Cumulative Incidence Of Atrial Fibrillation Research Articles

Atrial fibrillation incidence after coronary artery bypass graft surgery and percutaneous coronary intervention: the prospective AFAF cohort study

Objectives. Atrial fibrillation is a common arrhythmia in patients with ischemic heart disease. This study aimed to determine the cumulative incidence of new-onset atrial fibrillation after percutaneous coronary intervention or coronary artery bypass grafting surgery during 30 days of follow-up. Design. This was a prospective multi-center cohort study on atrial fibrillation incidence following percutaneous coronary intervention or coronary artery bypass grafting for stable angina or non-ST-elevation acute coronary syndrome. Heart rhythm was monitored for 30 days postoperatively by in-hospital telemetry and handheld thumb ECG recordings after discharge were performed. The primary endpoint was the cumulative incidence of atrial fibrillation 30 days after the index procedure. Results. In-hospital atrial fibrillation occurred in 60/123 (49%) coronary artery bypass graft and 0/123 percutaneous coronary intervention patients (p < .001). The cumulative incidence of atrial fibrillation after 30 days was 56% (69/123) of patients undergoing coronary artery bypass grafting and 2% (3/123) of patients undergoing percutaneous coronary intervention (p < .001). CABG was a strong predictor for atrial fibrillation compared to PCI (OR 80.2, 95% CI 18.1–354.9, p < .001). Thromboembolic stroke occurred in-hospital in one coronary artery bypass graft patient unrelated to atrial fibrillation, and at 30 days in two additional patients, one in each group. There was no mortality. Conclusion. New-onset atrial fibrillation during 30 days of follow-up was rare after percutaneous coronary intervention but common after coronary artery bypass grafting. A prolonged uninterrupted heart rhythm monitoring strategy identified additional patients in both groups with new-onset atrial fibrillation after discharge.

Five-year follow-up of a phase 2 study of ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial therapy in CLL

AbstractWe previously reported high rates of undetectable minimal residual disease <10−4 (uMRD4) with ibrutinib plus fludarabine, cyclophosphamide, and rituximab (iFCR) followed by 2-year ibrutinib maintenance (I-M) in treatment-naïve chronic lymphocytic leukemia (CLL). Here, we report updated data from this phase 2 study with a median follow-up of 63 months. Of 85 patients enrolled, including 5 (6%) with deletion 17p or TP53 mutation, 91% completed iFCR and 2-year I-M. Five-year progression-free survival (PFS) and overall survival were 94% (95% confidence interval [CI], 89%-100%) and 99% (95% CI, 96%-100%), respectively. No additional deaths have occurred with this extended follow-up. No difference in PFS was observed by immunoglobulin heavy-chain variable region gene status or duration of I-M. High rates of peripheral blood (PB) uMRD4 were maintained (72% at the end of iFCR, 66% at the end of 2-year I-M, and 44% at 4.5 years from treatment initiation). Thirteen patients developed MRD conversion without clinical progression, mostly (77%) after stopping ibrutinib. None had Bruton tyrosine kinase (BTK) mutations. One patient had PLCG2 mutation. Six of these patients underwent ibrutinib retreatment per protocol. Median time on ibrutinib retreatment was 34 months. The cumulative incidence of atrial fibrillation was 8%. Second malignancy or nonmalignant hematologic disease occurred in 13%, mostly nonmelanoma skin cancer. Overall, iFCR with 2-year I-M achieved durably deep responses in patients with diverse CLL genetic markers. Re-emergent clones lacked BTK mutation and retained sensitivity to ibrutinib upon retreatment. This trial is registered at www.clinicaltrials.gov as #NCT02251548.

Atrial fibrillation in patients with hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is associated with complications such as heart failure, atrial fibrillation (AF) and sudden cardiac death. The treatment of AF in HCM patients can be challenging since AF often aggravates symptoms and increases the risk of stroke. Little is known on which factors contribute to the development of AF in these patients. Purpose To determine the incidence of AF in Danish HCM patients and identify risk factors that increase risk of AF. Methods Using Danish national registers all patients without previous AF, aged 16 or older diagnosed with HCM between the 1st of January 2005, and the 31st of December 2018 were included in the analysis. The association between HCM and incident AF was investigated using multivariable Cox proportional-hazard analysis. Cumulative incidence of AF was calculated using the Aalen-Johansen estimator, taking death as a competing risk into account. Results A total of 3,200 HCM patients without prevalent AF were included, median age was 66 years (IQR 55-77) and 48% were female. During the study period, 477 (15%) patients were diagnosed with incident AF. The risk of developing AF was equal between genders and average time from HCM diagnosis to debut of AF was 1260 days. Risk of AF development was increased for patients with prevalent ischemic heart disease (HR 1.33, CI [1.08 – 1. 63]) and hypertension (HR 1.34, CI [1.11 – 1. 63]) as well as for patients classifies as obstructive HCM at diagnosis (HR 1.27, CI [1.06 – 1. 53]). Following AF diagnosis, prescription with oral anticoagulants and antiarrhythmic medication increased markedly. Conclusion AF is a common complication in HCM. Patients with obstructive HCM, hypertension and ischemic heart disease were at increased risk of developing AF.Figure 1:CI of AF by genderFigure 2:HR for AF developement

Incident Atrial Fibrillation and Survival Outcomes in Esophageal Cancer following Radiotherapy

Radiation therapy (RT) associates with long-term cardiotoxicity. In preclinical models, RT exposure induces early cardiotoxic arrhythmias including atrial fibrillation (AF). Yet, whether this occurs in patients is unknown. Leveraging a large cohort of consecutive patients with esophageal cancer treated with thoracic RT from 2007 to 2019, we assessed incidence and outcomes of incident AF. Secondary outcomes included major adverse cardiovascular events (MACE), defined as AF, heart failure, ventricular arrhythmias, and sudden death, by cardiac RT dose. We also assessed the relationship between AF development and progression-free and overall survival. Observed incident AF rates were compared with Framingham predicted rates, and absolute excess risks were estimated. Multivariate regression was used to define the relationship between clinical and RT measures, and outcomes. Differences in outcomes, by AF status, were also evaluated via 30-day landmark analysis. Furthermore, we assessed the effect of cardiac substructure RT dose (eg, left atrium, LA) on the risk of post RT-related outcomes. Overall, from 238 RT treated patients with esophageal cancer, 21.4% developed incident AF, and 33% developed MACE with the majority (84%) of events occurring ≤2 years of RT initiation (median time to AF, 4.1 months). Cumulative incidence of AF and MACE at 1 year was 19.5%, and 25.7%, respectively; translating into an observed incident AF rate of 824 per 10,000 person-years, compared with the Framingham predicted rate of 92 (relative risk, 8.96; P < .001, absolute excess risk 732). Increasing LA dose strongly associated with incident AF (P=.001); and those with AF saw worse disease progression (hazard ratio, 1.54; P=.03). In multivariate models, outside of traditional cancer-related factors, increasing RT dose to the LA remained associated with worse overall survival. Among patients with esophageal cancer, radiation therapy increases AF risk, and associates with worse long-term outcomes.

5‐YEAR (Y) FOLLOW‐UP OF A PHASE 2 STUDY OF IBRUTINIB PLUS FLUDARABINE, CYCLOPHOSPHAMIDE, RITUXIMAB (IFCR) AS INITIAL THERAPY FOR YOUNGER CLL PATIENTS (PTS)

Introduction: This frontline study investigates whether iFCR followed by 2Y ibrutinib (IBR) maintenance (I-M) could provide deep and durable responses in CLL irrespective of IGHV status. We previously reported high rates of bone marrow undetectable minimal residual disease (BM-uMRD) in both IGHV unmutated (U-IGHV, 83%) and mutated (M-IGHV, 82%) pts (Davids et al., Lancet Haematol, 2019). Here, we report updated data at a median follow-up of 63 months. Methods: In this phase 2 investigator-sponsored trial (NCT02251548), eligible pts received up to 6 cycles of iFCR followed by 2Y I-M. Pts with BM-uMRD after 2Y I-M had the option to stop IBR. MRD was assessed with multicolor flow at 10-4. Targeted NGS covering 97 genes was applied to peripheral blood (PB) samples at MRD recurrence. Results: 85 pts with a median age of 55Y (range 38–65) were treated, including 53% with U-IGHV and 6% with del17p and/or TP53MUT. 77 pts (91%) completed 2Y I-M. 20 pts continued IBR beyond 2Y I-M, including 13 with detectable MRD in BM or PB at 2Y. Safety was similar to our previous report; the cumulative incidence of atrial fibrillation was 8%, and second malignancy occurred in 11%, mostly non-melanoma skin cancer. Two pts (2%) had secondary myeloid neoplasms. No new deaths have occurred since the one death reported in the prior publication (sudden cardiac death during I-M). 5Y PFS was 94% (95% CI 89%–100%) and 5Y OS was 99% (95% CI 96%–100%). There was no difference in PFS by IGHV status or duration of I-M (Figure A). Five pts progressed with CLL, all after cessation of IBR. Fourteen pts remained in response on continuous IBR therapy, two of whom had achieved BM-uMRD at 2Y but chose to continue IBR. We longitudinally tracked PB MRD of 69 pts treated with at least 2Y of I-M with available samples and observed high rates of PB-uMRD post-iFCR (75%) and after 2Y I-M (77%). At 4Y after completion of iFCR, 63% of evaluable pts maintained PB-uMRD (Figure B). Thirteen pts (15%) had MRD recurrence without clinical progression, mostly after stopping IBR; 62% of these pts had U-IGHV, 7% del17p, and 15% NOTCH1MUT. BTKMUT was not detected in any of the ten pts analyzed at time of MRD recurrence. One pt had PLCG2MUT at a low allele frequency (2%). Driver gene mutations were commonly detected at MRD recurrence (23% with TP53MUT, 38% with 1–2 other mutations per pt affecting NOTCH1, SF3B1, ATM, XPO1, and/or BRAF). Four of six pts (67%) who received IBR retreatment after MRD recurrence achieved PR. Median duration of IBR retreatment was 34 months. Serial PB MRD data from five pts on IBR retreatment revealed that the MRD growth stabilized but was not eradicated during retreatment. Keywords: chronic lymphocytic leukemia (CLL), minimal residual disease, molecular targeted therapies This study was funded by Pharmacyclics, an AbbVie Company. Conflicts of interests pertinent to the abstract I. E. Ahn Consultant or advisory role: BeiGene D. M. Brander Conflicts of interests pertinent to the abstract Consultant or advisory role: Pfizer, Pharmacyclics, Genentech, TG Therapeutics, ArQule/Merck, AbbVie Research funding: Juno/Celgene/BMS, AstraZeneca/Acerta, CATO/SMS Catapult, NeWave, DTRM, Genentech, BeiGene, MEI Pharma, ArQule/Merck, AbbVie Other remuneration: Ascentage J. Montegaard Consultant or advisory role: Pharmacyclics, Abbvie, AstraZeneca A. Alencar Consultant or advisory role: Amgen, Kite, Seagen, Epizyme, Janssen, BeiGene, Incyte, TG Therapeutics, Genentech, Lilly Research funding: Loxo, BeiGene, Incyte C. A. Jacobson Consultant or advisory role: Kite/Gilead, BMS/Celgene, Novartis, Miltenyi, Abintus Bio, Ipsen, Instil Bio, Daiichi-Sankyo, Morphosys, Caribou Bio, ImmPACT Bio, AztraZeneca Research funding: Kite/Gilead, Pfizer P. Armand Consultant or advisory role: Merck, BMS, Pfizer, Affimed, Adaptive, Infinity, ADC Therapeutics, Celgene, Morphosys, Daiichi Sankyo, Miltenyi, Tessa, GenMab, C4, Enterome, Regeneron, Epizyme, Astra Zeneca, Genentech, Xencor Honoraria: Merck, BMS Research funding: Kite; Research funding (institutional), Merck, BMS, Affimed, Adaptive, Tensha, Otsuka, Sigma Tau, Genentech/Roche, IGM J. Crombie Consultant or advisory role: Incyte, Karyopharm, Kite, ADC therapeutics, Genmab Research funding: Roche, Merck, Abbvie, Bayer A. S. LaCasce Consultant or advisory role: Seagen, Kite Honoraria: Research to practice J. Arnason Consultant or advisory role: BMS E. P. Hochberg Other remuneration: Leuko (Equity) J. S. Abramson Consultant or advisory role: Abbvie, Astra-Zeneca, BeiGene, Bluebird Bio, BMS, Celgene, Epizyme, Incyte, Kymera, Genmab, Genentech, Ono Pharma, Mustang Bio, MorphoSys, Regeneron, Century, Kite Pharma, Lilly, Janssen, Takeda, Caribou Biosciences, Interius, Cellectar J. R. Brown Consultant or advisory role: Abbvie, Acerta/Astra-Zeneca, BeiGene, Genentech/Roche, Grifols Worldwide Operations, Hutchmed, iOnctura, Janssen, Kite, Loxo/Lilly, MEI Pharma, Numab Therapeutics, Pfizer, Pharmacyclics Research funding: BeiGene, Gilead, iOnctura, Loxo/Lilly, MEI Pharma, TG Therapeutics M. S. Davids Consultant or advisory role: AbbVie, Adaptive Biosciences, Ascentage Pharma, AstraZeneca, BeiGene, BMS, Eli Lilly, Genentech, Janssen, Merck, Mingsight Pharmaceuticals, ONO Pharmaceuticals, Secura Bio, TG Therapeutics, Takeda Research funding: AbbVie, AstraZeneca, Ascentage Pharma, Genentech, MEI Pharma, Novartis, Surface Oncology, TG Therapeutics

PO-05-185 PREDICTION AND RISK OF ATRIAL FIBRILLATION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY: A DANISH NATIONWIDE COHORT STUDY

Hypertrophic cardiomyopathy (HCM) can be associated with serious complications such as heart failure, atrial fibrillation (AF) and sudden cardiac death. The treatment of AF in HCM patients can be challenging since AF often aggravates symptoms and increases the risk of stroke. Little is known on which factors contribute to the development of AF in these patients. To determine the incidence of AF in Danish HCM patients, identify risk factors for the development of AF and possible prediction tools for at-risk patients Through the Danish National Registers all patients without previous AF, aged 16 or older diagnosed with HCM between the 1st of January 2005, and the 31st of December 2018 were included in the analysis. The association between HCM and incident AF was investigated using multivariable Cox proportional-hazard analysis and odds ratios using linear regression. Cumulative incidence of AF was calculated using the Aalen-Johansen estimator, taking death as a competing risk into account. A total of 3,200 HCM patients without prevalent AF were included, median age was 66 years (IQR 55-77) and 48% were female. During the study period, 477 (15%) patients were diagnosed with incident AF. Risk of developing AF was increased for patients with obstructive HCM (HR 1.27 [95%CI 1.06 -1.53], p = 0.001) while there was no difference between genders. In patients classified as non-obstructive HCM, AF incidence likewise increased with rising CHADS-VASC score, however in the obstructive HCM category, AF incidence was high regardless of patients CHADS-VASC score. Further, for patients with non-obstructive HCM the odds ratio for incidental AF increased incrementally with rising CHADS-VASC score, while the CHADS-VASC score for patients with obstructive HCM followed no significant pattern. AF is a common complication in HCM. Patients with obstructive HCM were at increased risk of developing AF. The CHADS-VASC score is a potentially useful tool in identifying patients at risk for AF with non-obstructive HCM, however not in the presence of obstructive HCM.Tabled 1All patients and incident atrial fibrillationAll patientsWithout incident AFIncident AFNumber of patients32002723477Age: median in years (median [IQR])66 [54, 77]65 [53, 76]69 [59, 77]Gender: Female (%)1526 (48)1294 (47)232 (49)Age at or above 60 (%)2052 (64)1698 (62)354 (74)HCM type: obstructive (%)1477 (46)1211 (45)266 (56)Comorbidities:Hypertension (%)1490 (47)1216 (45)274 (57)Ischemic heart disease (%)640 (20)509 (19)131 (28)Heart failure (%)330 (10)276 (10)54 (11)Stroke (%)201 (6)174 (6)27 (6)Chronic obstructive pulmonary disease (%)231 (7)194 (7)37 (8)Chronic kidney disease (%)142 (4)126 (5)16 (3)CHADS - VASC ScoreCHADS - VASC = 0 (%)631 (20)575 (21)56 (12)CHADS - VASC = 1 (%)680 (21)591 (22)89 (19)CHADS - VASC = 2 (%)627 (20)515 (19)112 (23)CHADS - VASC = 3 (%)565 (18)470 (17)98 (20)CHADS - VASC = >3 (%)693 (21)571 (21)122 (26) Open table in a new tab

Relationship between postoperative atrial fibrillation and its recurrence after lung resection.

Atrial fibrillation (AF) frequently occurs after pulmonary resection and is commonly referred to as postoperative atrial fibrillation (POAF). This study explored whether or not POAF is related to the recurrence of AF in the chronic phase. A total of 1311 consecutive patients without a history of AF who underwent lung resection based on a diagnosis of lung tumor were retrospectively analyzed. POAF occurred in 46 patients (3.5%), and a logistic regression analysis revealed that the age (p < 0.05), history of hyperthyroidism (p < 0.05), and major lung resection (p < 0.05) were independent predictors of POAF. AF events in the chronic phase were observed in 15 (32.6%) and 45 (3.6%) patients with and without POAF, respectively. A Cox regression analysis revealed that POAF was the only independent predictor of AF development in the chronic phase (p < 0.01). The Kaplan-Meier curve and log-rank test revealed that the cumulative incidence of AF in the chronic phase was significantly higher in patients with POAF than in those without POAF (p < 0.01). POAF was an independent predictor for AF in the chronic phase after lung resection. Further investigations including cases of catheter ablation and optimal medical therapy for patients with POAF after lung resection are needed.

P552 Anti-TNF Treatment and Risk of Atrial Fibrillation in Inflammatory Bowel Disease Patients

Abstract Background Inflammation is thought to play a role in the development of atrial fibrillation (AF). Previous studies suggested that inflammatory bowel disease (IBD) is associated with increased risk of AF. These studies also found IBD patients receiving biologic agents were at higher risk of AF than patients not receiving them. We sought to determine the association between anti-TNF treatment and the risk of AF in IBD patients Methods In this observational cohort, we included all adult IBD patients who were registered in Rambam Medical Center, diagnosed with IBD from November 1983 to October 2021. We excluded patients who were diagnosed with AF and/or stroke prior to IBD diagnosis. Disease severity was based upon IBD treatment. Mild disease was defined as no treatment, 5-ASA, or topical steroids, while moderate-to-severe disease was defined as any immunomodulator, biologic or systemic steroid therapy. Primary outcome was AF diagnosis. We used Cox proportional hazard model to compare AF in patients receiving anti-TNF treatment to those with mild disease. We further adjusted the hazard ratio of AF development based on known AF risk factors, including age, male gender, cardiovascular disease, chronic kidney disease, pervious venous thromboembolism, hyperlipidemia, diabetes, and thyroid disease. Results Our initial cohort included 5,326 patients. After exclusion, 4,886 patients were included. Median follow-up time was 8.49 years 2,720 patients were considered as having mild IBD, while 787 patients received anti-TNF medications. During follow-up period, cumulative incidence of AF was 1.50% (n=41) and 0.89% (n=7), respectively (p=0.21). Unadjusted hazard ratio of AF occurrence in anti-TNF patients was 0.6 (95% CI; 0.27-1.3, p=0.211). After adjustment, hazard ratio of AF occurence was 1.33 (95% CI; 0.53-3.3, p=0.545). Conclusion Anti-TNF treatment was not associated with increased risk of AF among IBD patients. This provides reassurance regarding the cardiovascular safety of anti-TNFs in a real-world IBD cohort.

Atrial fibrillation and stroke risk of patients with hypertrophic cardiomyopathy in denmark from 2005-2018: a nationwide cohort study

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Internal funding: Herlev-Gentofte Cardiovascular Research Department. Background Hypertrophic cardiomyopathy (HCM) can be associated with serious complications such as heart failure, atrial fibrillation (AF) and sudden cardiac death. The treatment of AF in HCM patients can be challenging since AF often aggravates symptoms. Previous studies have suggested that HCM patients with AF have an elevated risk of thromboembolism and stroke compared to AF patients without HCM regardless of their CHA2DS2VASc score. Purpose To determine the risk of AF and stroke in HCM patients. Methods Through the Danish National Registers all patients aged 16 or older diagnosed with HCM between the 1st of January 2005, and the 31st of December 2018 were included in the analysis. The association between HCM, AF, and stroke was investigated using multivariable Cox proportional-hazard analysis adjusted for gender, age, atrial fibrillation, ischemic heart disease, chronic obstructive pulmonary disease, chronic kidney disease and hypertension. Cumulative incidence of AF and stroke was calculated using the Aalen-Johansen estimator, taking death as a competing risk into account. Results A total of 3856 patients were included, 2060 (53,4%) were male and median age of 67,8 (IQR 56 and 77,8) years. During the study period, 384 (10%) patients were diagnosed with AF. The risk of AF was significantly lower in males (HR 0,72 (0,59–0,90), p-value = 0.003) and for patients below 60 years (HR 0,18 (0,12–0,27), p-value = &amp;lt;0.001). (Figure 1) 157 (4,1%) of the HCM patients developed stroke. The risk of developing stroke was significantly decreased for patients aged under 60 (HR 0,32 (0,2–0,52), p-value = &amp;lt;0.001). There was no increased risk of stroke comparing genders. Stroke risk was further analyzed in patients with known AF at time of inclusion, 656 (17%) in total. Compared to patients without AF and adjusted for age, gender and co-morbidities, there was no significant difference in stroke risk between these groups (HR 1.2 (0,81-1,76), p-value = 0.36). (Figure 2) Conclusion AF and stroke are common complications in HCM. Women are more susceptible to developing AF than men, and age over 60 at the time of diagnosis was associated with significantly higher risk of AF and stroke. HCM patients with previously known AF did not have a significantly elevated risk of stroke. More research will be needed to further explore these connections.

Bidirectional Association Between Kidney Function and Atrial Fibrillation: A Population-Based Cohort Study.

BackgroundConsensus lacks concerning a bidirectional association between kidney function and atrial fibrillation (AF), but this is crucial information for prevention/treatment efforts for both chronic kidney disease and AF. Therefore, we investigated the bidirectional association between kidney function and AF.Methods and ResultsThis study was a prospective cohort study including 9228 participants (mean age, 64.9 years; 57.2% women) with information on kidney function (estimated glomerular filtration rate [eGFR] based on serum creatinine [eGFRcreat], cystatin C [eGFRcys], or both [eGFRcreat‐cys], and urine albumin‐to‐creatinine ratio) and AF. Reduced kidney function was defined as eGFRcreat <60 mL/min per 1.73 m2. Cox proportional‐hazards, logistic regression, linear mixed, and joint models were used to investigate the association of kidney function with AF and vice versa. During follow‐up (median of 8.0 years), 780 events of incident AF occurred. Lower eGFRcys and eGFRcreat‐cys were associated with increased AF risk (hazard ratio [HR], 1.08 [95% CI, 1.03–1.14] and HR, 1.07 [95% CI, 1.01–1.14], respectively, per 10 mL/min per 1.73 m2 eGFR decrease). For eGFRcys and eGFRcreat‐cys, 10‐year cumulative incidence of AF was 16% (eGFR <60) and 6% (eGFR ≥60). Prevalent AF (versus no prevalent AF) was associated with 2.85 mL/min per 1.73 m2 lower eGFRcreat and with a faster decline of eGFRcreat with age. Prevalent AF was associated with a 1.3‐fold increased risk of incident reduced kidney function.ConclusionsKidney function, especially eGFRcys, and AF are bidirectionally associated. There are currently no targeted prevention efforts for AF in patients with mild chronic kidney disease and vice versa. Our results could provide the first step to improve prediction/prevention of both conditions.

Effect of Alirocumab on Incidence of Atrial Fibrillation After Acute Coronary Syndromes: Insights from the ODYSSEY OUTCOMES Trial

BackgroundUsing data from the ODYSSEY OUTCOMES trial (NCT01663402), we sought to identify factors associated with the development of incident atrial fibrillation in patients with recent acute coronary syndrome without prior atrial fibrillation and to determine whether alirocumab treatment influenced risk of incident atrial fibrillation. MethodsODYSSEY OUTCOMES compared alirocumab treatment with placebo in 18,924 patients with recent acute coronary syndrome and dyslipidemia despite high-intensity or maximum-tolerated statin therapy. The primary outcome of major adverse cardiovascular events (MACE) comprised death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischemic stroke, or unstable angina requiring hospitalization. Patients were classified as having previous atrial fibrillation (present prior to or at randomization) or no previous atrial fibrillation. A multivariable model was used to determine factors associated with incident atrial fibrillation. ResultsAmong 18,262 participants without prior atrial fibrillation at baseline, 499 (2.7%) had incident atrial fibrillation during follow-up. Older age, history of heart failure or myocardial infarction, and higher body mass index were significantly associated with incident atrial fibrillation. Treatment with alirocumab or placebo did not influence the cumulative incidence of atrial fibrillation (hazard ratio 0.91; 95% confidence interval, 0.77-1.09). Patients with vs without a history of atrial fibrillation had a higher incidence of MACE (8.8 vs 3.7 events per 100 patient-years), without significant interaction between atrial fibrillation and randomized treatment on risk of MACE (Pinteraction = .78). ConclusionsWhile alirocumab did not modify risk of incident atrial fibrillation after acute coronary syndrome, it did reduce the risk of MACE, regardless of prior atrial fibrillation history. History of atrial fibrillation is an independent predictor of recurrent cardiovascular events after acute coronary syndrome.

Cardiovascular Diseases Following Breast Cancer: Towards a Case-by-Case Assessment Through a Prediction Risk Score Model in 943 Patients.

To identify patients at high risk of developing cardiovascular disease through the identification of risk factors among a large population of breast cancer women and to assess the performance of Abdel-Qadir risk prediction model score. The medical records and baseline characteristics of all patients/tumors diagnosed with breast cancer from 2010 to 2011 in a French comprehensive cancer center were collected. Cardiovascular events were defined as arterial and cardiac events, atrial fibrillation and venous thromboembolism occurring during the 5-year follow-up. Abdel-Qadir multivariable prediction model for major adverse cardiovascular events were used with the concordance index (c-index) score to assess calibration by comparing predicted risks to observed probabilities. Among the 943 breast cancer patients included, 83 patients (8.8%) presented with at least one cardiovascular event, leading to a cumulative incidence of 0.07 at 5 years (95% confidence interval [CI], 0.055-0.088). The cumulative incidence of atrial fibrillation at 5 years was 0.01 (95% CI, 0.005-0.018). Factors associated with the occurrence of cardiovascular events were pre-existing cardiovascular diseases including high blood pressure (hazard ratio [HR]=1.78, 95% CI=1.07-2.97, P=0.028), acute coronary syndrome (HR=5.28, 95% CI: 2.16-12.88, P<0.05) and grade 3 Scarff-Blool-Richardson (HR=1.95, 95% CI: 1.21-3.15, P=0.006). With a c-index inferior to 0.7, the Abdel-Qadir score was not fully validated in our population. These findings call for the assessment of the performance of risk prediction models such as Abdel-Qadir score coupled with other factors such as Scarff Bloom and Richardson grading in order to identify patients at high risk of experiencing cardiotoxicity.

The association of education and household income with the lifetime risk of incident atrial fibrillation: The Framingham Heart study

BackgroundSocial determinants of health, in particular education and income, influence the incidence, management, and outcomes of cardiovascular diseases including atrial fibrillation (AF). Data are limited on the associations of socioeconomic status with lifetime risk of incident AF. MethodsWe selected 2172 FHS participants (51% women) who were free of AF at the index age of 55 years. We assessed educational attainment (≥college) at the last exam prior to index age and household income ($40k/50k/≥55k depending on the FHS cohort). We estimated the lifetime risk of AF as the cumulative incidence of AF, accounting for the competing risk of death, at age 95 years. We analyzed strata defined by education and household income separately, and by combining education and household income. We adjusted analyses for sex, height, weight, systolic and diastolic blood pressure, current smoking, alcohol consumption, use of antihypertensive medication, diabetes, history of myocardial infarction, and history of heart failure. ResultsOver a mean follow-up of 13 years, 265 participants developed incident AF. The lifetime risk of developing AF was 32.5% (95%CI, 26.5% to 38.5%) and 32.5% (95%CI, 28.7% to 38.3%) among participants with lower and higher education attainment (p=0.98). The lifetime risk of developing AF was 32.1% (95%CI, 26.7% to 37.5%) and 31.8% (95%CI, 26.6% to 36.9%) among participants with lower and higher household income (p=0.79). There was no evidence of interaction between education and income on lifetime risk of AF (p = 0.84). Results were similar in subgroups of women and men. ConclusionIn our community-based sample, there was no evidence of an association between education or household income and lifetime risk of AF.

Abstract 13980: The Association of Education and Household Income With the Lifetime Risk of Incident Atrial Fibrillation: The Framingham Heart Study

Introduction: Social determinants of health, in particular education and income, influence the incidence, management, and outcomes of cardiovascular diseases including atrial fibrillation (AF). However, data are limited on the effect of socioeconomic status on the lifetime risk of incident AF. We assessed the association of income and education with lifetime risk of AF in the Framingham Heart Study (FHS). Methods: We selected 2172 FHS participants (51% women) who were free of AF at the index age of 55 years. We assessed educational attainment (some college or more) at the last exam prior to index age and household income ($40k/50k/55k or more depending on the FHS cohort). We estimated the lifetime risk of AF as the cumulative incidence of AF, accounting for the competing risk of death, at age 95 years. We analyzed strata defined by education and household income separately, and by combining education and household income. We adjusted analyses on sex, height, weight, systolic and diastolic blood pressure, current smoking, use of antihypertensive medication, diabetes, history of myocardial infarction, and history of heart failure. Results: Over a mean follow-up of 13 years, 265 participants developed incident AF. The lifetime risk of developing AF was 32.5% (95%CI, 26.5% to 38.5%) and 32.5% (95%CI, 28.7% to 38.3%) among participants with lower and higher education attainment (p=0.98). The lifetime risk of developing AF was 32.1% (95%CI, 26.7% to 37.5%) and 31.8% (95%CI, 26.6% to 36.9%) among participants with lower and higher household income (p=0.79). There was no evidence of an interaction between education and income on lifetime risk of AF (p = 0.84). Results were similar in subgroups of women and men. Conclusions: In our community-based sample, there was no evidence of association between education or household income and lifetime risk of AF

Safety and Medium- and Long-Term Efficacy of Treating Atrial Fibrillation with Surgical Radiofrequency Ablation during Concomitant Mitral Valve Surgery

To investigate the safety and medium- and long-term efficacy of surgical radiofrequency ablation to treat atrial fibrillation during concomitant mitral valve surgery. From January 2014 to December 2018, 280 patients with mitral valve disease and the comorbidity of preoperative atrial fibrillation were recruited for the study. Among them, 130 patients received only mitral valve surgery (non-ablation group), and 150 patients were underwent surgical radiofrequency ablation for the atrial fibrillation during concomitant mitral valve surgery (ablation group). Among the 150 patients of the ablation group, 80 had biatrial ablation, and 70 had left atrial ablation. Under general anesthesia, median sternotomy was done on all patients and cardiopulmonary bypass was established through the ascending aorta and superior and inferior venae cavae. After aortic occlusion, patients in the ablation group underwent the ablation procedure with the Atricure® bipolar ablation device, using the Cox Maze Ⅲ procedure as a reference. In addition, the left atrial appendage was removed and electrocautery of the ligament of Marshall and Waterston's groove were performed in all Cox Maze cases. Following ablation, mitral valve replacement or repair was performed. All patients were given 200 mg oral amiodarone on the first day after surgery, for three times/d×7 d, which was followed by twice/d×7 d, and then oral amiodarone 200 mg/d was maintained till the end of 3 months after surgery (ablation group) or 12 months after surgery (non-ablation group). Patients were followed up at the intervals of 3 months, 6 months, 12 months, 2 years, 3 years, and 5 years after discharge. The follow-up service included standard 12-lead chest electrocardiogram (ECG) and 24-h dynamic ECG. The primary end point of the study was the time point of postoperative atrial fibrillation and the secondary endpoints were major cardiovascular events, death, and readmission due to heart failure. The surgeries were successfully performed in all subjects of the study. A total of 30 patients were lost to follow-up within 5 years after operation (10.7% losses to follow-up), including 11 patients in the ablation group and 19 patients in the non-ablation group. The proportion of patients who did not have atrial fibrillation in the ablation group and the non-ablation group at 6 months, 12 months, 2 years, 3 years and 5 years after surgery was 83.3% and 27.7%, 72.7% and 20.8%, 66.0% and 15.4% 61.3% and 13.1%, and 43.3% and 10.8%, respectively, with the data from the two groups showing statistically significant difference ( P<0.001). The proportion of patients who did not have atrial fibrillation in the biatrial ablation and the left atrial ablation group at 6 months, 12 months, 2 years, 3 years and 5 years after surgery was 87.3% and 87.5%, 92.4% and 82.8%, 90.5% and 85.7%, 94.8% and 88.1%, and 75.5% and 69.4%%, respectively, with the data from the two groups showing no statistically significant difference ( P>0.05). However, the cumulative incidence of atrial fibrillation in the two groups showed statistically significant difference ( P<0.001). There were no deaths within 30 days after operation in either group. There was no significant difference in cerebrovascular accident, readmission for heart failure, pulmonary infection and mediastinal infection between the two groups within one year after operation ( P>0.05). However, the proportion of patients who had permanent pacemaker installed due to Ⅲ-degree atrioventricular block in the ablation group was higher than that in the non-ablation group ( P<0.05). The proportion of patients who required re-drainage due to delayed pericardial effusion in the ablation group was higher than that in the non-ablation group ( P<0.05). In the group of patients who had modified Cox Maze procedure with bipolar ablation device to treat atrial fibrillation during concomitant mitral valve surgery, the maintenance rate of sinus rhythm after cardioversion was significantly higher than that in the non-ablation group. The surgery showed better safety and significantly better medium- and long-term outcomes. Left atrial ablation and biatrial ablation were both considered safe and effective surgical treatment for atrial fibrillation. Compared with the left atrial ablation group, the biatrial ablation group achieved better effects in restoring and maintaining sinus rhythm without an increase the incidence of perioperative complications.

Abstract P004: Association Between The Liver Fibrosis-4 Score And Incident Atrial Fibrillation In A General Japanese Population Of Middle-aged To Older Adults

Background: There is increasing evidence that end-organ liver dysfunction is an important risk factor for atrial fibrillation (AF). Whether a non-invasive, laboratory-based marker of liver fibrosis, the fibrosis-4 score (FIB-4), is associated with incident AF is not known. Aim: To examine the longitudinal association of FIB-4 with incident AF in a general Japanese population with public health insurance. Methods: We used data from the National Japanese Health Check-Up performed in Kanazawa City, which included unemployed or retired participants aged ≥ 40 years. The baseline examination occurred in 2013 and participants were invited for annual routine examinations with follow-up data available through 2018. We excluded participants with pre-existing AF or missing data at baseline or follow-up. Incident AF was based on 12-lead electrocardiogram. We calculated the FIB-4 score (composed of age [years], aspartate and alanine aminotransferase, and platelet levels) for each participant and estimated the cumulative incidence of AF stratified by FIB-4 score quartiles. We also examined the association between quartiles of FIB-4 and incident AF using Cox proportional hazard models adjusted for risk factors with the lowest FIB-4 quartile as referent. Results: Of 37,892 participants, 37% were male and mean age was 72.4±9.6 years. Median (interquartile range [IQR]) of the FIB-4 score was 1.75 (IQR 1.38, 2.27). During a median (IQR) follow-up period of 5.0 years (4.0, 5.0), 707 cases of incident AF were identified. Cumulative incidence in the highest quartile of FIB-4 was 3.9% compared with 1.0% in the lowest quartile (log-rank p&lt;0.001, Figure A ). Higher quartiles of the FIB-4 score had a dose-dependent increased risk of AF with adjusted HR of 1.70 (1.29, 2.23) in the highest quartile compared with the lowest quartile ( Figure B ). Conclusion: FIB-4 was independently associated with incident AF in a general, older Japanese population and may reflect risk of AF, in addition to traditional cardiovascular risk factors.

Abstract P708: Artificial Intelligence Enabled-Electrocardiography for the Detection of Cerebral Infarcts in Patients With Atrial Fibrillation

Background: Atrial fibrillation (AF) is an established risk factor for ischemic stroke, but it can be paroxysmal and may go undiagnosed. An artificial intelligence (AI)-enabled ECG acquired during normal sinus rhythm was recently shown to detect silent AF. The objective of this study was to determine if AI-ECG AF score is associated with presence of cerebral infarcts. Methods: Participants from a population-based study ages 30 to 95 years with T2 fluid attenuation inversion recovery (FLAIR) MRI obtained between October 10, 2011, and November 2, 2017 were considered for inclusion. Participants without ECG were excluded. AI-ECG score was calculated using most recent ECG with normal sinus rhythm at the time of MRI. Presence of infarcts was determined on FLAIR MRI scans. Logistic regression was run to evaluate the relationship between AI-ECG AF score and presence of cerebral infarcts. Similar analyses were performed using history of AF rather than AI-ECG AF score as predictor. Age and sex were included as covariates. We also examined whether a high-threshold AI-ECG score was associated with infarcts. In a prior study, an AI-ECG AF score &gt; 0.5 was associated with a cumulative incidence of AF of 21.5% at 2 years and 52.2% at 10 years. Results: This study included 1,373 individuals. Average age was 69.6 years and 53% of participants were male. There were 136 (10%) individuals with ECG-confirmed AF; 1237 (90%) participants had no AF history. Of participants with AF, 23% (n=31) were on anticoagulation, 47% (n=64) were on antiplatelet and 18% (n=24) were on dual therapy. Only 1.3% (n=16) of patients without AF were on anticoagulation and 47% (n=578) were on antiplatelet therapy. Ischemic infarcts were detected in 214 (15.6%) patients. As a continuous measure AI-ECG was associated with infarcts but not after adjusting for age and sex (p=0.46). AI-ECG AF score &gt; 0.5 was associated with infarcts ( p &lt; 0.001); even after adjusting for age and sex ( p = 0.03). History of AF was also associated with infarcts after adjusting for age and sex ( p = 0.018). Conclusion: AI-ECG AF score and history of AF were associated with presence of cerebral infarcts after adjusting for age and sex. This tool could be useful in select patients with cryptogenic stroke but further investigation would be required.

Artificial Intelligence-Electrocardiography to Predict Incident Atrial Fibrillation: A Population-Based Study.

An artificial intelligence (AI) algorithm applied to electrocardiography during sinus rhythm has recently been shown to detect concurrent episodic atrial fibrillation (AF). We sought to characterize the value of AI-enabled electrocardiography (AI-ECG) as a predictor of future AF and assess its performance compared with the CHARGE-AF score (Cohorts for Aging and Research in Genomic Epidemiology-AF) in a population-based sample. We calculated the probability of AF using AI-ECG, among participants in the population-based Mayo Clinic Study of Aging who had no history of AF at the time of the baseline study visit. Cox proportional hazards models were fit to assess the independent prognostic value and interaction between AI-ECG AF model output and CHARGE-AF score. C statistics were calculated for AI-ECG AF model output, CHARGE-AF score, and combined AI-ECG and CHARGE-AF score. A total of 1936 participants with median age 75.8 (interquartile range, 70.4-81.8) years and median CHARGE-AF score 14.0 (IQR, 13.2-14.7) were included in the analysis. Participants with AI-ECG AF model output of >0.5 at the baseline visit had cumulative incidence of AF 21.5% at 2 years and 52.2% at 10 years. When included in the same model, both AI-ECG AF model output (hazard ratio, 1.76 per SD after logit transformation [95% CI, 1.51-2.04]) and CHARGE-AF score (hazard ratio, 1.90 per SD [95% CI, 1.58-2.28]) independently predicted future AF without significant interaction (P=0.54). C statistics were 0.69 (95% CI, 0.66-0.72) for AI-ECG AF model output, 0.69 (95% CI, 0.66-0.71) for CHARGE-AF, and 0.72 (95% CI, 0.69-0.75) for combined AI-ECG and CHARGE-AF score. In the present study, both the AI-ECG AF model output and CHARGE-AF score independently predicted incident AF. The AI-ECG may offer a means to assess risk with a single test and without requiring manual or automated clinical data abstraction.

Abstract 15005: Associations Between Alcohol Intake and Genetic Predisposition With Atrial Fibrillation Risk in a National Biobank

Introduction: Excess alcohol intake and inherited predisposition may increase risk of atrial fibrillation (AF). We sought to characterize the association between alcohol intake and incident AF and determine whether the effect of alcohol is modified by inherited predisposition to AF. Methods: We analyzed UK Biobank participants without prevalent AF and with complete alcohol consumption, genomic, and clinical data collected between 2006-2010. Exposures included alcohol consumption (stratified by an acceptable range of ≤98 grams/week for women or ≤196 grams/week for men and analyzed as a continuous variable) and an AF polygenic risk score (PRS). Cox proportional hazard models were adjusted for established AF risk factors. The cumulative incidence of AF was assessed at 5 years. Results: Among 376,776 participants (47.5% male, mean age 56.9 years), 6,293 developed AF during a median of 6.9 years of follow-up. Alcohol consumption was associated with AF (hazard ratio [HR] 1.10; 95% CI 1.05-1.16 for intake above an acceptable range; HR 1.04 per 100 grams/week; 95% CI 1.02-1.06). An AF PRS was associated with AF (HR 1.38 per standard deviation [SD]; 95% CI 1.35-1.41). In models including both alcohol intake and the AF PRS, each remained associated with AF. The 5-year cumulative incidence of AF for individuals with alcohol intake above an acceptable range and in the highest decile of polygenic risk was 2.33% (95% CI 2.07-2.59), compared to 0.69% (95% CI 0.58-0.80) for those with alcohol intake within acceptable range and in the lowest decile of polygenic risk. Conclusions: Alcohol consumption is associated with risk of incident AF across a range of polygenic predisposition to AF. Preventive counseling regarding alcohol intake may reduce the risk of AF regardless of the degree of risk conferred by inherited predisposition.

Abstract 13015: First-degree Atrioventricular Block is Associated With Incident Atrial Fibrillation in the Japanese General Population Aged ≥ 40 Years

Introduction: First-degree atrioventricular block (fAVB) is a common cardiac conduction disorder diagnosed by prolongation of the PR interval ≥220 msec. Although it is generally considered benign, some previous studies demonstrated that fAVB was associated with incident atrial fibrillation (AF). However, evidence is scarce regarding the association between fAVB and incident AF in older populations. Hypothesis: We hypothesized that fAVB was significantly associated with incident AF in older populations. Methods: Eligible participants were residents in Kanazawa City who aged ≥ 40 years and underwent 12-lead ECG at the national Japanese health checkups in 2013. Participants with AF detected at the baseline exam and with no follow-up examinations between 2014 and 2018. fAVB was defined as PR interval ≥ 220 msec based on the Minnesota code (6-3). Incident AF was defined as the first episode of AF detected by 12-lead ECG at the annual health checkups. The cumulative incidence of AF was estimated by the Kaplan Meier curve analysis, and statistical significance was evaluated by the log-rank test. Unadjusted and adjusted hazard ratios (HRs) were computed by the Cox proportional hazard model. HRs were adjusted using three models in which conventional risk factors for AF were included (Table). Results: 37,730 participants (mean age, 72.3 ± 9.6 years; Male, 37%) were included. Baseline fAVB was observed in 667 (1.8%) participants. During the median follow-up period of 5 years (interquartile range, 4.0 - 5.0 years), 691 cases of incident AF were observed. Kaplan Meier curve showed that a 5-year cumulative incidence of AF was significantly higher in fAVB (+) group compared with fAVB (-) group (6.8% vs 2.1%, p &lt; 0.01). In the fully adjusted model, fAVB was significantly associated with incident AF (HR, 1.75; 95% confidence interval, 1.25 - 2.45; p-value &lt; 0.01) (Table). Conclusion: fAVB was independently associated with incident AF in this predominantly elderly Japanese population.