Association between CHADS2, CHA2DS2-VASc, ATRIA, and Essen Stroke Risk Scores and Unsuccessful Recanalization after Endovascular Thrombectomy in Acute Ischemic Stroke Patients

Background: The CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT). Methods: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient. Results: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198–2.009, p = 0.001; CHA2DS2VASc score: OR 1.269, 95% CI 1.080–1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011–1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167–1.849, p = 0.001). The CHADS2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS2 score; 0.618, 95% CI 0.554–0.681). Conclusion: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

Effectiveness and safety of edoxaban in atrial fibrillation patients from the ETNA-AF global registry

Background/Introduction ETNA-AF (ETNA) is a multinational, prospective, observational study evaluating the experience with edoxaban in the clinical practice of patients with atrial fibrillation (AF). ENGAGE AF-TIMI 48 was a randomized double-blind trial that tested the clinical benefits of edoxaban versus warfarin. The recommended dose is 60 mg, dose-reduced to 30 mg daily in patients with at least 1 of 3 label-indicated criteria (renal impairment [creatinine clearance: 15–≤50 mL/min], weight ≤60 kg, or concomitant use of potent P-glycoprotein inhibitors). Purpose We assessed whether the effectiveness and safety of edoxaban in clinical practice were consistent with findings from the pivotal randomized clinical trial. Methods We obtained patient-level data from ETNA and ENGAGE AF-TIMI 48. We initially extracted patients from similar geographic regions, and then used propensity-score matching (PSM) to adjust key baseline characteristic differences between studies. The primary effectiveness endpoint was all stroke or systemic embolism (SSE) and mortality; the safety endpoint was major bleeding (MB). We used Cox proportional hazards models to compare event rates for the clinical outcomes between ETNA and ENGAGE AF-TIMI 48. Results 8,615 AF patients with CHADS2 score ≥2 received the 60 mg edoxaban recommended dose (5,462 ETNA; 3,153 ENGAGE AF-TIMI 48). After PSM, key baseline characteristics were well-balanced between the studies: mean age 71.0 years (SD: 9.07); for both ETNA and ENGAGE AF-TIMI 48 median CHA2DS2-VASc score and median HAS-BLED score were 4 and 2. The annualized incidence rate of SSE was 1.65% in ETNA vs 1.53% in ENGAGE AF-TIMI 48 (HR 0.98; 95% CI 0.49, 1.93; p=0.94). ETNA had similar annualized mortality, 2.81%, compared with ENGAGE AF-TIMI 48, 2.34%, (HR 1.49; 95% CI 0.84, 2.63; p=0.17). MB was less frequent in ETNA vs ENGAGE AF-TIMI 48 (1.10% vs 3.56%; HR 0.25; 95% CI 0.14, 0.44; p&lt;0.05). Findings were similar for the recommended 30 mg edoxaban reduced dose. Conclusions The effectiveness of edoxaban in clinical practice from a large registry was consistent with efficacy findings from the randomized controlled trial. We observed a lower rate of bleeding events in the ETNA observational study compared with the ENGAGE AF-TIMI 48 trial. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was sponsored by Daiichi Sankyo Inc.

Predictive value of CHA2DS2-VASc score combined with hs-CRP for new-onset atrial fibrillation in elderly patients with acute myocardial infarction

Background New-onset atrial fibrillation (NOAF) is common during acute myocardial infarction (AMI) and independently associated with worse prognosis. We aimed to validate the discrimination performance of CHA2DS2-VASc score combined with hs-CRP in the prediction of NOAF after AMI in elderly Chinese population. Methods 311 consecutive elderly patients (age ≥ 65 years old) with AMI from 1 January 2018 to 1 January 2019 without atrial fibrillation history were enrolled in our study. Univariable and multivariable logistic regression analyses were used to identify risk factors of NOAF. The discrimination performance of different score models were evaluated using ROC curve analysis and AUCs were compared using the Z test. Results 30 (9.65%) patients developed NOAF during hospitalization. The NOAF group were older and had higher hs-CRP, initial Killip class, BNP, LAD, CHADS2 score, CHA2DS2-VASc score, in-hospital mortality and lower LVEF and ACEI/ARB use (P < 0.05 vs group without NOAF for all measures). In multivariate regression analyses, age (OR = 1.127, 95% CI 1.063–1.196, P < 0.001) and hs-CRP (OR = 1.034, 95% CI 1.018–1.05, P < 0.001) were independent predictors of NOAF. In ROC curve analyses, both CHADS2 score (AUC = 0.624, 95% CI 0.516–0.733, P = 0.026) and CHA2DS2-VASc score (AUC = 0.687, 95% CI 0.584–0.79, P = 0.001) had acceptable but unsatisfactory discrimination performance in predicting NOAF after AMI. The combined model with CHA2DS2-VASc score and hs-CRP showed a significant better predictive value (AUC = 0.791, 95% CI 0.692–0.891, P < 0.001) compared to that of the CHA2DS2-VASc score alone (Z test, P = 0.008). Conclusion The combined model with CHA2DS2-VASc score and hs-CRP had high accuracy in predicting post-AMI NOAF.

The safety of catheter ablation of atrial fibrillation in elderly patients -analysis of the nationwide database in Japan, JROAD-DPC-

Background “Age” is one of the major concerns and determinants of the indications for catheter ablation (CA) of atrial fibrillation (AF). There are little safety data on CA of AF according to the age. This study aimed to assess the safety of CA in elderly patients undergoing CA of AF. Methods and results We investigated the complication rate of CA of AF for the different age groups (&lt;60 years, 60–65, 65–70, 70–75, 75–80, 80–85, and ≥85) by a nationwide database (Japanese Registry Of All cardiac and vascular Diseases [JROAD]-DPC). The JROAD-DPC included 73,296 patients (65±11 years, 52,883 men) who underwent CA of AF from 516 hospitals in Japan. Aged patients had more comorbidities and a significantly increased CHADS2 score and higher rate of female according to a higher age. The overall complication rate was 2.6% and in-hospital mortality was 0.05%. By comparing each age group, complications occurred more frequently in higher aged groups. A multivariate adjusted hazard ratio revealed an increased age was independently and significantly associated with the overall complications (odds ratio was 1.25, 1.35, 1.72, 1.86, 2.76 and 3.13 respectively; reference &lt;60 years). Conclusions The frequency of complications was significantly higher according to a higher age. We should take note of the indications and procedure for CA of AF in aged patients. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Intramural Research Fund 17 (Kusano) for Cardiovascular Diseases of the National Cerebral and Cardiovascular Center

Presence of low voltage area predicts atrial tachyarrhythmia inducibility with atrial burst pacing after pulmonary vein isolation

Background Induction of atrial fibrillation (AF)/atrial tachycardia (AT) by atrial burst pacing following ablation procedure may reflect the presence of residual substrates in the atria that maintain AF. However, the relation between the inducibility and left atrial low voltage area (LVA) has not been established. Methods Fifty-nine patients (65 years old, 43 males) with persistent AF who underwent pulmonary vein isolation (PVI)-based ablation were studied. All patients underwent left atrial voltage mapping during sinus rhythm and atrial burst pacing after PVI. Atrial burst pacing was performed with 30-beat at an amplitude of 10V from the ostium of the coronary sinus; increasing from 240 to 320 ppm in steps of 20 ppm or failure to 1:1 atrial capture. Inducibility was defined as AF/AT lasting more than 5 minutes following burst pacing. Left atrial LVA and other co-variates were analyzed with regard to burst pacing positivity. Results AF/AT was induced by burst pacing in 23 patients (39%). Univariate analysis revealed that past history of stroke, CHADS2 score and presence of left atrial LVA were significantly associated with the inducibility of AF/AT. Multivariate analysis revealed that only the presence of LVA was associated with the inducibility (OR 1.5: per 10% increase; p=0.04). We focused on the relationship between the extent of LVA and burst positivity. AF/AT inducibility increased as low voltage area increased, and it was as high as 72.7% when low voltage area was more than 20% (P&lt;0.05). Interestingly, induced arrhythmia type was AT rather than AF when low voltage area was more than 20%. Conclusions Presence of left atrial LVA is an independent predictor of atrial tachyarrhythmia inducibility after PVI in patients with persistent AF. A large amount of low voltage area is related to AT inducibility rather than AF. Extent of LVA and burst positivity Funding Acknowledgement Type of funding source: None

Serial measurement of biomarkers and the risk of stroke or systemic embolism and bleeding in patients with atrial fibrillation in ENGAGE AF-TIMI 48

Background Patients with atrial fibrillation (AF) have progressive cardiac structural changes that may be manifest by biomarkers of myocardial injury and hemodynamic stress. Baseline values of hsTnT (high-sensitivity troponin T), and NT-proBNP (N-terminal pro-brain natriuretic peptide) are associated with stroke risk and GDF-15 (growth differentiation factor-15) is associated with bleeding risk in patients with AF. However, the variability of these biomarkers over time and their associations with stroke or systemic embolism events (S/SEE) and bleeding in patients with AF remain unclear. Purpose We examined whether patients with AF demonstrate detectable changes in these biomarkers over 12 months and whether such changes from baseline to 12 months are associated with the subsequent risk of S/SEE (hsTnT, NT-proBNP) and bleeding (GDF-15). Methods ENGAGE AF-TIMI 48 was a multinational randomized trial of the oral factor Xa inhibitor edoxaban in patients with atrial fibrillation and a CHADS2 score ≥2. We performed a nested prospective biomarker study in 6062 patients, analyzing hsTnT, NT-proBNP, and GDF-15 at baseline and 12 months. Event rates were estimated and displayed with annualized event rates after 12 months. Results Of 6062 patients, hsTnT was dynamic in 46.9% (≥2 ng/L change), NT-proBNP in 51.9% (≥200 pg/L change), GDF-15 in 45.6% (≥300 pg/L change) between baseline and 12 months. In addition, 7.7% in hsTnT shifted from low-&gt;high categories, 9.4% in NT-proBNP from low-&gt;high, 10.6% in GDF-15 from low-&gt;high over 12 months (Figure). Elevated hsTnT (≥14 ng/L) and NT-proBNP (≥900 pg/L) either at baseline or at 12 months were independently associated with higher rates of subsequent S/SEE, and elevated GDF-15 (≥1800 pg/L) either at baseline or at 12 months were independently associated with higher rates of subsequent bleeding (P&lt;0.001 for each). In a Cox regression model, the absolute changes in log2-transformed hsTnT and NT-proBNP were associated with increased risk of S/SEE (adj-HR, 1.75; 95% CI, 1.38–2.23; p&lt;0.001, and adj-HR, 1.31; 95% CI, 1.11–1.55; p=0.002, respectively) and log2-transformed GDF-15 with bleeding (adj-HR, 1.42; 95% CI, 1.04–1.92; p=0.025). Analyzed in a categorical manner (Figure), patients who increased hsTnT or NT-proBNP between baseline and 12 months or had high hsTnT or NT-proBNP at both timepoints were at higher risk for S/SEE (adj-HR 1.87 and 1.50 for hsTnT; adj-HR 1.80 and 2.59 for NT-proBNP, respectively). Patients with persistently elevated GDF-15 appeared to be at higher risk for bleeding (adj-HR,1.35) (Figure). Conclusions Serial assessment of hsTnT, NT-proBNP, and GDF-15 revealed a substantial proportion of patients with AF had dynamic values. Patients with either persistently elevated or dynamic values were at higher risk of adverse clinical outcomes. Those biomarkers may play a role in personalizing preventive strategies in patients with AF based on risk. Change in biomarkers and event rate Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo Pharma Development

Predictors of silent cerebral infarction associated with catheter ablation for atrial fibrillation

Introduction Cather ablation (CA) has been identified as an effective and safe treatment option for patients with atrial fibrillation (AF). One of the serious complications associated AF is cerebral infarction (CI). Recent studies reported that CA was associated with lower incidence of ischemic stroke in patients with AF. However, CA for AF itself has a potential risk of CI. Several previous studies showed that the incidence of silent CI (SCI) assessed by magnetic resonance imaging (MRI) of the brain occurred 5 to 18% during CA for AF. Recently, CA for AF made a remarkable progress in technology. However, there are few information available that the impact of 3-dimensional electroanatomical mapping system on the incidence of SCI. This study aimed to clarify the prevalence and predictors of SCI during CA for AF. Methods We enrolled 893 consecutive patients (male 534, age 71±10 years), who underwent CA for AF and MRI of brain 1 day after the procedure. We collected patients data such as physical examinations, blood sampling, echo cardiography, and CA data. A brain MRI was performed the next day following the procedure to identify any CIs. One-hundred and forty-six of patients used the Rhythmia® mapping system catheter, and the other mapping system such as CARTO or EnSite system used in the remaining 747 patients. Results The MRI depicted acute micro-CIs in 144 (16%) patients, but neither symptoms nor abnormal neurological findings were present in these patients. Patients with SCI had significantly higher prevalence of persistent AF (60 vs 43%, p=0.0002), CHADS2 Score (2 (1–3) vs 1 (1–2), p=0.0001), higher prevalence of previous stroke (19 vs 12%, p=0.02), larger left atrial (LA) diameter (43.2±6.4 vs 41.7±6.5mm, p=0.01), lower left ventricular ejection fraction (LVEF) (59.0±13.2 vs 64.2±11.3%, p≤0.0001), higher B-type natriuretic peptide level (221±236 vs 163±225 pg/dl, p≤0.0001), more Rhythmia® mapping system use (30 vs 8%, p&lt;0.0001), and longer procedure time (129±46 vs 108±39 min, p≤0.0001) than those without SCI, while there were no significant differences in age, LA appendage flow velocity, kind of anti-coagulant agent between the two groups. Multivariate regression analysis identified Rhythmia® use [odds ratio (OR) 4.26, (95% CI 2.32–7.84), p=0.0001], LVEF (OR 1.02, p=0.0059), CHADS2 score (OR 1.27, p=0.009), and procedure time (OR 1.005, p=0.04) as independent risk factors of acute SCI during CA for AF. Conclusion Acute SCI occurred about 16% after CA for AF. Rhythmia® mapping system use exhibited a higher incidence of acute SCI after catheter ablation for AF than the other mapping system use. Rhythmia® mapping system use, LVEF, CHADS2 score, and procedure time are associated with SCI relating CA for AF. Funding Acknowledgement Type of funding source: None

Validation and comparison of six risk scores for post acute myocardial infarction infection

Background Various risk scores have been proven to predict outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). However, few of them were validated and compared the difference of the prediction of infection during hospitalization in such patients. Aim We aimed to validate and compare the discriminatory value of different risk scores for predicting infection. Methods Patients who were diagnosed with STEMI treated with PCI were enrolled from January 2010 to May 2018. The six risk scores included the Age, Serum Creatinine (SCr), or Glomerular Filtration Rate, and Ejection Fraction (ACEF or AGEF) score, Canada Acute Coronary Syndrome Risk Score (CACS score), CHADS2 score, Global Registry for Acute Coronary Events (GRACE) score and Mehran score. The primary end point was infection during hospitalization. The secondary endpoint was major adverse clinical events including all cause death, stroke and any bleeding. The prognostic accuracy of the six scores was assessed using the c statistic for discrimination and the Hosmer-Lemeshow test for calibration. Results A total of 2260 eligible patients were enrolled (62.32±12.36 year, 81.3% of males). A significant gradient of risk with respect to infection and in hospital major adverse clinical events (MACE) was observed with increasing all six risk scores. Other than the CHADS2 score (AUC: 0.682; 95% CI, 0.652–0.712), other five risk scores showed the good discrimination for predicting infection, with the GRACE score being the best (AUC: 0.791; 95% CI, 0.765–0.817). In addition, all risk scores showed best calibration for infection, but good calibration for CACS risk score (calibration slope: 0.77, 95% CI: 0.18–1.35) (Figure 1). Furthermore, each score showed a best discrimination for in hospital MACE, with AUCs ranging from 0.761 to 0.786, other than CACS risk score and CHADS2 risk score with AUC of 0.700 and 0.696, respectively. All risk scores showed best calibration for in hospital MACE. Conclusions In patients with STEMI undergoing PCI, these risk scores (ACEF, AGEF, CACS, GRACE and Mehran) showed good discrimination and calibration to predict infection and MACE. The CACS score was recommended for clinical use as its clinical variables were simple and practical. Figure 1 Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Science Foundation for Young Scientists of China

CHA2DS2-VASc and CHADS2 scores for risk stratification of major adverse cardiovascular events in the COMPASS trial

Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial demonstrated that the combination therapy of rivaroxaban and aspirin reduced major adverse cardiovascular events (MACE) compared to aspirin alone in patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD). Purpose We assessed whether the CHA2DS2-VASc (congestive heart failure (CHF), hypertension, age ≥75 years, diabetes, stroke/transient ischemic attack (TIA)/thromboembolism, vascular disease, age 65–75 years, and sex category) and CHADS2 (CHF, hypertension, age ≥75 years, diabetes, stroke/TIA) scores used to predict the risk of stroke in patients with atrial fibrillation, can be used identify vascular patients at highest risk of recurrent events who may derive greatest benefits of treatment. Methods In COMPASS patients, the predictive accuracy of CHA2DS2-VASc and CHADS2 scores were assessed for MACE, bleeding and net clinical benefit using Cox proportional hazards model. Kaplan-Meier estimates of cumulative risk and absolute risk differences were used to examine the effects of rivaroxaban plus aspirin compared with aspirin alone over 30 months according to risk score categories. Results In 27,395 participants with CAD and/or PAD, a high CHA2DS2-VASc score (6–9) was associated with 3 times greater absolute risk of MACE compared to a low score (1–2) (hazard ratio=3.39, 95% CI: 2.54–4.51, p&lt;0.0001). The effects of combination therapy with rivaroxaban and aspirin on MACE, bleeding and net clinical benefit were consistent across CHA2DS2-VASc and CHADS2 score categories, with the greatest benefit in those with the highest risk scores (Figure 1). The greatest reduction in MACE with rivaroxaban and aspirin compared to aspirin only was observed in patients treated for 30 months with highest CHA2DS2-VASc score (6–9) (23 events per 1000 patients prevented) or highest CHADS2 score (3–6) (25 events per 1000 patients prevented). There was increased bleeding in patients with higher CHA2DS2-VASc and CHADS2 scores, but net clinical benefit was preserved across all risk categories and was greatest in those with the highest risk scores. Conclusion The CHA2DS2-VASc or CHADS2 scores can be used in patients with chronic CAD and/or PAD to identify patients who are at highest risk of MACE, and therefore likely to achieve the greatest benefit of dual pathway inhibition with the combination of rivaroxaban and aspirin compared with aspirin alone. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): This study was sponsored by Bayer AG.

Is implantable loop recorder the answer to reduce the increased risk of stroke in cancer patients?

Introduction Recent epidemiologic data suggests increased risk of ischaemic stroke in cancer patients. The etiology of increased ischaemic stroke is unknown. Atrial fibrillation (AF) is among the potential etiologies. The risk of AF has not been studied among cancer patients in the United States. Purpose Ascertain the association of AF in cancer patients in the USA by using the largest database i.e. National Inpatient Sample (NIS). Methods Patients ≥18 years old were selected in the NIS database for years 2010 to 2014 and stratified based on presence or absence of any of four cancers (lung, colon, breast and prostate; 4CA) using ICD 9 codes. Atrial fibrillation and stroke/TIA were also identified using ICD 9 codes. Components of CHADS2 score (CHF, hypertension, Age&gt;75, diabetes and stroke/TIA) were identified using ICD 9 codes. χ2 tests performed for prevalence of AF in patients with or without these cancers stratified by CHADS2 score. Binary logistic regression was used to analyze individual components of CHADS2 score. Results AF and stroke/TIA were significantly higher among 4CA than non-4CA group (18.7% vs 12.0%, P&lt;0.001 and 5.4% vs 4.8%, P&lt;0.001 respectively). AF prevalence increased with CHADS2 and was significantly higher in 4CA group with CHADS2 score 0 to 4 (Table 1 and Figure 1). Logistic regression for the outcome of AF showed “Age &gt;75” OR (3.0), CHF (2.8), CVA (1.2), HTN (1.3) and DM (1.1). Conclusion This is the first study using a national database of USA patients to estimate prevalence of AF in cancer patients compared to non-cancer patients and reaffirms the higher burden of AF in cancer patients. Prevalence of both AF and stroke were greater in cancer patients when stratified by CHADS2 score. This may indicate not just an increased risk of AF but an increased risk of stroke/TIA for the same CHADS2 score. Stroke incidence was also higher in the 4CA group (5.4% vs. 4.8% P&lt;0.001). Cancer patients with CHADS2 score &gt;1 may benefit from screening with loop recorder to identify previously undetected AF and initiate anticoagulation therapy. Prospective longitudinal studies are needed to validate this retrospective study. Funding Acknowledgement Type of funding source: None