Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.

BACKGROUND: Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes. METHODS: From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed. RESULTS: 32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively). CONCLUSIONS: Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.

Which dose of apixaban is suitable for Asian patients with atrial fibrillation who have a serum creatinine < 1.5 mg/dL but an estimated glomerular filtration rate < 50 mL/min?

Introduction: Reduced-dose (Low-dose [LD]) apixaban is recommended in patients with atrial fibrillation (AF) who fulfill 2 of 3 criteria: age ≥ 80 years, body weight ≤ 60 kg, and a serum creatinine (sCr) ≥ 1.5 mg/dl. However, the suitable (appropriate) dose for Asian patients who have a sCr < 1.5 mg/dl but an estimated glomerular filtration rate (eGFR) < 50 mL/min is unknown. Methods: This is a retrospective study using the Chang Gung Memorial hospital medical database in Taiwan. A total of 13,508 AF patients receiving oral anticoagulants (OACs) from 2012 to 2018 were reviewed and 1595 patients with a sCr < 1.5 mg/dL and an eGFR < 50 mL/min who met 1 criterion of dose reduction of apixaban other than sCr (that is, age ≥ 80 years or body weight < 60 kg) were identified. Clinical outcomes were compared between LD and SD apixaban versus warfarin. Results: Their OACs use was as follows: 343 receiving apixaban (128 patients on standard dose [SD] and 215 on LD), 174 receiving warfarin, and 1078 on other NOACs. Patients with an eGFR < 50 mL/min had higher risk of mortality (adjusted hazard ratio [aHR], 1.264; 95 % confidence interval [CI], 1.086-1.472) and composite endpoint of 'ischemic stroke/systemic embolism (IS/SE) or major bleeding or mortality (aHR, 1.202; 95 % CI, 1.056-1.370) compared to those with an eGFR ≥ 50 mL/min whereas the risk of IS/SE and major bleeding were similar. LD apixaban was associated with lower risk of composite endpoint of IS/SE or major bleeding (aHR, 0.567; 95 % CI, 0.331 - 0.972), mortality (aHR, 0.336; 95 % CI, 0.138 - 0.815), and 'IS/SE or major bleeding or mortality (aHR, 0.551; 95 % CI, 0343 - 0.886) compared to warfarin while the risk was comparable between SD apixaban and warfarin (aHR, 0.745; 95 % CI, 0.402 - 1.378; aHR, 0.407; 95 % CI, 0.145 - 1.143; aHR, 0.619; 95 % CI, 0.354 - 1.084, respectively). Conclusion: In patients with sCr < 1.5 mg/dL and eGFR < 50 mL/min, SD and LD apixaban were comparable in the prevention of IS/SE, but LD apixaban was superior in reducing the composite endpoint of 'IS/SE or major bleeding or mortality'. Therefore, LD apixaban might be a preferred dose for this population.

The Report of Community-Based and Government-Endorsed Screening Program of Atrial Fibrillation in Taiwan.

BACKGROUND: Although international guidelines recommended opportunistic screening for atrial fibrillation (AF), the community-based AF screening program incorporated into the government-endorsed health care system is rarely reported in Asian countries. OBJECTIVES: We aimed to test the feasibility of adding AF screening into the preexistent adult health check program and report the AF detection rate and percentages of OAC prescriptions before and after AF screening with the involvement of public health care systems. METHODS: We performed this program in three counties (Chiayi county, Keelung City, and Yilan county) in Taiwan which have their own official preexistent adult health check programs conducted by public health bureaus for years. However, electrocardiography (ECG) was not included in these programs before. We cooperated with the public health bureaus of the three counties and performed single-lead 30-second ECG recording for every participant. RESULTS: From January to December 2020, AF screening was performed in 199 sessions with 23,572 participants. AF was detected in 278 subjects with a detection rate of 1.19% (age ≥65 years: 2.39%; ≥75 years: 3.73%). The mean CHA2DS2-VASc score of these 278 subjects was 2.36, with 91% of them had a score ≥1 (males) or ≥2 (females). The number needed to screen was 42 and 27 for subjects aged ≥65 and ≥75 years, respectively. The prescription rate of OACs significantly increased from 11.4 to 60.6% in Chiayi county and from 15.8 to 50.0% in Keelung City after screening (both p-values <0.001). CONCLUSION: This community-based and government-endorsed AF screening project in Taiwan demonstrated that incorporation of AF screening into the preexistent adult health check programs through co-operations with the government was feasible. Actions to detect AF, good education, and well-organized transferring plan after AF being detected with the involvement of public health care systems could result in a substantial increase in the prescription rate of OACs.

Integrated Care for Atrial Fibrillation Using the ABC Pathway in the Prospective APHRS-AF Registry.

Background: The Atrial Fibrillation Better Care (ABC) has been proposed as an integrated approach to improve management in patients with atrial fibrillation (AF), based on 3 pillars: "A" Avoid stroke with Anticoagulation; "B" Better symptoms control; "C" Cardiovascular risk-factor and comorbidities management. Objectives: This study sought to investigate the association with outcomes of ABC adherence in the prospective multinational Asia-Pacific Heart Rhythm Society (APHRS) Atrial Fibrillation registry. Method: Cox-regression analyses adjusted for age, sex, CHA2DS2-VASc score, paroxysmal AF, chronic obstructive pulmonary disease, chronic kidney disease, cancer, dyslipidemia, and dementia were performed to investigate the association with outcomes. Primary outcome was a composite of all-cause death, any thromboembolic events, acute coronary syndrome or percutaneous interventional procedures, and advancing heart failure. Results: Of the 4,013 included patients with AF (mean age 68 ± 12 years; 34.4% female); 38.6% were adherent to all 3 main ABC pillars. After 1 year of follow-up, adherence to the ABC pathway was associated with a low incidence of composite outcome (4.0% vs 8.5%, P < 0.001), all-cause and cardiovascular death, and advancing heart failure. On Cox regression analysis, ABC adherence was associated with a lower risk of primary outcome (HR: 0.72; 95% CI: 0.53-0.97), with risk reduction progressively higher with a higher number of ABC criteria attained. No significant interaction in the association was seen according to the different geographic areas (Pint = 0.217). Conclusions: In a large contemporary cohort of Asian patients with AF, adherence to ABC pathway was associated with a reduction of the risk for adverse outcomes. (Clinical Survey on the Stroke Prevention in Atrial Fibrillation in Asia (AF-Registry; NCT04807049).

Ketogenic diet modulates cardiac metabolic dysregulation in streptozocin-induced diabetic rats.

The ketogenic diet (KD) might improve cardiac function in diabetic cardiomyopathy, but the mechanisms remain unclear. This study investigated the effects of KD on myocardial fatty acid (FA), glucose, and ketone metabolism in diabetic cardiomyopathy. Echocardiograms, biochemistry, and micro-positron emission tomography were performed to evaluate cardiac function and glucose uptake in control rats and streptozotocin-induced diabetes mellitus (DM) rats with normal diet (ND) or KD for 6 weeks. Histopathology, adenosine triphosphate measurement, and Western blot were performed in the ventricular myocytes to analyze fibrosis, FA, ketone body, and glucose utilization. The ND-fed DM rats exhibited impaired left ventricular systolic function and increased chamber dilatation, whereas control and KD-fed DM rats did not. The KD reduced myocardial fibrosis and apoptosis in the DM rats. Myocardial glucose uptake in the micro-positron emission tomography was similar between ND-fed DM rats and KD-fed DM rats and was substantially lower than the control rats. Compared with the control rats,  ND-fed DM rats had increased phosphorylation of acetyl CoA carboxylase and higher expressions of CD-36, carnitine palmitoyltransferase-1ß, tumor necrosis factor-α, interleukin-1ß, interleukin6, PERK, and e-IF2α as well as more myocardial fibrosis and apoptosis (assessed by Bcl-2, BAX, and caspase-3 expression); these increases were attenuated in the KD-fed DM rats. Moreover, ND-fed DM rats had significantly lower myocardial adenosine triphosphate, BHB, and OXCT1 levels than the control and KD-fed DM rats. The KD may improve the condition of diabetic cardiomyopathy by suppressing FA metabolism, increasing ketone utilization, and decreasing endoplasmic reticulum stress and inflammation.

Impact of chronic obstructive pulmonary disease in patients with atrial fibrillation: an analysis from the GLORIA-AF registry.

AIMS: Chronic obstructive pulmonary disease (COPD) may influence management and prognosis of atrial fibrillation (AF), but this relationship has been scarcely explored in contemporary global cohorts. We aimed to investigate the association between AF and COPD, in relation to treatment patterns and major outcomes. METHODS AND RESULTS: From the prospective, global GLORIA-AF registry, we analysed factors associated with COPD diagnosis, as well as treatment patterns and risk of major outcomes in relation to COPD. The primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACEs). A total of 36 263 patients (mean age 70.1 ± 10.5 years, 45.2% females) were included; 2,261 (6.2%) had COPD. The prevalence of COPD was lower in Asia and higher in North America. Age, female sex, smoking, body mass index, and cardiovascular comorbidities were associated with the presence of COPD. Chronic obstructive pulmonary disease was associated with higher use of oral anticoagulant (OAC) [adjusted odds ratio (aOR) and 95% confidence interval (CI): 1.29 (1.13-1.47)] and higher OAC discontinuation [adjusted hazard ratio (aHR) and 95% CI: 1.12 (1.01-1.25)]. Chronic obstructive pulmonary disease was associated with less use of beta-blocker [aOR (95% CI): 0.79 (0.72-0.87)], amiodarone and propafenone, and higher use of digoxin and verapamil/diltiazem. Patients with COPD had a higher hazard of primary composite outcome [aHR (95% CI): 1.78 (1.58-2.00)]; no interaction was observed regarding beta-blocker use. Chronic obstructive pulmonary disease was also associated with all-cause death [aHR (95% CI): 2.01 (1.77-2.28)], MACEs [aHR (95% CI): 1.41 (1.18-1.68)], and major bleeding [aHR (95% CI): 1.48 (1.16-1.88)]. CONCLUSION: In AF patients, COPD was associated with differences in OAC treatment and use of other drugs; Patients with AF and COPD had worse outcomes, including higher mortality, MACE, and major bleeding.

Different Renal Function Equations and Dosing of Direct Oral Anticoagulants in Atrial Fibrillation.

Background: Randomized trials of direct oral anticoagulants (DOACs) adopted the Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of DOACs. Objectives: The authors aimed to investigate the agreements/disagreements of eGFRs calculated using different equations (CG, Modified Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas), and their impacts on the dosages of DOACs and clinical outcomes. Methods: Medical data from a multicenter health care provider in Taiwan including 39,239 patients with atrial fibrillation were used. Among these patients, there were 11,185 and 2,323 patients treated with DOACs and warfarin, respectively. Results: At the cutoff values of eGFR of <15, 15-50, and >50 mL/min, the agreements were 78% between MDRD and CG and 81% between CKD-EPI and CG. The disagreements among the different equations were largely due to overestimations, especially for patients aged >75 years and with a body weight of <50 kg (58.8% for MDRD and 50.9% for CKD-EPI). Among patients receiving DOACs whose dosages were defined as "on label" based on MDRD or CKD-EPI, only those whose dosages were "truly on label" based on CG were associated with a lower risk of major bleeding (adjusted HR: 0.34; 95% CI: 0.26-0.45) compared to warfarin. Conclusions: The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of DOACs (mainly overdosing), which would attenuate the advantages of DOACs compared to warfarin. The CG equation should be used as the gold standard to calculate eGFRs and guide the DOAC dosages.

Risks of Ventricular Tachyarrhythmia and Mortality in Patients with Amyloidosis - A Long-Term Cohort Study.

Background: The presence of ventricular tachycardia (VT) is associated with higher mortality. The annual incidence of VT after a diagnosis of amyloidosis and the associated cardiovascular (CV) outcomes have not been well assessed in a large cohort. Methods: A total of 12,139 amyloidosis patients were identified from the Taiwan National Health Insurance Research Database. Non-amyloidosis group was matched 1:1 for age, gender, hypertension, and diabetes mellitus (DM) to the amyloidosis group using a propensity score. Analysis of the risk of CV outcomes was conducted. We also analyzed the incidence of cardiac amyloidosis (CA). Results: The incidence rates of amyloidosis and CA were 6.54 and 0.61 per 100,000 person-years, respectively. Multivariable analysis revealed that the risk of VT was higher in both the amyloidosis [hazard ratio (HR): 7.90; 95% confidence interval (CI): 4.49-13.9] and CA (HR: 153.3, 95% CI: 54.3-432.7) groups. In the amyloidosis group, the risk of heart failure (HF)-related hospitalization, CV death, and all-cause death was also higher. Amyloidosis was associated with a higher CV mortality rate following VT (HR: 1.50; 95% CI: 1.07-2.12). The onset of a new VT event in patients with amyloidosis was associated with HF, DM, chronic liver disease, and anti-arrhythmic drug use. Conclusions: In this nationwide cohort study, the incidence rates of amyloidosis and CA were 6.54 and 0.61 per 100,000 person-years, respectively. The long-term risks of VT and CV mortality were higher in the patients with amyloidosis and CA. The patients with amyloidosis had a poorer prognosis following VT events, highlighting the importance of continuous monitoring in these patients.

Patterns and Characteristics of SKYLINE-Lumipoint Feature in the Catheter Ablation of Atypical Atrial Flutter: Insight from a Novel Lumipoint Module of Rhythmia Mapping System.

Background: Atypical atrial flutter (aAFL) is not uncommon, especially after a prior cardiac surgery or extensive ablation in atrial fibrillation (AF). Aims: To revisit aAFL, we used a novel Lumipoint algorithm in the Rhythmia mapping system to evaluate tachycardia circuit by the patterns of global activation histogram (GAH, SKYLINE) in assisting aAFL ablation. Methods: Fifteen patients presenting with 20 different incessant aAFL, including two naïve, six with a prior AF ablation, and seven with prior cardiac surgery were studied. Results: Reentry aAFL in SKYLINE typically was a multi-deflected peak with 1.5 GAH-valleys. Valleys were sharp and narrow-based. Most reentry aAFL (18/20, 90%) lacked a plateau and displayed a steep GAH-valley with 2 GAH-valleys per tachycardia. Each GAH-valley highlighted 1.9 areas in the map. Successful sites of ablation all matched one of the highlighted areas based on GAH-valleys < 0.4. These sites corresponded with the areas highlighted by GAH-score < 0.4 in reentry aAFL, and by GAH-score < 0.2 in localized-reentry aAFL. Conclusions: The present study showed benefits of the LumipointTM module applied to the RhythmiaTM mapping system. The results were the efficient detection of the slow conduction, better identification of ablation sites, and fast termination of the aAFL with favorable outcomes.

Prognosis and treatment of atrial fibrillation in Asian cities: 1-year review of the Asia-Pacific Heart Rhythm Society Atrial Fibrillation Registry.

AIMS: The aim of this study is to describe the implementation of the current guidance for stroke prevention and treatment option in atrial fibrillation (AF) and to evaluate mortality and morbidity in relation to therapeutic decisions, including persistence with treatment at 1 year in Asia-Pacific regions. METHODS AND RESULTS: We recruited 4664 patients consecutive in- and outpatients with AF who presented to cardiologists in five countries under the Asia-Pacific Heart Rhythm Society (APHRS) in whom 1-year follow-up was completed for 4003 (65.5% male; mean age 68.5 years). Oral anticoagulant (OAC) use remained high, 77% at follow-up, including 17% prescribed a vitamin K antagonist (VKA) and 60% a non-VKA oral anticoagulant (NOAC). At 1-year follow-up, 93% and 88% remained on a VKA or NOAC, respectively. With good adherence to OAC therapy, 1-year mortality was only 2.7%. Most deaths were non-cardiovascular (72.3%) and the 1-year incidence of stroke/transient ischaemic events (TIA) was low (<1%). Hospital readmissions were common for non-cardiovascular cases and atrial tachyarrhythmias. On multivariate analysis, independent baseline predictors of mortality and/or stroke/TIA/peripheral embolism were age, previous heart failure for >12 months, and malignancy. Independent predictors of mortality were age, chronic obstructive pulmonary disease, malignancy, and diuretic use. AF as a primary presentation was predictive of lower mortality and/or stroke/TIA/peripheral embolism as well as mortality. CONCLUSION: In this 1-year analysis of the APHRS-AF registry, overall OAC use and persistence were high and were associated with low 1-year cardiovascular mortality and morbidity, but mortality and morbidity related to non-cardiovascular causes were high in AF patients, particularly from malignancy and pneumonia.

Catheter Ablation in Arrhythmic Cardiac Diseases: Endocardial and Epicardial Ablation.

Arrhythmogenic cardiomyopathy (ACM) is a group of arrhythmogenic disorders of the myocardium that are not caused by ischemic, hypertensive, or valvular heart disease. The clinical manifestations of ACMs may overlap those of dilated cardiomyopathy, complicating the differential diagnosis. In several ACMs, ventricular tachycardia (VT) has been observed at an early stage, regardless of the severity of the disease. Therefore, preventing recurrences of VT can be a clinical challenge. There is a wide range of efficacy and side effects associated with the use of antiarrhythmic drugs (AADs) in the treatment of VT. In addition to AADs, patients with ACM and ventricular tachyarrhythmias may benefit from catheter ablation, especially if they are drug-refractory. The differences in pathogenesis between the various types of ACMs can lead to heterogeneous distributions of arrhythmogenic substrates, non-uniform ablation strategies, and distinct ablation outcomes. Ablation has been documented to be effective in eliminating ventricular tachyarrhythmias in arrhythmogenic right ventricular dysplasia (ARVC), sarcoidosis, Chagas cardiomyopathy, and Brugada syndrome (BrS). As an entity that is rare in nature, ablation for ventricular tachycardia in certain forms of ACM may only be reported through case reports, such as amyloidosis and left ventricular noncompaction. Several types of ACMs, including ARVC, sarcoidosis, Chagas cardiomyopathy, BrS, and left ventricular noncompaction, may exhibit diseased substrates within or adjacent to the epicardium that may be accountable for ventricular arrhythmogenesis. As a result, combining endocardial and epicardial ablation is of clinical importance for successful ablation. The purpose of this article is to provide a comprehensive overview of the substrate characteristics, ablation strategies, and ablation outcomes of various types of ACMs using endocardial and epicardial approaches.

Arrhythmogenic right ventricular cardiomyopathy: diverse substrate characteristics and ablation outcome.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy caused by defective desmosomal proteins. The typical histopathological finding of ARVC is characterized by progressive fibrofatty infiltration of the right ventricle due to the dysfunction of cellular adhesion molecules, thus, developing arrhythmogenic substrates responsible for the clinical manifestation of ventricular tachycardia/fibrillation (VT/VF). Current guidelines recommend implantable cardiac defibrillator (ICD) implantation to prevent sudden cardiac death (SCD) in ARVC, especially for those experiencing VT/VF or aborted SCD, while antiarrhythmic drugs, despite their modest effectiveness and several undesirable adverse effects, are frequently used for those experiencing episodes of ICD interventions. Given the advances in mapping and ablation technologies, catheter ablation has been implemented to eliminate drug-refractory VT in ARVC. A better understanding of the pathogenesis, underlying arrhythmogenic substrates, and putative VT isthmus in ARVC contributes to a significant improvement in ablation outcomes through comprehensive endocardial and epicardial approaches. Regardless of ablation strategies, there is a diversity of arrhythmogenic substrates in ARVC, which could partly explain the nonuniform ablation outcome and long-term recurrences and reflect the role of potential factors in the modification of disease progression and triggering of arrhythmic events.

Prediction of Recurrent Atrial Tachyarrhythmia After Receiving Atrial Flutter Ablation in Patients With Prior Cardiac Surgery for Valvular Heart Disease.

Background: Surgical scars cause an intra-atrial conduction delay and anatomical obstacles that facilitate the perpetuation of atrial flutter (AFL). This study aimed to investigate the outcome and predictor of recurrent atrial tachyarrhythmia after catheter ablation in patients with prior cardiac surgery for valvular heart disease (VHD) who presented with AFL. Methods: Seventy-two patients with prior cardiac surgery for VHD who underwent AFL ablation were included. The patients were categorized into a typical AFL group (n = 45) and an atypical AFL group (n = 27). The endpoint was the recurrence of atrial tachyarrhythmia during follow-up. A multivariate analysis was performed to determine the predictor of recurrence. Results: No significant difference was found in the recurrence rate of atrial tachyarrhythmia between the two groups. Patients with concomitant atrial fibrillation (AF) had a higher recurrence of typical AFL compared with those without AF (13 vs. 0%, P = 0.012). In subgroup analysis, typical AFL patients with concomitant AF had a higher incidence of recurrent atrial tachyarrhythmia than those without it (53 vs. 14%, P = 0.006). Regarding patients without AF, the typical AFL group had a lower recurrence rate of atrial tachyarrhythmia than the atypical AFL group (14 vs. 40%, P = 0.043). Multivariate analysis showed that chronic kidney disease (CKD) and left atrial diameter (LAD) were independent predictors of recurrence. Conclusions: In our study cohort, concomitant AF was associated with recurrence of atrial tachyarrhythmia. CKD and LAD independently predicted recurrence after AFL ablation in patients who have undergone cardiac surgery for VHD.

Mortality associated with the use of non-vitamin K antagonist oral anticoagulants in cancer patients: Dabigatran versus rivaroxaban.

OBJECTIVE: This study assesses the mortality outcomes of non-vitamin K antagonist oral anticoagulants (NOACs) in cancer patients with venous thromboembolism (VTE) and atrial fibrillation (AF). METHODS: Medical records of cancer patients receiving NOACs for VTE or AF between January 1, 2011, and December 31, 2016, were retrieved from Taiwan's National Health Institute Research Database. NOACs were compared using the inverse probability of treatment weighting (IPTW) method. The primary outcome was cancer-related death. Secondary outcomes were all-cause mortality, major bleeding, and gastrointestinal (GI) bleeding. RESULTS: Among 202,754 patients who received anticoagulants, 3591 patients (dabigatran: 907; rivaroxaban: 2684) with active cancers were studied. Patients who received dabigatran were associated with lower risks of cancer-related death at one year (HR = 0.71, 95% CI = 0.54-0.93) and at the end of follow-ups (HR = 0.79, 95% CI = 0.64-0.98) compared with rivaroxaban. Patients who received dabigatran were also associated with lower risks of all-cause mortality (HR = 0.81, 95% CI = 0.67-0.97), major bleeding (HR = 0.64, 95% CI = 0.47-0.88), and GI bleeding (HR = 0.57, 95% CI = 0.39-0.84) at the end of follow-ups compared with rivaroxaban. CONCLUSION: Compared with rivaroxaban, the use of dabigatran may be associated with a lower risk of cancer-related death and all-cause mortality.

Clinical Outcomes in Atrial Fibrillation Patients With a History of Cancer Treated With Non-Vitamin K Antagonist Oral Anticoagulants: A Nationwide Cohort Study.

Background and Purpose: Data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in patients with atrial fibrillation and cancer are limited, and patients with active cancer were excluded from randomized trials. We investigated the effectiveness and safety for NOACs versus warfarin among patients with atrial fibrillation with cancer. Methods: In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database, we identified a total of 6274 and 1681 consecutive patients with atrial fibrillation with cancer taking NOACs and warfarin from June 1, 2012, to December 31, 2017, respectively. Propensity score stabilized weighting was used to balance covariates across study groups. Results: There were 1031, 1758, 411, and 3074 patients treated with apixaban, dabigatran, edoxaban, and rivaroxaban, respectively. After propensity score stabilized weighting, NOAC was associated with a lower risk of major adverse cardiovascular events (hazard ratio, 0.63 [95% CI, 0.50­0.80]; P=0.0001), major adverse limb events (hazard ratio, 0.41 [95% CI, 0.24­0.70]; P=0.0010), venous thrombosis (hazard ratio, 0.37 [95% CI, 0.23­0.61]; P<0.0001), and major bleeding (hazard ratio, 0.73 [95% CI, 0.56­0.94]; P=0.0171) compared with warfarin. The outcomes were consistent with either direct thrombin inhibitor (dabigatran) or factor Xa inhibitor (apixaban, edoxaban, and rivaroxaban) use, among patients with stroke history, and among patients with different type of cancer and local, regional, or metastatic stage of cancer (P interaction >0.05). When compared with warfarin, NOAC was associated with lower risk of major adverse cardiovascular event, and venous thrombosis in patients aged <75 but not in those aged ≥75 years (P interaction <0.05). Conclusions: Thromboprophylaxis with NOACs rather than warfarin should be considered for the majority of the atrial fibrillation population with cancer.

Deep Sedation with Intravenous Anesthesia Is Associated with Outcome in Patients Undergoing Cryoablation for Paroxysmal Atrial Fibrillation.

Whether deep sedation with intravenous anesthesia will affect the recurrence after cryoballoon ablation (CBA) of paroxysmal atrial fibrillation (AF) is yet to be examined. Thus, in this study, we hypothesize that there is difference in terms of the recurrence between local anesthesia and deep sedation with intravenous anesthesia after an index ablation procedure.In total, 109 patients were enrolled and received CBA, of which 68 (58.2 years) patients underwent pulmonary vein (PV) isolation with a local anesthesia (group 1) and 41 patients (63.2 years) underwent PV isolation with deep sedation using intravenous anesthesia (group 2).During the index procedure, isolation of all major PVs was achieved in 66 patients in group 1 and in 41 patients in group 2. There was no difference in non-PV triggers between the two groups. The periprocedural complication was found to be similar between the two groups (2.9% in group 1 and 4.9% in group 2). Further, 17 patients in group 1 and 4 patients in group 2 experienced recurrences after a follow-up of 19.3 months (P = 0.019). Repeat procedures revealed similar PV reconnection rates between the two groups. It has also been noted that the number of reconnected PV and incidence of atypical flutter seem to increase in group 1.Deep sedation with intravenous anesthesia during CBA for paroxysmal AF is safe and had a better long-term outcome than those with local anesthesia.

Mechanism of angiotensin receptor-neprilysin inhibitor in suppression of ventricular arrhythmia.

BACKGROUND: The mechanisms underlying angiotensin receptor-neprilysin inhibitor (ARNi) suppression of ventricular arrhythmia (VA) are unclear. This study aimed to investigate the mechanism of ARNi-related suppression of VA in a heart failure (HF) model. METHODS: New Zealand white rabbits (n = 6 per group) were assigned to normal, HF [4 weeks of left ascending artery (LAD) ligation], angiotensin receptor blocker (ARB, valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation), and ARNi (sacubitril at 34 mg/kg/day and valsartan at 27 mg/kg/day for 3 weeks after 1 week of LAD ligation) groups. Experiments involving echocardiogram, optical mapping, histological of trichrome stain and immunostain, and flow cytometry were performed. RESULTS: HF group had larger left ventricular (LV) internal dimensions in diastole and systole, and lower LV ejection fraction and fractional shortening than normal, ARB, and ARNi groups. HF group had a prolonged action potential duration (APD) and decreased conduction velocity (CV), which was mitigated in ARB and ARNi groups. HF group had a prolonged QRS duration, QT and QTc intervals, which was reversed in ARB and ARNi groups. HF group had a steeper maximum slope of APD restitutions, which was attenuated in normal, ARB, and ARNi groups. HF group had increased number of phase singularities (PSs) and VA inducibility than normal, ARB, and ARNi groups. A higher content of fibrosis was found in HF group than that in normal, ARB, and ARNi groups. Compared to ARB group, ARNi had a lower context of fibrosis. HF group had more peripheral blood CD4+ and CD8+ cells count than normal, ARB, and ARNi group. CONCLUSIONS: In a rabbit model of ischemic HF, ventricular arrhythmogenesis could be suppressed by ARNi treatment. This appears to be mediated by reversing changes in the APD, CV, maximum slope of the APDR, PSs, fibrosis, and inflammation.

Optimal Management of Anticoagulation Therapy in Asian Patients With Atrial Fibrillation.

Stroke prevention is the cornerstone of management of atrial fibrillation (AF), and non-vitamin K antagonist oral anticoagulants (NOACs) are commonly prescribed. Because routine monitoring of anticoagulant effects of NOACs is not necessary, appropriate dosing following the criteria of each NOACs defined in pivotal randomized trials is important. Real-world data demonstrate that underdosing NOACs is associated with a higher risk of ischemic stroke without a lower risk of major bleeding. Furthermore, renal function of AF patients should be assessed using the Cockcroft-Gault formula to prevent overestimation that could result in overdosing of NOACs. The assessment of bleeding risk is important, and the HAS-BLED score should be used to help identify patients at high risk of bleeding (HAS-BLED score ≥3). Moreover, the HAS-BLED score should be reassessed at periodic intervals to address potentially modifiable bleeding risk factors because bleeding risks of AF patients are not static. When managing NOAC-related bleeding episodes, the possibility of occult malignancies (e.g., grastrointestinal [GI] tract cancers for patients experiencing GI bleeding and bladder cancer for patients with hematuria) should be kept in mind. Addressing all of these issues is crucial to achieving better clinical outcomes for anticoagulated AF patients. More efforts are necessary to incorporate clear and easy-to-follow recommendations about optimal management of anticoagulation into the guidelines to improve AF patient care.

Case series on stereotactic body radiation therapy in non-ischemic cardiomyopathy patients with recurrent ventricular tachycardia.

INTRODUCTION: The efficacy of stereotactic body radiation therapy (SBRT) as an alternative treatment for recurrent ventricular tachycardia (VT) is still unclear. This study aimed to report the outcome of SBRT in VT patients with nonischemic cardiomyopathy (NICM). METHODS: The determination of the target substrate for radiation was based on the combination of CMR results and electroanatomical mapping merged with the real-time CT scan image. Radiation therapy was performed by Flattening-filter-free (Truebeam) system, and afterward, patients were followed up for 13.5 ± 2.8 months. We analyzed the outcome of death, incidence of recurrent VT, ICD shocks, anti-tachycardia pacing (ATP) sequences, and possible irradiation side-effects. RESULTS: A total of three cases of NICM patients with anteroseptal scar detected by CMR. SBRT was successfully performed in all patients. During the follow-up, we found that VT recurrences occurred in all patients. In one patient, it happened during a 6-week blanking period, while the others happened afterward. Re-hospitalization due to VT only appeared in one patient. Through ICD interrogation, we found that all patients have reduced VT burden and ATP therapies. All of the patients died during the follow-up period. Radiotherapy-related adverse events did not occur in all patients. CONCLUSIONS: SBRT therapy reduces the number of VT burden and ATP sequence therapy in NICM patients with VT, which had a failed previous catheter ablation. However, the efficacy and safety aspects, especially in NICM cases, remained unclear.

The isthmus characteristics of scar-related macroreentrant atrial tachycardia in patients with and without cardiac surgery.

INTRODUCTION: Identifying the critical isthmus (CI) in scar-related macroreentrant atrial tachycardia (AT) is challenging, especially for patients with cardiac surgery. We aimed to investigate the electrophysiological characteristics of scar-related macroreentrant ATs in patients with and without cardiac surgery. METHODS: A prospective study of 31 patients (mean age 59.4 ± 9.81 years old) with scar-related macroreentrant ATs were enrolled for investigation of substrate properties. Patients were categorized into the nonsurgery (n = 18) and surgery group (n = 13). The CIs were defined by concealed entrainment, conduction velocity less than 0.3 m/s, and the presence of local fractionated electrograms. RESULTS: Among the 31 patients, a total of 65 reentrant circuits and 76 CIs were identified on the coherent map. The scar in the surgical group is larger than the nonsurgical group (18.81 ± 9.22 vs. 10.23 ± 5.34%, p = .016). The CIs in surgical group have longer CI length (15.27 ± 4.89 vs. 11.20 ± 2.96 mm, p = .004), slower conduction velocity (0.46 ± 0.19 vs. 0.69 ± 0.14 m/s, p < .001), and longer total activation time (45.34 ± 9.04 vs. 38.24 ± 8.41%, p = .016) than those in the nonsurgical group. After ablation, 93.54% of patients remained in sinus rhythm during a follow-up of 182 ± 19 days. CONCLUSION: The characteristics of the isthmus in macroreentrant AT are diverse, especially for surgical scar-related AT. The identification of CIs can facilitate the successful ablation of scar-related ATs.