoms of AF after CTI ablation using continuous cardiac monitoring via implantable loop recorders. One hundred patients with AFL without prior AF diagnosis were included after CTI ablation (mean age 69.7 ± 9.7 years, 18% female) and received an implantable loop recorder for AF detection. After a median follow-up of 24 months 77 patients (77%) were diagnosed with AF episodes. Median time to first AF occurrence was 180 (43-298) days. Episodes lasted longer than 1 h in most patients (45/77, 58%). Forty patients (52%) had AF-associated symptoms.Patients with and without AF development showed similar baseline characteristics and neither HATCH- nor CHA2DS2-VASc scores were predictive of future AF episodes. Oral anticoagulation (OAC) was stopped during FU in 32 patients (32%) and was re-initiated after AF detection in 15 patients (15%). No strokes or transient ischaemic attack episodes were observed during follow-up. This study represents the largest investigation using implantable loop recorders (ILRs) to detect AF after AFL ablation and shows a high incidence of AF episodes, most of them being asymptomatic and lasting longer than 1 h. In anticipation of trials determining the duration of AF episodes that should trigger OAC initiation, these results will help to guide anticoagulation management after CTI ablation.

Assessing the impact of atrial fibrillation on symptoms and quality of life in hypertrophic cardiomyopathy.

In hypertrophic cardiomyopathy (HCM), atrial fibrillation (AF) has historically been regarded to have a deleterious impact on clinical course, strongly associated with progressive heart failure (HF) symptoms. However, there is a paucity of information regarding the impact of AF on HCM employing validated quality of life (QoL) surveys. Therefore, we evaluated the impact of AF on QoL utilizing patient reported outcome measures (PROMs). 218 consecutive HCM patients with or without AF at the Lahey HCM center in 2022 completed PROMs at their most recent visit evaluating HF (Kansas City Cardiomyopathy Questionnaire [KCCQ]) and AF symptoms (AF Effect on QoL [AFEQT]). Among the 218 patients, 50 (23%) had a history of AF and comprise the primary study cohort. AF was diagnosed at 55 ± 10 years of age, median of 5.5 years before PROM, with 66% of patients treated with a rhythm control strategy with antiarrhythmic drug and/or AF ablation. AFEQT indicated that 52% of patients experienced no or minimal AF-related disability, mild to moderate in 22%, and severe in 26%. There was no substantial difference in HCM phenotype in patients with no or minimal AF disability compared to those with severe disability. HF symptoms for most HCM patients with prior AF history was consistent with no or minimal (59%) or only mild (27%) disability as measured by KCCQ overall summary scores. In addition, with multivariate analysis, AF history was associated with less HF symptoms and improved QoL (OR 0.4, p = 0.02). In contrast to prior perceptions, HCM patients with prior AF history were less likely to incur HF symptoms impairing QoL compared to HCM patients without AF. After treatment, prior history of AF did not substantially impact current QoL. These data provide a realistic appraisal for the impact that AF has on HCM patients and also offers a measure of reassurance for this patient subgroup.

Day-to-day home blood pressure variability and risk of atrial fibrillation in a general Japanese population: the Hisayama Study.

Several prospective studies have reported that higher visit-to-visit blood pressure variability (BPV) is associated with atrial fibrillation (AF). However, no studies have investigated the association between day-to-day BPV assessed by home blood pressure measurement and the development of AF. A total of 2829 community-dwelling Japanese aged ≥40 years without prior AF were followed up for 10 years (2007-17). Day-to-day home BPV [defined as coefficient of variation (CoV) of home systolic blood pressure (SBP) for 28 days] was categorized into four groups according to the quartiles: Q1, ≤ 4.64%; Q2, 4.65-5.70%; Q3, 5.71-7.01%; Q4, ≥ 7.02%. The hazard ratios for developing AF were estimated using a Cox proportional hazards model. During the follow-up period, 134 participants developed new-onset AF. The crude incidence rates of AF increased significantly with higher CoV levels of home SBP: 2.1, 4.9, 5.2, and 8.8 per 1000 person-years in the first, second, third, and fourth quartiles, respectively (P for trend < 0.01). After adjusting for potential confounders, increased CoV levels of home SBP were associated significantly with a higher risk of AF (P for trend = 0.02). The participants in the highest quartile of CoV had a 2.20-fold (95% confidence intervals: 1.18-4.08) increased risk of developing AF compared with those in the lowest quartile. The present findings suggest that increased day-to-day home BPV levels are associated with a higher risk of the development of AF in a general Japanese population.

Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis of clinical trials.

Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in a variety of settings. This study aimed to assess whether cardioprotective effects of MRAs are modified by heart failure (HF) and atrial fibrillation (AF) status and to study their impact on AF events. MEDLINE, Embase, and Cochrane Central databases were searched to 24 March 2023 for randomized controlled trials evaluating the efficacy of MRAs as compared with placebo or usual care in reducing cardiovascular outcomes and AF events in patients with or at risk for cardiovascular diseases. Random-effects models and interaction analyses were used to test for effect modification. Meta-analysis of seven trials (20 741 participants, mean age: 65.6 years, 32% women) showed that the efficacy of MRAs, as compared with placebo, in reducing a composite of cardiovascular death or HF hospitalization remains consistent across patients with HF [risk ratio = 0.81; 95% confidence interval (CI): 0.67-0.98] and without HF (risk ratio = 0.84; 95% CI: 0.75-0.93; interaction P = .77). Among patients with HF, MRAs reduced cardiovascular death or HF hospitalization in patients with AF (hazard ratio = 0.95; 95% CI: 0.54-1.66) to a similar extent as in those without AF (hazard ratio = 0.82; 95% CI: 0.63-1.07; interaction P = .65). Pooled data from 20 trials (21 791 participants, mean age: 65.2 years, 31.3% women) showed that MRAs reduce AF events (risk ratio = 0.76; 95% CI: 0.67-0.87) in both patients with and without prior AF. Mineralocorticoid receptor antagonists are similarly effective in preventing cardiovascular events in patients with and without HF and most likely retain their efficacy regardless of AF status. Mineralocorticoid receptor antagonists may also be moderately effective in preventing incident or recurrent AF events.

Systematic Brain Natriuretic Peptide Measurement for Cardiac Screening in Patients with Severe Obesity: The OLECOEUR Study

Introduction: Heart failure (HF) is difficult to diagnose in obese patients because of cardiovascular and pulmonary comorbidities associated with physical deconditioning, all of which lead to dyspnea. Methods: The OLECOEUR study is a prospective screening for HF using systematic brain natriuretic peptide (BNP) measurement in ambulatory patients with obesity from a department of Nutrition (Paris, France). Clinical, biological, and echocardiographic data were extracted from electronic medical records. Results: We included 1,506 patients middle-aged (mean age: 47.2 ± 14.6 years old) with severe obesity (mean body mass index: 40.4 ± 6.6 kg/m2). Patients with BNP ≥35 pg/mL had left heart remodeling including thicker interventricular septum (10.4 ± 2.0 vs. 9.6 ± 1.8 mm; p = 0.0008), higher left ventricular mass (89.9 ± 24.3 vs. 77.2 ± 20.0 g/m2; p = 0.0009), and significant changes in both left and right atria consistent with a higher proportion of prior atrial fibrillation. Markers of right heart remodeling on echocardiography were also significantly higher (pulmonary artery systolic pressure: 33.3 ± 17.3 vs. 24.5 ± 6.3 mm Hg; p = 0.0002). Conclusion: The OLECOEUR study shows left and right subclinical cardiac remodeling in obese patients screened for HF with systematic dosing of BNP with usual cut-off of 35 pg/mL.

Clinical Outcomes in Hospitalized Patients with Cancer and New versus Preexistent Atrial Fibrillation.

There is limited information on the prognostic impact of new onset versus preexistent atrial fibrillation (AF) in hospitalized patients with cancer. We sought to determine the clinical impact of new onset AF (NOAF) compared with preexistent AF in hospitalized patients with cancer. All patients with cancer hospitalized over the course of one year with clinically manifest new or preexistent AF were enrolled in the Memorial Sloan Kettering Cancer Center (MSKCC) AF registry. The relationship of NOAF to the primary composite outcome of all cause death, cardiovascular (CV) rehospitalization or cerebrovascular event (CVE), as well as secondary CV endpoints, were analyzed using proportional hazards regression. Where applicable, the competing risk of death was accounted for using methodology described by Fine and Gray. Among 606 patients included in the analysis, 313 (51.7%) had NOAF and 293 (48.3%) had preexistent AF. Patients with NOAF were younger and had less frequent prior history of CV disease compared with patients with preexistent AF. At follow up, patients with NOAF had a higher adjusted hazard for the primary composite outcome versus patients with prior AF (HR 1.64, 95% CI 1.27, 2.13, p=0.002), as well as the secondary CV composite outcome of clinical AF recurrence, CV death, CV rehospitalization or CVE (HR 2.17, 95% CI 1.57, 2.99, P<0.0001). In hospitalized patients with cancer and electrocardiographically manifest new versus preexistent AF, NOAF was associated with a higher risk for the primary composite outcome of all-cause death, CV rehospitalization or CVE.

Impact of Baseline Comorbidities and Treatment on Cardiovascular (CV) Outcomes in Patients with Chronic Lymphocytic Leukemia (CLL): Results of a Systematic Literature Review (SLR) of Interventional Trials and a Targeted Literature Review (TLR) of Real-World Observational Studies in CLL

Background: Ibrutinib, the first Bruton tyrosine kinase inhibitor (BTKi) indicated for CLL, has been associated with a higher risk of CV events, including atrial fibrillation (AF) and hypertension, vs non-BTKi active comparators and placebo. In a phase 3 clinical trial of patients (pts) with CLL comparing ibrutinib with acalabrutinib-a more selective, second-generation BTKi-CV event incidence was numerically higher with ibrutinib and the incidence and cumulative risk of AF were significantly higher with ibrutinib (Byrd JC et al. J Clin Oncol. 2021;39:3441-52). Ibrutinib's toxicity profile prompted changes to its prescribing information and lowered its recommendation status in current CLL guidelines. We conducted an SLR of interventional trials in CLL followed by a supplemental TLR of observational studies in CLL to explore the extent to which CV outcomes of pts with CLL are driven by their baseline comorbidities or treatments. Methods: Embase and MEDLINE were searched to identify evidence in peer-reviewed journals (cutoff date: June 23, 2023). For the SLR, limits were English articles published in 2012 or later, and inclusion criteria specified phase 2/3 interventional trials in adults aged ≥18 y with treatment-naive or relapsed/refractory CLL. Treatments included BTKis, BCL-2 inhibitors, and chemoimmunotherapy. CV outcomes were arrhythmia, heart failure, major adverse CV events, major bleeding, myocardial infarction, stroke, sudden cardiac death, and venous thromboembolism. For the TLR, language and time limits were analogous to the SLR. Additional limits were observational studies with &amp;gt;70% CLL pts receiving any or no treatment. The TLR assessed baseline CV events/risk, including arrhythmia, heart failure, major adverse CV events, major bleeding, myocardial infarction, stroke, sudden cardiac death, and venous thromboembolism. Results: The SLR yielded 55 studies. Among the phase 3 randomized controlled trials, incidence ranges were 0%-16% for AF/atrial flutter, 0%-6.9% for heart failure, and 0%-11% for major bleeding; rates were generally higher with BTKis, among which ibrutinib appeared to be associated with the highest rates ( Figure 1). CV data from the SLR were sparse and heterogeneous, primarily due to limited baseline CV risk reporting and substantial variability in CV adverse event reporting. To clarify relationships of CV risk with treatment, we performed the TLR, which yielded 24 studies. Analysis of baseline CV risk reported in the observational studies yielded several key findings ( Figure 2): 1) in pts with CLL, the risk of CV events, including AF, increased with age; in pts aged 65−74 y and ≥65 y, the reported risk of AF was 2.4-fold and 2.8-fold higher, respectively, than that of pts aged &amp;lt;65 y (Shanafelt TD et al. Leuk Lymphoma. 2017;58:1630-9; Visentin A et al. Hematol Oncol. 2019;37:508-12); 2) baseline CV risk was similarly high in pts with CLL and matched non-CLL comparators (Larsson K et al. Am J Hematol. 2022;97:E255-7); 3) ibrutinib was associated with a higher risk of CV disease relative to chemotherapy, even when prior AF, age, and anticoagulant exposure were controlled for (Abdel-Qadir H et al. J Clin Oncol. 2021;39:3453-62). In ibrutinib-treated pts with a B-cell malignancy followed in cardio-oncology clinics (N=53; n=38 CLL), median time to new onset of ibrutinib-related AF was 5.5 mo; AF incidence was 15-fold higher in ibrutinib-treated pts overall vs that expected in an age- and sex-comparable general population and in ibrutinib-treated pts with CLL vs that expected in pts with CLL and no ibrutinib treatment (Baptiste F et al. Open Heart. 2019;6:e001049). Conclusions: CLL primarily affects the elderly, who are at higher risk of CV events vs a younger demographic. Results suggest that some pts with CLL have an increased risk of adverse CV outcomes; thus, it would be inaccurate to attribute the higher rates of CV events observed in pts with CLL solely to their treatment as it is plausible that pts with CLL already have an elevated CV risk contributing to such outcomes. However, our findings suggest that the first-generation BTKi (ibrutinib) may impact CV outcomes in these pts; data examining the CV risk of second-generation BTKis and other novel therapies (eg, venetoclax) are limited. Future research that consistently estimates baseline CV risk and closely monitors CV parameters in pts with CLL is required to ascertain the true risk of CV disease due to CLL treatment.

Multimorbidity in atrial fibrillation for clinical implications using the Charlson Comorbidity Index

BackgroundPredicting survival in atrial fibrillation (AF) patients with comorbidities is challenging. This study aimed to assess multimorbidity in AF patients using the Charlson Comorbidity Index (CCI) and its clinical implications. MethodsWe analyzed 451,368 participants from the Korea National Health Insurance Service-Health Screening cohort (2002−2013) without prior AF diagnoses. Patients were categorized into new-onset AF and non-AF groups, with a high CCI defined as ≥4 points. Antithrombotic treatment and outcomes (all-cause death, stroke, major bleeding, and heart failure [HF] hospitalization) were evaluated over 9 years. ResultsIn total, 9.5% of the enrolled patients had high CCI. During follow-up, 12,241 patients developed new-onset AF. Among AF patients, antiplatelet drug use increased significantly in those with high CCI (adjusted odds ratio [OR] 1.05, 95%confidence interval [CI] 1.02–1.08, P < .001). However, anticoagulants were significantly less prescribed in patients with high CCI (OR 0.97, 95%CI 0.95–0.99, P = .012). Incidence of adverse events (all-cause death, stroke, major bleeding, HF hospitalization) progressively increased in this order: low CCI without AF, high CCI without AF, low CCI with AF, and high CCI with AF (all P < .001). Furthermore, high CCI with AF had a significantly higher risk compared to low CCI without AF (all-cause death, adjusted hazard ratio [aHR] 2.52, 95% CI 2.37–2.68, P < .001; stroke, aHR 1.43, 95% CI 1.29–1.58, P < .001; major bleeding, aHR 1.14, 95% CI 1.04–1.26, P = .007; HF hospitalization, aHR 4.75, 95% CI 4.03–5.59, P < .001). ConclusionsHigh CCI predicted increased antiplatelet use and reduced oral anticoagulant prescription. AF was associated with higher risks of all-cause death, stroke, major bleeding, and HF hospitalization compared to high CCI.

Frequency and risk factors of atrial fibrillation after acute abdominal surgery: A prospective cohort study.

Scarce data exist on the true incidence of postoperative atrial fibrillation (POAF) after acute abdominal surgery and associated outcomes. The current study aimed to identify the frequencies of clinically recognized POAF and associated complications, along with their risk factors. This study was a prospective, single-center cohort study of unselected adult patients referred for acute abdominal surgery during a 3-month period. Through careful review, demographics, comorbidity, and surgical characteristics were prospectively drawn from medical charts. The primary outcome was clinically recognized POAF occurring in-hospital. Logistic regression was used to determine the risk factors of POAF and associated complications. A subgroup was enrolled in a feasibility study of peri- and postoperative continuous cardiac rhythm monitoring. In total, 450 patients were enrolled. Clinically recognized in-hospital POAF was observed in 22 patients (4.9%). All cases were observed in patients aged ≥60 years, corresponding to 22 of 164 patients (13.4%). Multiple risk factors were observed, such as age, prior atrial fibrillation, heart failure, hypertension, diabetes mellitus, chronic renal disease, and major (vs. minor) surgery. POAF was associated with severe in-hospital complications (POAF group 45.5% vs. non-POAF group 8.6%, p < .001) and in-hospital mortality (POAF group 13.6% vs. non-POAF group 3.0%, p = .043). In total, 295 patients were monitored by continuous cardiac rhythm monitoring for 12,148 h, yielding five patients with asymptomatic AF. In conclusion, this prospective study of POAF in patients undergoing acute abdominal surgery showed that one in 20 patients developed clinically recognized in-hospital POAF. Multiple risk factors of POAF were identified. POAF was associated with severe complications up to 30 days after surgery.

Left atrial mechanical dysfunction and the risk for ischemic stroke in HCM patients without prior atrial fibrillation or stroke

Abstract Background Patients with hypertrophic cardiomyopathy (HCM) are at high risk of atrial fibrillation (AF) and ischemic stroke. Left atrial enlargement and dysfunction that characterize atrial myopathy may precede and promote AF and cardiac thromboembolism. In HCM patients without prior AF or stroke, whether left atrial mechanical dysfunction can improve ischemic stroke prediction is unknown. Method Patients with prior AF or stroke (n = 121) were excluded and 653 consecutive patients with HCM (mean age 47.3 ± 12.3 years, 71% male) who underwent cardiac magnetic resonance (CMR) at Fuwai Hospital between January 2012 and December 2013 were finally enrolled. LA ejection fraction, strain and strain rate indices on reservoir, conduit and booster-pump phases that represent LA mechanical function were analyzed. The primary endpoint was ischemic stroke. The secondary endpoint was new-onset AF. Result At 7.6 ± 2.4 years of follow-up, 24 (3.7%) had ischemic stroke and 73 (11.2%) had new-onset AF. Patients with stroke had an older age (p = 0.014), higher incidence of hypertension (p &amp;lt; 0.001), more LGE presence (p = 0.006) and LGE extent (p = 0.007). For LA size and function, patients with stroke showed significantly higher LA volume index and lower LA ejection fraction and LA strain (all p &amp;lt; 0.01). Age, hypertension, LGE presence, LGE extent and all LA mechanical indices were univariably associated with stroke. On multivariate model, LA reservoir strain was associated with stroke (Hazard Ratio = 0.91. 95%CI 0.85-0.97, p = 0.005) independent of Age (p = 0.292), hypertension (p = 0.002), LGE extent (p = 0.003) and LA volume (p = 0.737). In addition, LA reservoir strain was also associated with new-onset AF (Hazard Ratio = 0.93. 95%CI 0.89-0.96, p &amp;lt; 0.001) independent of Age (p &amp;lt; 0.001), hypertension (p = 0.607), LGE extent (p = 0.882) and LA volume (p = 0.002). Conclusion In HCM patients without prior AF or stroke, LA mechanical dysfunction was a strong predictor for stroke and new-onset AF independent of LA enlargement, age, hypertension and LGE extent.

Five-year changes in weight and risk of atrial fibrillation in women and men from the Danish diet, cancer, and health cohort

Abstract Background Overweight and obesity are causal risk factors for atrial fibrillation (AF).(1) Mendelian randomization studies indicated a higher risk of AF with each unit increase in body mass index (BMI).(1) In observational studies, weight gain was associated with a higher risk of incident AF compared to stable weight.(2,3) However, the results are conflicting regarding the association between weight loss and risk of incident AF.(4,5). Purpose We aimed to assess the association between five-year changes in weight and absolute and relative rates of incident AF in women and men from the Danish Diet, Cancer, and Health Cohort. Methods In the Danish cohort study Diet, Cancer, and Health, participants were invited to attend a recruitment research examination and a second examination 5 years later. Height, weight, and several lifestyle factors were assessed at both examinations. We calculated BMI and BMI changes between first and second examination. BMI changes were categorized into following groups: &amp;lt;-5 kg/m2, ≥-5 to &amp;lt;-2.5 kg/m2, ≥-2.5 to &amp;lt;2.5 kg/m2, ≥2.5 to &amp;lt;5 kg/m2 and ≥5 kg/m2. Diagnoses of AF and comorbidities were retrieved from the Danish National Patient Registry. We used multivariable-adjusted Cox proportional hazards models to assess hazard ratios (HR) of AF according to changes in BMI. Results 43,758 participants without prior AF were included in the study. The median age was 62 (25th-75th percentile, 58-66) years and 54% were women. Over 15.7 years median follow-up time 5,312 participants had incident AF. From the first to the second measure, 39,076 (89%) of participants had stable weight, 2,627 (6%) lost weight, and 2,055 (5%) gained weight. The incidence rates of AF per 1,000 person-years were 8.4 (95% CI 8.1-8.6) among participants with stable weight, 12.4 (95% CI 9.6-16.1) among those with weight loss ≥5 kg/m2, and 15.4 (95% CI 11.7-20.2) among those who gained ≥5 kg/m2. Compared to participants with stable weight, individuals who gained ≥2.5 to &amp;lt;5 kg/m2 had a higher hazard of AF (HR 1.24, 95% CI 1.09-1.41). Among participants who gained ≥5 kg/m2 the rate of AF was also higher compared to stable weight (HR 1.95, 95% CI 1.48-2.56). There was no statistically significant association between weight loss, regardless of degree, and rate of AF. Figure 1 shows the HR of AF by BMI changes from first to second measure compared to stable weight using restricted cubic splines. In sex-stratified analyses, the association between weight gain of ≥5 BMI units (kg/m2) and higher AF rate was present for both women and men. Conclusions In this cohort study, five-year weight gain was associated with higher long-term risk of AF compared to stable weight. However, we found no associations between weight loss and long-term risk of AF.Figure 1

Echocardiographic characterization of patients with supranormal ejection fraction: pooled core laboratory analysis of the TOPCAT and PARAGON-HF trials

Abstract Background Patients with heart failure and supranormal ejection fraction (HFsnEF) may be phenotypically distinct from those with normal or below normal left ventricular ejection fraction (LVEF), and may demonstrate different prognostic trajectories or treatment responses. Purpose To characterize clinical features, cardiac structure and function among patients with HF with preserved EF (defined as 45% ≤ LVEF ≤ 65%) and supranormal EF (defined as LVEF&amp;gt;65%). Methods Baseline clinical characteristics and key echocardiographic parameters from patients enrolled in the echocardiographic substudies of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist)-Americas and PARAGON-HF (Prospective Comparison of ARNI [angiotensin receptor–neprilysin inhibitor] with ARB [angiotensin-receptor blocker] Global Outcomes in Heart Failure with Preserved Ejection Fraction) were compared between patients with and without HFsnEF. Results Among 1,751 participants (mean age 73 years old, 51% women) in this pooled core laboratory analysis, 265 (15%) had HFsnEF. Participants in HFsnEF group were more likely to be women, and less likely to have prior myocardial infarction and atrial fibrillation (Table 1). Compared with those with LVEF ≤ 65%, those with LVEF &amp;gt; 65% had lower LV end-diastolic and end-systolic volume indices, lower LV mass index, higher LV relative wall thickness, and higher right ventricular fractional area change. LV geometry and measures of LV diastolic function were similar in both groups (Table 1). Global longitudinal strain (GLS) was abnormal (absolute GLS &amp;lt;16%) in 28% in those with HFsnEF compared with 53% in those with LVEF ≤ 65%. After adjusting for baseline LV ejection fraction and sex, and stratified by trial, abnormal GLS was associated with a higher risk of composite of first heart failure hospitalization or cardiovascular death (overall hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.23 – 1.98, P &amp;lt; 0.001), cardiovascular death (overall HR 2.06, 95% CI 1.35 – 3.13, P = 0.001), and heart failure hospitalization (overall HR 1.49, 95% CI 1.15 – 1.93, P = 0.003) in both HFsnEF and non-HFsnEF groups (P-interaction &amp;gt; 0.05 for all, Figure 1). Conclusions Among participants in the TOPCAT-Americas and PARAGON-HF trials, those with LVEF &amp;gt; 65% were predominantly women, had less LV remodeling, and had better RV function based on echocardiographic measures. Nevertheless, despite supranormal LVEF, GLS was abnormal in over a quarter of patients and remained an important predictor of adverse clinical outcomes in this cohort.Table 1Figure 1

Lower risk of atrial fibrillation development associated with SGLT-2 inhibitors in type 2 diabetic patients compared to DPP-4 inhibitors: a nationwide cohort study

Abstract Background Accumulating evidence shows that sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduce cardiovascular outcomes. However, this favorable effect is unclear for newly atrial fibrillation (AF) development compared to other anti-diabetic drugs. Purpose We investigated the association of SGLT-2 inhibitor for newly AF development compared to dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes. Methods Using the Korean National Health Insurance Service database, among 2,160,911 type 2 diabetes patients (age ≥20 years) between 1 May 2016 and 31 December 2018, we studied 42,806 patients with SGLT-2 inhibitors and 448,715 patients with DPP-4 inhibitors who had not prior AF diagnosis. Propensity score-matching (1:1 ratio) was used to correct for differences between the groups. Results During a median follow-up of 1.3 years, after propensity score matching, compared with patients with DPP-4 inhibitors (n=42,786), patients with SGLT-2 inhibitors (n=42,786) have shown lower incidence and risk of AF (2.7 and 3.3 per 1000 person-years; hazard ratio 0.73, 95% confidence interval 0.55-0.97; p=0.028) aand an absolute rate difference of −0.7 [95% confidence interval (CI) −1.3 to −0.1, p=0.034] per 1000 person-years by on-treatment analysis. In intention-to-treat analysis, these results were consistent (2.6 and 3.2 per 1000 person-years; hazard ratio 0.83, 95% confidence interval 0.66-1.03; p=0.092) with an absolute rate difference of −0.5 [95% confidence interval (CI) −1.2 to −0.1, p=0.093] per 1000 person-years . In subgroup analysis, SGLT-2 inhibitors were associated with lower risks of AF in heart failure compared to their counterparts in intention-to-treat analysis (p for interaction=0.036). Conclusion Based on this nationwide cohort of type 2 diabetes patients treated with SGLT-2 inhibitors or DPP-4 inhibitors, SGLT-2 inhibitors were associated with protection against newly AF development after adjusting for clinical confounders.Incidence rates and adjusted HR

Abstract 14968: Clonal Hematopoiesis and Cardiotoxic Risk After Hematopoietic Stem Cell Transplantation

Background: Clonal hematopoiesis (CH) occurs as part of normal hematopoietic stem cell senescence and prior chemotherapy administration. As such, CH is frequent for patients undergoing allogeneic stem cell transplants (ASCT). CH has been identified as a driver of inflammation. In animals, inflammation plays a role in atrial fibrillation (AF) development, the most common cardiotoxicity after ASCT treatment. Yet, whether the presence of post-ASCT CH associates with AF risk is unknown. Methods: We analyzed bone marrow derived mononuclear cells from 201 cancer patients treated with ASCT by deep targeted amplicon sequencing (next generation sequencing) to detect the presence of select CH (defined as DNMT3A, TET2, ASXL1, IDH1, FLT3, JAK2 at VAF of ≥ 2%), irrespective of relapse status; at median 4 months post ASCT. Observed incident AF rates were compared to Framingham heart predicted rates. Cox regression and survival analysis were used to define factors associated with incident AF and MACE, as well as the relationship between the presence of post-transplant CH mutations and MACE risk. Further, we also assessed the effect of CH on post-ASCT survival outcomes. The presence of mutations was analyzed for an association with post-ASCT incident AF and overall survival. Results: Overall, the prevalence of CH in post-ASCT patients was 42.3% (85), including 29.5% with ≥2 mutations. Over a median follow-up of 33 months, 11.5% of patients developed incident AF and 29.9% experienced MACE. In those without prior AF, the weighted average incidence was 407/10,000 person-years compared to the Framingham-predicted 63/10,000 person-years (RR 6.4, P &lt;0.001; AER 344). In follow-up, increased CH burden associated with increased risk of incident AF (HR 3.6, P =0.04), cancer-progression (HR 2.6, P =0.006), and mortality (HR 2.09, P =0.047); Figure . There was no difference in non-AF MACE. Conclusions: The presence of CH in ASCT treated cancer patients appears to associate with increased AF risk.

Abstract 15998: Impact of Atrial Fibrillation Detected by Cardiac Implantable Electronic Devices on Embolic Stroke Events in Cancer Patients

Background: Cancer patients have a higher risk of atrial fibrillation (AF) than general population, however, the link between cancer and AF is not fully understood. The association between AF detected by implanted cardiac implantable electronic devices (CIEDs) and the incidence of embolic stroke events has been reported. However, little is known about the incidence of AF and embolic stroke events in Japanese cancer patients with CIEDs. Moreover, the cut-off value of new-onset AF duration detected by CIEDs for embolic stroke is still unknown, and a problem to be solved in the future. The aim of this study is to identify the incidence of embolic stroke in Japanese cancer patients with a CIED and to examine the risk factors of embolic stroke. Methods: We retrospectively analyzed the database of our CIEDs clinic. Every 6 months, AF events were checked by CIEDs. Patients who had a history of AF or had received anticoagulant therapies before a CIED implantation and who are prescribed anticoagulants after a CIED implantation were excluded. We examined the characteristics and incidence of embolic stroke events and investigated the relationship between new-onset AF detected by CIEDs and the incidence of embolic stroke. Results: We enrolled 138 consecutive cancer patients with CIEDs who had no prior AF and took no anticoagulant in this study (follow-up period, 76±48 months; age, 73±16 years). During the follow-up period, 13 patients (9.4%) had embolic stroke events. Receiver-operating characteristic curve analysis confirmed that 20 seconds was the best cut-off value of AF duration detected by CIEDs for embolic stroke events (AUC = 0.75). Multivariate analysis demonstrated that independent predictors for embolic stroke were left atrial diameter ≥ 40mm (P=0.018) and new-onset AF ≥ 20 seconds (P = 0.0082). Conclusions: AF episodes lasting for ≥ 20 seconds and enlarged left atrium were the risk factors of embolic stroke events. We consider examining AF burden carefully in this population.

Abstract 16332: Atrial Fibrillation Monitoring in Patients on Ibrutinib

Introduction: Ibrutinib increases risk of atrial and ventricular arrythmias, especially atrial fibrillation (AF). No guidelines exist for arrhythmia monitoring, but experts suggest 24h Holter assessments for patients at risk of new or recurring AF or with CHA2DS2-VASc score ≥2. We sought to describe current practices in cardiac event monitoring in high risk or symptomatic patients on ibrutinib. Methods: We performed a single-center retrospective analysis of 168 ibrutinib-treated patients with no prior AF or atrial flutter (AFL). Patients were followed from 2013 to 2022. Event monitor data was obtained by a single reviewer through chart review. Results: Among 168 patients followed over a median of 6.4 years, 44 developed AF/AFL (25%) with 31 (70%) with paroxysmal AF. Mean (SD) age at ibrutinib initiation was 66 (11.1) years. Fewer than half (n=50; 30%) were female. Event monitoring was performed for 31 (18.4%) patients, 18 (58%) during treatment and 13 (42%) after treatment completion ( Table 1 ). The most common monitoring reasons were palpitations (10, 32%) and assessing AF burden (9, 29%). Cardiologists outside electrophysiology and cardio-oncology ordered the most monitors (17, 55%). Monitors most captured unspecified SVT (11, 36%) or no significant findings (9, 29%). Monitors most likely resulted in no management changes (19, 61%). The most common management changes were: placement of DC-PM (3, 10%), discontinuing anticoagulation (AC) (3, 10%) and diagnosis of AF (3, 10%). Of note, 14 monitors were done after AF diagnosis of which 7 (50%) showed no AF. Conclusions: Even with increased risk of arrythmias, use of monitors was low across a cohort of 168 patients. Notably, 3 monitors were used to discontinue AC and 3 monitors found new AF. Recent studies show most AF/AFL in ibrutinib users occurs within the first 6 months of initiation which may inform decisions in screening. Further guidance and standardization are needed for the use of monitors in the ibrutinib population.

Abstract 16426: A Risk Model to Predict Atrial Fibrillation in Diabetes Using Machine Learning: The ACCORD Study

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia seen in clinical practice, which necessitates identifying factors that can precipitate this dysrhythmia. We utilized the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial to build an AF risk prediction model specifically in the type 2 diabetes (T2DM) population, using machine learning (ML) approaches, and comparing to the established CHARGE-AF risk model. Methods: We utilized a patient cohort from the ACCORD clinical trial without prior AF. Baseline characteristics were collected as potential risk factors and incident AF was defined from ECG at follow-up. A random forest (RF) binary classifier was trained with 27 variables, including age, race, sex, smoking, waist circumference, BMI, blood pressure (BP), history of heart disease, medications, cholesterol, renal function, and left ventricular hypertrophy by ECG. All ACCORD subjects had T2DM, therefore this variable was not included. The CHARGE-AF model consisted of a Cox proportional hazard model trained on the following variables: age, race, height, weight, systolic/diastolic BP, current smoking, heart failure, prior MI, and BP medication. Area under ROC curve (AUC) was measured with randomized, stratified, 5-fold cross validation with 80/20 splits. Imputation and resampling methods were used for missing data and class imbalance. Results: Out of 9307 patients in the ACCORD cohort, 175 developed AF during the study period of 6.26 years, with a mean time to AF event of 3.68 years. The RF model, with an AUC of 0.912, showed improved prediction of AF over the Cox model, which had an AUC of 0.784. Permutation feature importance revealed age, race, waist circumference, weekly alcohol consumption, sex, and GFR as the most predictive features of the RF model (Fig 1). Conclusions: The CHARGE-AF risk model performed modestly on the ACCORD cohort, while a RF model showed superior performance.