Michał Mazurek

Regional Differences in Antithrombotic Treatment for Atrial Fibrillation: Insights from the GLORIA-AF Phase II Registry

Introduction  Although guideline-adherent antithrombotic therapy (ATT) for stroke prevention in atrial fibrillation (AF) is associated with lower mortality and thromboembolism, ATT uptake shows geographic variation worldwide. We aimed to assess thromboembolic risk and baseline ATT by geographic region and identify factors associated with prescription of ATT in a large, truly global registry of patients with recently diagnosed AF. Methods and Results  Our analysis comprises 15,092 patients newly diagnosed with non-valvular AF at risk for stroke, enrolled in Phase II of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF). Global oral anticoagulation (OAC) use was 79.9%, being highest in Europe (90.1%), followed by Africa/Middle East (87.4%) and Latin America (85.3%), North America (78.3%) and Asia (55.2%). Among OAC users, vitamin K antagonists (VKAs) have been replaced by non-VKA OACs (NOACs) as the more prevalent OAC option in all regions, with highest use in North America (66.5%) and lowest in Asia (50.2%). In Asia, OAC was 80.4% in community hospitals but only 49.8% in university hospitals and 42.6% in specialist offices, and varied from 21.0% in China to 89.7% in Japan (NOACs at 5.8% in China and 83.3% in Japan). Globally, 76.5% of low-risk patients were prescribed ATT (46.1% OAC), whereas 17.7% high-risk patients were not anticoagulated (Europe 8.8%; North America 18.9%; Asia 42.4%). Conclusion  Substantial inter- and intra-regional differences in ATT for stroke prevention in AF are evident in this global registry. While guideline-adherent ATT can be further improved, NOACs are the main contributor to high OAC use worldwide.

Balancing thromboembolic and bleeding risk with non-vitamin K antagonist oral anticoagulants (NOACs): A systematic review and meta-analysis on gender differences

Graphical abstract Summary of evidence obtained from systematic review and meta‐analysis of NOACs trials. Legend: AF = atrial fibrillation; NOACs = non‐vitamin K antagonists oral anticoagulants; RCTs = randomized clinical trials. Figure. No Caption available. Abstract Sex and gender differences have been reported in atrial fibrillation (AF), especially in relation to differences in thromboembolic and bleeding risks. More recently, pharmacological treatments have changed following the introduction of non‐vitamin K antagonist oral anticoagulants (NOACs) progressively replacing vitamin K antagonists (VKAs). The aims of this systematic review are to summarize the available evidence on NOACs and the relationship to major adverse outcomes according to sex. Moreover, we performed a meta‐analysis of data from the phase III clinical trials investigating the sex effect on stroke/systemic embolic events (SEE) and major bleeding. Our literature review found small differences in NOACs efficacy and safety between male and female patients, even if so far available literature is limited to post‐hoc ancillary analyses from randomized trials and one cohort study. Meta‐analysis from NOAC trials found a differential effect of NOACs, with male patients being more protected from stroke/SEE and female patients more protected from major bleeding events. Further data are needed to fully elucidate sex differences in AF patients treated with NOACs.

Guideline-Adherent Antithrombotic Treatment Improves Outcomes in Patients With Atrial Fibrillation: Insights From the Community-Based Darlington Atrial Fibrillation Registry

Objective: To assess the influence of guideline‐adherent vs nonadherent antithrombotic treatment (ATT) on stroke and mortality rates in an atrial fibrillation (AF) primary care population. Patients and Methods: We used the Darlington Registry cohort, which included 105,000 patients from March 31, 2012, through March 31, 2013. Guideline adherence in ATT was assessed against 2014 National Institute for Health and Care Excellence guidelines, which recommend oral anticoagulation for stroke prevention as a default management unless a truly low risk of stroke (CHA2DS2‐VASc=0 in men and 1 in women) is evident. Results: Of 2259 patients with AF (2.15%), 36.1% were undertreated, 50.8% were guideline adherent, and 13.1% were overtreated. Oral anticoagulation was declined by 5.0% and contraindicated in 8.3%. Of 67 incident strokes (3.0%), 66 (98.5%) occurred in high‐risk patients (CHA2DS2‐VASc ≥2). For the high‐risk cohort, 1‐year stroke rates were 4.5% (95% CI, 3.2%‐6.3%) for undertreatment, 1.9% (95% CI, 1.2%‐2.9%) for guideline adherence, and 7.2% (95% CI, 4.4%‐11.6%) for overtreatment; corresponding mortality rates were 16.1% (95% CI, 13.6%‐19.0%), 8.0% (95% CI, 6.5%‐9.8%), and 8.2% (95% CI, 5.2%‐12.7%), respectively. On multivariable analysis, both undertreatment and overtreatment of high‐risk patients were associated with significant increases in stroke rates (odds ratio [OR]=2.32; 95% CI, 1.30‐3.14; P=.005 and OR=2.28; 95% CI, 1.12‐4.63; P=.02, respectively). Undertreatment was also associated with a significant increase in all‐cause mortality (OR=1.59; 95% CI, 1.14‐2.21; P=.006). Conclusion: Only half of all eligible patients with AF are prescribed oral anticoagulation in accordance with guideline recommendations. Guideline‐adherent ATT significantly reduces the risk of stroke and improves survival.

Polish and European management strategies in patients with atrial fibrillation. Data from the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase (EORP-AF Pilot).

INTRODUCTION Despite continued efforts of the European Society of Cardiology (ESC) to unify management of patients with atrial fibrillation (AF) across Europe, interregional differences in guideline adherence are likely. OBJECTIVES The aim of the study was to compare treatment strategies depending on baseline characteristics of AF patients between Poland and other members of the European Union (EU). PATIENTS AND METHODS We analyzed the baseline data and treatment strategies in participants of the ESC registry: the EURObservational Research Programme-Atrial Fibrillation General Registry Pilot Phase. A total of 3119 consecutive patients with AF diagnosed within the last year were included in 67 centers from 9 countries, including 419 patients enrolled in 15 Polish centers. RESULTS A rhythm control strategy was more frequent in Poland than in other EU countries (20.8% vs 11.9%; P <0.0001). Catheter ablation for AF was also used more frequently in Polish cardiology wards (13.9% vs 8.3%; P = 0.0017), while amiodarone at discharge was used less frequently (12.0% vs 22.7%; P <0.0001). In-hospital use of vitamin K antagonists (VKAs) and non-VKA anticoagulants was less frequent in Polish patients with a CHA2DS2-VASc score of 2 or higher than in patients from other EU countries (61.1% vs 79.0%; P <0.0001), but overall anticoagulation rates at discharge were similar to those in other countries (83.3% vs 82.6%). CONCLUSIONS A rhythm control-oriented strategy in patients with AF with the use of ablation in cardiology wards is more frequent in Poland than in other EU countries. Similar to other EU countries, compliance with the ESC guidelines regarding anticoagulation in AF patients is suboptimal in Poland. Undertreatment was observed in a significant proportion of patients at high risk of stroke, while a large group of low-risk patients are overtreated. Differences between the types of recruiting centers in Poland and other EU countries might have influenced the results.

Efficacy of cardiac resynchronisation therapy in the treatment of end-stage inotrope-dependent heart failure patients.

BACKGROUND AND AIM Currently, cardiac resynchronisation therapy (CRT) is recommended only for New York Heart Association (NYHA) class IV ambulatory patients. However, some recent reports have suggested that CRT could also be beneficial for end-stage inotrope-dependent heart failure (HF) NYHA class IV patients. In this report, we summarise the results of CRT implantation in a group of 11 HF inotrope-dependent patients who were not candidates for urgent orthotopic heart transplantation (OHT). METHODS AND RESULTS Between August 2006 and June 2011, 11 end-stage inotrope-dependent HF patients with wide QRS complex, ineligible for urgent OHT, were implanted with CRT in the Silesian Centre for Heart Diseases in Zabrze. Dependence on inotropic therapy was defined as an inability to stop the infusion of the drug without the occurrence of hypotension, oligooranuria and/or hypoxaemia. All patients were successfully implanted with CRT and subsequently weaned from inotropes in a median time of two (1-17) days. Mean QRS duration shortened from 190 ± 34 ms at baseline to 142 ± 25 ms (p < 0.001) after the procedure. Average left ventricular ejection fraction increased from 19 ± 4% to 25 ± 4% (p < 0.001). All patients were discharged from hospital. Median hospital stay after the procedure was ten (5-56) days. During the median follow-upof 1,212 (182-2,048) days, four patients died (one due to arrhythmic storm, three others due to progressive pump failure). During that period, 57 adequate device interventions occurred in three patients, including 52 therapies in one fatal case. CONCLUSIONS CRT can be an alternative for end-stage inotrope-dependent HF patients with wide QRS who are ineligible for urgent heart transplantation.

Can we rely on machines? Device-detected atrial high rates correspond well with atrial arrhythmias in cardiac resynchronization recipients

AIMS The aim of the study was to verify in what proportion of patients, device-detected atrial high rate (AHR) episodes are indeed atrial arrhythmias (AAs). We investigated also the reasons for inappropriate arrhythmia classification and assessed if patients with misdiagnosed arrhythmias have distinct characteristics that would help to identify them. METHODS AND RESULTS The study population consisted of 304 consecutive patients implanted with cardiac resynchronization therapy defibrillators (CRT-Ds) and subsequently monitored via remote monitoring for a median follow-up (FU) of 30.5 months. Intracardiac electrograms of every recorded AHR episode were assessed and classified (AA vs. no AA) by two experienced cardiologists. During FU, 14 386 episodes of AHR were recorded and classified in 176 (57.9%) patients. In 89.2% of them, these episodes were true AA (94% atrial fibrillation, 62% de novo). The reasons for AHR misdiagnosis were atrial far-field signals (89.5%) and noise (10.5%). The mean per cent of day spent in AHR (54.9 vs. 5.86%; P < 0.001) and the occurrence of periods with low CRT pacing (82.8 vs. 55%; P = 0.003) were significantly higher in AA subjects than in those with misdiagnosed AHR. Episode duration of properly detected AHRs was longer than that of misdiagnosed AHRs. Higher per cent of time spent in AHR was an independent marker of appropriate arrhythmia detection [adjusted hazard ratio (HR) 1.04; P = 0.023]. CONCLUSION Nearly two-thirds of CRT-D patients had AHR episodes within 2.5 years after implantation. Almost 90% of AHRs were indeed AA. Misdetections were caused by far-field sensing or noise. A two-step diagnostic algorithm (>9% of time spent in AHRs and episode duration >36 s) allowed for proper detection of AA with a high hit-rate and specificity.

Secondary Versus Primary Stroke Prevention in Atrial Fibrillation: Insights From the Darlington Atrial Fibrillation Registry

Background and Purpose— Although patients with atrial fibrillation (AF) who experienced an acute stroke are at high risk for recurrence, many patients are untreated or treated suboptimally for stroke prevention. The objective of this study is to compare clinical outcomes of AF patients with versus without previous stroke in relation to guideline-adherent antithrombotic treatment in a contemporary primary care population. Methods— Community cohort of 105 000 patients from 11 general practices in Darlington, England, was used to assess AF stroke prevention strategies against 2014 National Institute for Health and Care Excellence guidelines. Results— Overall, 2259 (2.15%) patients with AF were identified, of which 18.9% constituted a secondary prevention cohort. For secondary prevention, antithrombotic treatment was guideline adherent in 56.3%, 18.9% were overtreated, and 24.8% undertreated; corresponding proportions for primary prevention were 49.5%, 11.7%, and 38.8%, respectively. One-year stroke rates were 8.6% and 1.6% for secondary and primary prevention, respectively (P<0.001); corresponding all-cause mortality rates were 9.8% and 9.4%, respectively (P=0.79). On multivariable analysis, lack of antithrombotic treatment guideline adherence was associated with increased stroke risk for primary prevention (odds ratio, 2.95; 95% confidence interval, 1.26–6.90; P=0.013 for undertreatment); for secondary prevention, lack of guideline adherence was associated with increased risk of recurrent stroke (odds ratio, 2.80; 95% confidence interval, 1.25–6.27; P=0.012 for overtreatment) and all-cause death (odds ratio, 2.75; 95% confidence interval, 1.33–5.69; P=0.006 for undertreatment). Conclusions— Only approximately half of eligible patients with AF are prescribed oral anticoagulation in line with guidelines. Guideline-adherent antithrombotic treatment significantly reduces the risk of stroke among primary prevention patients and both risk of recurrent stroke and death in patients with previous stroke.

Device-related infective endocarditis in cardiac resynchronization therapy recipients — Single center registry with over 2500 person-years follow up

AIM To assess incidence, predisposing factors and outcomes of cardiac device-related infective endocarditis (CDRIE) in patients undergoing cardiac resynchronization therapy (CRT). METHODS AND RESULTS High-volume, single-center cardiology database was screened to identify all CDRIE cases, based on modified Duke criteria, amongst 765 consecutive CRT implantations between 2002 and 2015 (70.8% de novo implantations, 13.7% and 15.5% up-grades from pacemaker and implantable cardioverter–defibrillator [ICD], respectively). During the median follow-up (FU) of 1207 days (range: 256–2664) overall 38 CDRIE (4.97%) cases were identified (incidence: 15/1000 person-years). Multivariate Cox regression model, incorporating significant baseline differences as covariates (model 1), demonstrated that both up-grade from ICD to CRT and higher baseline NYHA class were independently associated with increased risk of CDRIE (adjusted HR 4.29, 95%CI 1.93–9.57; and HR 2.43, 95%CI 1.32–4.49, respectively). In the second model (including all differences with P < 0.2) up-grade from ICD (HR 4.36, 95%CI 1.96–9.69), higher NYHA class (HR 2.04, 95%CI 1.11–3.75), hypertrophic cardiomyopathy (HR 5.85, 95% CI 1.46–23.52), lower baseline hemoglobin level (HR 0.68, 95%CI 0.50–0.94) and chronic obstructive pulmonary disease (HR 2.46, 95%CI 1.05–5.77) were all independently associated with higher risk of CDRIE. All-cause mortality in patients with CDRIE was significantly higher than in subjects without infective complications (68.4% vs. 33.7%, P < 0.001), and 50% of patients with CDRIE died during index hospitalization. CONCLUSIONS The prevalence of CDRIE in CRT recipients is almost 5% within 3.5 years post implantation. Up-grade from ICD and high baseline NYHA class flag up patients at high-risk of CDRIE. CRT-related infective complications are associated with very poor prognosis.

Do we need to monitor the percentage of biventricular pacing day by day

BACKGROUND Incidence and clinical significance of transient, daily fluctuations of biventricular pacing percentage (CRT%) remain unknown. We assessed the value of daily remote monitoring in identifying prognostically critical burden of low CRT%. METHODS AND RESULTS Prospective, single-centre registry encompassed 304 consecutive heart failure patients with cardiac resynchronization therapy defibrillators (CRT-D). Patients with 24-h episodes of CRT% loss<95% were assigned to quartiles depending on cumulative time spent in low CRT%: quartile 1 (1-8days), 2 (9-20days), 3 (21-60days) and quartile 4 (>60days). During median follow-up of 35months 51,826 transmissions were analysed, including 15,029 in 208 (68.4%) patients with episodes of low CRT%. Overall, mean CRT%≥95% vs. <95% resulted in a 4-fold lower mortality (17.3 vs. 68.2%; p<0.001). Fifty-four percent of patients experienced episodes of CRT% loss, despite 85.6% having mean CRT%≥95%. Mortality was lowest in quartile 1 (7.7%), while longer periods of CRT% loss resulted in significantly higher death rates (25.0 vs. 34.6 vs. 57.7%; quartiles 2-4 respectively, p<0.001), despite mean CRT% still being ≥95% in quartiles 1-3. Cumulative low CRT% burden was the independent risk factor for death (HR 1.013; 95% CI 1.006-1.021; p<0.001). Mortality rose by 1.3 and 49% with every additional day and quartile of CRT% loss, respectively. CONCLUSIONS Daily remote monitoring allows one to detect 24-h episodes of CRT% loss<95% in over two-thirds of CRT-D recipients during median observation of 3years. Cumulative low CRT% burden (in days) independently predicts mortality before mean CRT% drop.

Atrial fibrillation in cardiac resynchronization recipients with and without prior arrhythmic history. How much of arrhythmia is too much

BACKGROUND The aim of the study was to assess long-term incidence of atrial fibrillation (AF) in cardiac resynchronization (CRT) recipients with and without prior arrhythmic history, factors predisposing to arrhythmia, as well as to evaluate the prognostic power of cumulative arrhythmia burden, duration of the longest episode and the number of episodes. METHODS Device-collected data on AF episodes during 24 months in 96 participants of a randomized CRT-trial were analyzed (15% in NYHA class IV, sinus rhythm, median left ventricular ejection fraction 24% and QRS 169 ms). Blindly adjudicated major adverse cardiac events (MACE) and any-cause death were censoring variables. RESULTS Two-year incidence of AF was 70%, including 66% of patients without previous AF history. No baseline characteristics distinguished those who developed new onset AF. Percent of time spent in AF, but not number of episodes predicted mortality (adjusted hazard ratio [HR] 1.05 ± 95% confidence interval CI 1.01-1.10) and MACE incidence (HR 1.03 ± 1.01-1.07; p = 0.03). Duration of the longest episode also predicted mortality (HR 1.06 ± 1.01-1.12; both p = 0.03). Prognostic impact of AF load was marked only in patients with slower ventricular response (< 98/min), but was independent from CHADS2 scores, pacing burden, or prior atrioventricular nodal ablation. CONCLUSIONS Seven out of 10 CRT-patients had AF within 2 years, including two-thirds of subjects without arrhythmic history. No baseline features distinguished those who developed new onset AF. Arrhythmia burden and duration of the longest episode, but not number of episodes influenced outcomes in CRT-patients, irrespectively from pacing burden or prior atrioventricular node ablation.