Abstract 15303: The Impact of Heart Rate on the Incidence of Cardiovascular Events in Patients With Chronic Atrial Fibrillation: The Fushimi Af Registry

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Moritake Iguchi ◽  
Hisashi Ogawa ◽  
Hirofumi Sugiyama ◽  
Nobutoyo Masunaga ◽  
Mitsuru Ishii ◽  
...  

Purpose: Previous reports suggested that lenient rate control was not inferior to strict rate control among patients with chronic atrial fibrillation (AF). However, the impact of heart rate (HR) on the incidence of cardiovascular events is not clearly understood. Methods: The Fushimi AF Registry, a community-based prospective survey, was designed to enroll all of the AF patients in Fushimi-ku, Kyoto, Japan. At present, follow-up data were available in 3,514 patients (median follow-up period, 842 days). 1,622 patients had chronic AF, and we obtained ECG findings in 1,561 patients. We divided these patients into three groups based on their heart rate; high-HR (HR≥110) (n=179), intermediate-HR (80≤HR<110) (n=695), and low-HR (HR<80) (n=687), and explored the cardiovascular events (composite of cardiovascular death, hospitalization for heart failure, and arrhythmic events). Results: Mean HR was 128±13 bpm, 93±8 bpm, and 67±9 bpm, respectively. High HR group was younger than other groups, but the prevalence of heart failure was the highest (44.7%, 37.0%, 32.3%; p=0.007) and left-ventricular ejection fraction was the lowest (56.5±14.6%, 60.7±11.9%, 62.7±10.5%; p<0.0001). Prescription of beta-blocker (37.4%, 28.9%, 30.0%) and diltiazem (2.8%, 2.9%, 4.2%) was comparable, but prescription of verapamil was the highest in high-HR group (19.0%, 12.4%, 8.0%; p=0.0001), and prescription of digitalis was the highest in low-HR group (14.0%, 18.2%, 23.4%; p=0.005). Mean CHADS2 score was 2.3±1.3, 2.2±1.3, and 2.2±1.4, respectively. In Kaplan-Meier analysis, the incidence of cardiovascular events was higher in high-HR groups than intermediate- and low-HR group (9.2%/year vs 5.8%/year, p=0.02), but was similar between intermediate- and low-HR group (6.2%/year vs 5.4%/year, p=0.3). The incidence of stroke or systemic embolism was comparable between the three groups (2.6%/year, 3.6%/year, 2.4%/year). Cox proportional hazard ratios [95%CI] of high- and intermediate-HR for cardiovascular events compared to low-HR were 1.63 [1.06-2.44] and 1.10 [0.81-1.79], respectively. Conclusions: Among chronic AF patients, the incidence of cardiovascular events was higher in the patients with high-HR, but was similar between intermediate- and low-HR groups.

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Ikeda ◽  
M Iguchi ◽  
H Ogawa ◽  
Y Aono ◽  
K Doi ◽  
...  

Abstract Background Hypertension is one of the major risk factors of cardiovascular events in patients with atrial fibrillation (AF). However, relationship between diastolic blood pressure (DBP) and cardiovascular events in AF patients remains unclear. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in Japan. Follow-up data were available in 4,466 patients, and 4,429 patients with available data of DBP were examined. We divided the patients into three groups; G1 (DBP&lt;70 mmHg, n=1,946), G2 (70≤DBP&lt;80, n=1,321) and G3 (80≤DBP, n=1,162), and compared the clinical background and outcomes between groups. Results The proportion of female was grater in G1 group, and the patients in G1 group were older and had higher prevalence of heart failure (HF), diabetes mellitus (DM), chronic kidney disease (CKD). Prescription of beta blockers was higher in G1 group, but that of renin-angiotensin system-inhibitors and calcium channel blocker was comparable. During the median follow-up of 1,589 days, in Kaplan-Meier analysis, the incidence rates of cardiovascular events (composite of cardiac death, ischemic stroke and systemic embolism, major bleeding and HF hospitalization during follow up) were higher in G1 group and G3 group than G2 group (Figure 1). When we divided the patients based on the systolic blood pressure (SBP) at baseline (≥130 mmHg or &lt;130 mmHg), the incidence of rates of cardiovascular events were comparable among groups. Multivariate Cox proportional hazards regression analysis including female gender, age (≥75 years), higher SBP (≥130 mmHg), DM, pre-existing HF, CKD, low left ventricular ejection fraction (&lt;40%) and DBP (G1, G2, G3) revealed that DBP was an independent determinant of cardiovascular events (G1 group vs. G2 group; hazard ratio (HR): 1.40, 95% confidence intervals (CI): 1.19–1.64, G3 group vs. G2 group; HR: 1.23, 95% CI: 1.01–1.49). When we examined the impact of DBP according to 10 mmHg increment, patients with very low DBP (&lt;60 mmHg) (HR: 1.50,95% CI:1.24–1.80) and very high DBP (≥90 mmHg) (HR: 1.51,95% CI:1.15–1.98) had higher incidence of cardiovascular events than patients with DBP of 70–79 mmHg (Figure 2). However, when we examined the impact of SBP according to 20 mmHg increment, SBP at baseline was not associated with the incidence of cardiovascular events (Figure 3). Conclusion In Japanese patients with AF, DBP exhibited J curve association with higher incidence of cardiovascular events. Funding Acknowledgement Type of funding source: None


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Fujimoto ◽  
N Doi ◽  
K Hirai ◽  
M Naito ◽  
S Shizuta ◽  
...  

Abstract Introduction The presence of atrial fibrillation (AF) in patients with reduced left ventricular ejection fraction (LVEF) is associated with increased risks of mortality and hospitalization for heart failure (HF). Although prior studies reported that catheter ablation (CA) for AF in low LVEF patients reduced risks of all-cause mortality and HF hospitalization, the predictors of worsening HF after ablation has not been adequately evaluated. Purpose The purpose of this study was to investigate the impact of improvement in LVEF after AF ablation on the incidence of subsequent HF hospitalization in patients with low LVEF. Methods The Kansai Plus Atrial Fibrillation (KPAF) Registry is a multicenter registry enrolling 5,013 consecutive patients undergoing first-time ablation for AF. The current study population consisted of 1,031 patients with reduced LVEF of <60%. We divided the study population into 3 groups according to LVEF at follow-up; 678 patients (65.8%) with improved LVEF (≥5 U change in LVEF), 288 patients (27.9%) with unchanged LVEF (−5 U ≤ change in LVEF <5 U) and 65 patients (6.3%) with worsened LVEF (<−5 U change in LVEF). Results During the median follow-up of 1067 [879–1226] days, patients improved LVEF had lower rate of HF hospitalization, compared with those with unchanged and worsened LVEF (2.1%, 8.0%, and 21.5%, respectively, P<0.0001). Recurrent atrial tachyarrhythmias were documented in 43.5%, 47.2% and 67.7%, respectively (P=0.0008). Figure 1 Conclusion Among patients with reduced LVEF undergoing AF ablation, patients with subsequently improved LVEF in association with maintained sinus rhythm had markedly lower risk of HF hospitalization during follow-up as compared with those with unchanged or worsened LVEF.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Antonio Leon-Justel ◽  
Jose I. Morgado Garcia-Polavieja ◽  
Ana Isabel Alvarez-Rios ◽  
Francisco Jose Caro Fernandez ◽  
Pedro Agustin Pajaro Merino ◽  
...  

Abstract Background Heart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF with a reduced left ventricular ejection fraction (HFrEF). Methods This is a before and after interventional study, that assesses the impact of a personalized follow-up procedure for HF on patient’s outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before the intervention and again after the intervention. The primary objective was the rate of readmissions, due to a HF. Secondary outcome compared the rate of ED visits and quality of life improvement assessed by the number of patients who had reduced NYHA score. A cost-analysis was also performed on these data. Results Admission rates significantly decreased by 19.8% after the intervention (from 30.2 to 10.4), the total hospital admissions were reduced by 32 (from 78 to 46) and the total length of stay was reduced by 7 days (from 15 to 9 days). The rate of ED visits was reduced by 44% (from 64 to 20). Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was € 72,769 per patient (from € 201,189 to € 128,420) and €139,717.65 for the whole group over 1 year. Conclusions A personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care-associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.


2021 ◽  
Vol 10 (21) ◽  
pp. 4989
Author(s):  
Mohammad Abumayyaleh ◽  
Christina Pilsinger ◽  
Ibrahim El-Battrawy ◽  
Marvin Kummer ◽  
Jürgen Kuschyk ◽  
...  

Background: The angiotensin receptor-neprilysin inhibitor (ARNI) decreases cardiovascular mortality in patients with chronic heart failure with a reduced ejection fraction (HFrEF). Data regarding the impact of ARNI on the outcome in HFrEF patients according to heart failure etiology are limited. Methods and results: One hundred twenty-one consecutive patients with HFrEF from the years 2016 to 2017 were included at the Medical Centre Mannheim Heidelberg University and treated with ARNI according to the current guidelines. Left ventricular ejection fraction (LVEF) was numerically improved during the treatment with ARNI in both patient groups, that with ischemic cardiomyopathy (n = 61) (ICMP), and that with non-ischemic cardiomyopathy (n = 60) (NICMP); p = 0.25. Consistent with this data, the NT-proBNP decreased in both groups, more commonly in the NICMP patient group. In addition, the glomerular filtration rate (GFR) and creatinine changed before and after the treatment with ARNI in both groups. In a one-year follow-up, the rate of ventricular tachyarrhythmias (ventricular tachycardia and ventricular fibrillation) tended to be higher in the ICMP group compared with the NICMP group (ICMP 38.71% vs. NICMP 17.24%; p = 0.07). The rate of one-year all-cause mortality was similar in both groups (ICMP 6.5% vs. NICMP 6.6%; log-rank = 0.9947). Conclusions: This study shows that, although the treatment with ARNI improves the LVEF in ICMP and NICMP patients, the risk of ventricular tachyarrhythmias remains higher in ICMP patients in comparison with NICMP patients. Renal function is improved in the NICMP group after the treatment. Long-term mortality is similar over a one-year follow-up.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Polovina ◽  
I Milinkovic ◽  
G Krljanac ◽  
I Veljic ◽  
I Petrovic-Djordjevic ◽  
...  

Abstract Background Type 2 diabetes (T2DM) portends adverse prognosis in patients with atrial fibrillation (AF). Whether T2DM independently increases the risk of incident heart failure (HF) in AF is uncertain. Also, HF phenotype developing in patients with vs. those without T2DM has not been characterised. Purpose In AF patients without a history of prior HF, we aimed to assess: 1) the impact of T2DM on the risk of new-onset HF; and 2) the association between T2DM and HF phenotype developing during the prospective follow-up. Methods We included diabetic and non-diabetic AF patients, without a history of HF. Baseline T2DM status was inferred from medical history, haemoglobin A1c levels and oral glucose tolerance test. Study outcome was the first hospital admission or emergency department treatment for new-onset HF during the prospective follow-up. The phenotype of new-onset HF was determined by echocardiographic exam performed following clinical stabilisation (at hospital discharge, or within a month after HF diagnosis). HF phenotype was defined as HFrEF (left ventricular ejection fraction [LVEF] <40%), HFmrEF (LVEF 40–49%) or HFpEF (LVEF≥50%). Cox regression analyses adjusted for age, sex, baseline LVEF, comorbidities, smoking status, alcohol intake, AF type (paroxysmal vs. non-paroxysmal) and T2DM treatment was used to analyse the association between T2DM and incident HF. Results Among 1,288 AF patients without prior HF (mean age: 62.1±12.7 years; 61% male), T2DM was present in 16.5%. Diabetic patients had higher mean baseline LVEF compared with nondiabetic patients (50.0±6.2% vs. 57.6±9.0%; P<0.001). During the median 5.5-year follow-up, new-onset HF occurred in 12.4% of patients (incidence rate, 2.9; 95% confidence interval [CI], 2.5–3.3 per 100 patient-years). Compared with non-diabetic patients, those with T2DM had a hazard ratio of 2.1 (95% CI, 1.6–2.8; P<0.001) for new-onset HF, independent of baseline LVEF or other factors. In addition, diabetic patients had a significantly greater decline in covariate-adjusted mean LVEF (−10.4%; 95% CI, −9.8% to −10.8%) at follow-up, compared with nondiabetic patients (−4.0%; 95% CI, −3.8% to −4.2%), P<0.001. The distribution of HF phenotypes at follow-up is presented in Figure. Among patients with T2DM, HFrEF (56.9%) was the most common phenotype of HF, whereas in patients without T2DM, HF mostly took the phenotype of HFpEF (75.0%). Conclusions T2DM is associated with an independent risk of new-onset HF in patients with AF and confers a greater decline in LVEF compared to individuals without T2DM. HFrEF was the most prevalent presenting phenotype of HF in AF patients with T2DM.


EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
S Seliutskii ◽  
N Savina ◽  
A Chapurnykh

Abstract Objective to compare the efficacy of radiofrequency ablation (RFA) and drug therapy in patients with atrial fibrillation (AFib) and heart failure (HF) within 12-month follow-up. Materials and methods 130 patients (men-75%, average age-62.8 ± 11.8 years) with AFib and HF with left ventricular ejection fraction (LVEF)&lt;50% were included in a prospective study. In 107 (82%) of the included patients, intermediate LVEF was detected (40-49%). At the time of inclusion, paroxysmal AFib (PaAFib) was recorded in 60 (46%) of patients and persistent AFib (PeAFib) in 70 (54%). AFib RFA was performed in 65 patients, 65 patients continued to receive optimal antiarrhythmic therapy. Prior to the intervention and after 12 months, all patients underwent transthoracic echocardiography and quality of life (QoL) assessment using the SF-36 questionnaire. Results the freedom from AFib within 12 months follow-up period was registred in 49 (75%) of patients in the RFA group and 26 (40%) in the drug therapy group. After 12 month follow-up period we revealed increase of LVEF (p &lt; 0.001), decrease of anteroposterior size (p &lt;0.001) and volume (p &lt; 0.001) of left atrium (LA), improvement of mental (p = 0.008) and physical (p = 0.048) health components according to the SF-36 questionnaire in the RFA group. In the group of drug rhythm control, after 12 months there was only the improvement of mental (p = 0.006) and physical p = 0.016) health components and it was much less than in RFA group (р&lt;0.001). Similar results were received in patients who were free from Afib within 12 months in both groups. Conclusions in patients with AFib and HF with LVEF &lt; 50%, restoration and maintenance of sinus rhythm using RFA was accompanied by an increase in LVEF, decrease of  LA size, and an improvement of QoL. In the group of drug therapy, there was a lower freedom from AFib and there was the slight improvement only in QoL.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Brito ◽  
J.R Agostinho ◽  
C Duarte ◽  
B Silva ◽  
S Pereira ◽  
...  

Abstract Introduction Metabolic control plays an important role on major cardiovascular events (MACE) prevention. The 2019 ESC guidelines on dyslipidaemia management recommend tighter LDL-cholesterol (LDL-C) control in order to prevent cardiovascular events. However, it is not yet proven that thigh control of dyslipidaemia, glycaemic levels and body mass index (BMI) in Heart Failure (HF) patients (pts) have an impact on prognosis. Objective To evaluate the impact of LDL-C, HbA1c and BMI values on HF pts mortality and MACE rates. Methods Single centre study that included consecutive pts hospitalized for acute / decompensated chronic HF in a tertiary Hospital between January 2016 to December 2018 and followed for 12 months. The impact of LDL-C, HbA1c and BMI on mortality and MACE was assessed using Cox regression and Kaplan-Meier curve, after adjustment for age, sex, functional class and ejection fraction. A safety cut-off was established when any of these variables was deemed protective using ROC curve analysis. Results Two hundred twenty-four patients (71.68±13.45 years, 63.8% males) were included. Eighty-four (37.5%) pts had type 2 diabetes, 39.7% had ischemic heart disease and the median left ventricular ejection fraction was 34% (IQR 25–49.5; 60.3% HFrEF; 13.8% HFmrEF; 22.3% HFpEF). The median BMI was 25.4 kg/m2 (IQR 23.1–30.5), HbA1c, 6.4% (IQR 5.6–6.8) and LDL-C, 89.5 mg/dL (IQR 64–106); 145 (64.7%) pts were medicated with statins. The overall mortality and MACE rates during follow-up were 16.1% and 21.0%, respectively. According to the CV risk classification 39.7% pts were at very high risk and 19.6% pts at high risk. On multivariate analysis HbA1c (HR 1.5 IQR 1.1–1.9; p=0.007) and female sex (HR 9.453 IQR 2.4–37.2; p=0.001) were independent predictors of mortality, whereas LDL-C (OR 1.05 IQR 1.022–1.075; p&lt;0.001) and BMI (OR 1.23 IQR 1.075–1.404; p=0.002) were independent protective factors. LDL-C and BMI had no effect on MACE rates, although HbA1c was an independent predictor of MACE (HR 1.27 IQR 1.03–1.57; p=0.026). For high and very high-risk pts there was still a protective trend on mortality, although non-significant, for higher levels of LDL-C (OR 1.04 IQR 0.99–1.075; P=NS). Protective LDL-C cut-off were estimated for the whole population (LDL-C 88mg/dL; AUC 0.819; sn 56.6%, sp 100%) and for the high and very-high CV risk pts (LDL-C 84mg/dL; AUC 0.815; sn 59.3%; sp 100%). A BMI safety cut-off for mortality of 25.75 kg/m2 was found (AUC 0.627; sn 61.2%; sp 58.3%). Conclusion This study supports the theory of the obesity and LDL-C paradox in HF. Lower LDL-C and BMI increased mortality and there is no trade-off effect on MACE rates, supporting the idea that LDL-C and BMI should not be aggressively addressed in HF pts. In our cohort a cut-off level of LDL-C below 88mg/dL is associated with higher mortality. On the other hand, diabetes should be actively treated as HbA1c predicts death and MACE in HF pts. Funding Acknowledgement Type of funding source: None


Author(s):  
Jonathan P. Piccini ◽  
Christopher Dufton ◽  
Ian A. Carroll ◽  
Jeff S. Healey ◽  
William T. Abraham ◽  
...  

Background - Bucindolol is a genetically targeted β-blocker/mild vasodilator with the unique pharmacologic properties of sympatholysis and ADRB1 Arg389 receptor inverse agonism. In the GENETIC-AF trial conducted in a genetically defined heart failure (HF) population at high risk for recurrent atrial fibrillation (AF), similar results were observed for bucindolol and metoprolol succinate for the primary endpoint of time to first atrial fibrillation (AF) event; however, AF burden and other rhythm control measures were not analyzed. Methods - The prevalence of ECGs in normal sinus rhythm, AF interventions for rhythm control (cardioversion, ablation and antiarrhythmic drugs), and biomarkers were evaluated in the overall population entering efficacy follow-up (N=257). AF burden was evaluated for 24 weeks in the device substudy (N=67). Results - In 257 patients with HF the mean age was 65.6 ± 10.0 years, 18% were female, mean left ventricular ejection fraction (LVEF) was 36%, and 51% had persistent AF. Cumulative 24-week AF burden was 24.4% (95% CI: 18.5, 30.2) for bucindolol and 36.7% (95% CI: 30.0, 43.5) for metoprolol (33% reduction, p < 0.001). Daily AF burden at the end of follow-up was 15.1% (95% CI: 3.2, 27.0) for bucindolol and 34.7% (95% CI: 17.9, 51.2) for metoprolol (55% reduction, p < 0.001). For the metoprolol and bucindolol respective groups the prevalence of ECGs in normal sinus rhythm was 4.20 and 3.03 events per patient (39% increase in the bucindolol group, p < 0.001), while the rate of AF interventions was 0.56 and 0.82 events per patient (32% reduction for bucindolol, p = 0.011). Reductions in plasma norepinephrine (p = 0.038) and NT-proBNP (p = 0.009) were also observed with bucindolol compared to metoprolol. Conclusions - Compared with metoprolol, bucindolol reduced AF burden, improved maintenance of sinus rhythm, and lowered the need for additional rhythm control interventions in patients with HF and the ADRB1 Arg389Arg genotype.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M A E Haukilahti ◽  
T V Kentta ◽  
J Tikkanen ◽  
O Anttonen ◽  
A Aro ◽  
...  

Abstract Background Heart failure (HF) is one the leading causes of hospitalization in the Western world. Women have a lower rate of HF hospitalization and mortality compared to men. Role of 12-lead electrocardiography (ECG) as a risk marker of future HF in women is not well known. Purpose We studied the association of standard 12-lead ECG and clinical risk factors to HF hospitalization in women and in men separately from a large middle aged general population sample with a long-term follow-up. Methods Standard 12-lead ECG markers were analyzed from 10,864 subjects (48.8% women, N=5,215) of the prospective Mobile Clinic Study, and their predictive value for HF hospitalization was analyzed. Results During the follow-up (29.6±11.2 yrs.), a total of 1,743 subjects had HF hospitalization; out of these, 861 were women (49.4%). Several baseline characteristics, such as age, body mass index, blood pressure, and history of prior cardiac disease predicted the occurrence of HF both in women and men (P<0.001 for all). After adjusting for baseline variables, ECG sign of left ventricular hypertrophy (LVH) (P<0.001), and atrial fibrillation (P<0.001) were the only baseline ECG variables that predicted the future HF in women. In men, HF was predicted by fast heart rate (P=0.008), T wave inversions (P<0.001), abnormal Q waves (P=0.002), and atrial fibrillation (P<0.001). Statistically significant gender interactions in prediction of HF were observed in ECG sign of LVH (P<0.001), inferolateral T wave inversions (P=0.005), and heart rate (P=0.012). Conclusions ECG sign of LVH predicts future HF in middle-aged women independently, and T wave inversions and elevated heart rate are associated with HF hospitalization in men in. Acknowledgement/Funding Finnish Cultural Foundation, The University of Oulu Scholarship Foundation, Juho Vainio Foundation


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Brian D McCauley ◽  
Esseim Sharma ◽  
John Dudley ◽  
Antony Chu

Introduction: Based on the data from CASTLE-AF trial, in patient with Atrial Fibrillation (AF) and heart failure (HF) catheter ablation may offer a significant reduction in both death, and hospitalization, while promoting maintenance of sinus rhythm as well as improvement in left ventricular ejection fraction (LVEF). This multi-center randomized trial is hailed as a paradigm shifting study in catheter ablation, however it is not without fault. One of the critiques of the CASTLE-AF trial was the high frequency of crossover between the treatment arms. To help sort out this potential source of confounding, we performed a systematic meta-analysis of prospective trials for catheter ablation in AF in patients with Class II through IV heart failure. Hypothesis: The reduction in death, and hospitalization, as well as the maintenance in sinus rhythm and improvement in LVEF seen CASTLE-AF trial are support by other similarly designed AF ablation trials. Methods: Using the inclusion/exclusion criteria from the CASTLE-AF trial, we performed a systematic meta-analysis of 28 published studies. Randomized and non-randomized observational studies comparing the impact of catheter ablation of AF in HF. Studies were identified using the Cochrane Library, EMBASE, and PubMed. Results: A total of 29 studies were identified (n =2,339). Mean follow-up was 25 (95% confidence interval, 18-40) months. Efficacy in maintaining sinus rhythm at follow-up end was 60% (43%-76%). Left ventricular ejection fraction improved significantly during follow-up by 15% (P<0.001). Conclusions: Following our meta-analysis, we found data to support the findings of improved LVEF and maintenance of sinus rhythm reported in the CASTLE-AF trial. However, due to differences in study design, we were unable to further validate the reduction in both hospitalization and death seen in CASTLE-AF. We recommend future prospective trials be conducted without cross over to further explore this topic.


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