Contemporary management of patients with atrial fibrillation in the Netherlands and Belgium: a report from the EORP-AF long-term general registry.

BACKGROUND: Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. METHODS: We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1­year follow-up data were gathered. RESULTS: At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). CONCLUSIONS: Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.

Performance and clinical comparison between left ventricular quadripolar and bipolar leads in cardiac resynchronization therapy: Observational research.

AIM: To evaluate Attain Performa (Medtronic, Dublin, Ireland) quadripolar lead performance in clinical practice and, secondarily, to compare its long term clinical outcomes vs bipolar leads for left ventricular (LV) pacing. METHODS AND RESULTS: We retrospectively analyzed clinical, procedural and follow-up data of 215 patients implanted with a quadripolar lead. One hundred and twenty one patients implanted with bipolar lead were selected to compare long-term clinical outcomes. The quadripolar lead was implanted in the target vein in 196 patients (91%) without acute dislodgements. In 50% of patients the chosen final pacing configuration at implant would not have been available with bipolar leads. A dedicated quadripolar pacing vector was chosen more frequently when the LV tip location was apical than otherwise (65.6% vs 42.7%, p=0.003). After a median follow-up of 14 months, the LV pacing threshold was less than 2.5V at 0.4ms in 98 patients (90%) with a safety margin between phrenic nerve and LV pacing threshold >3V in 97 patients (89%). We observed a slight trend toward a lower risk of heart failure worsening and a lower incidence of ventricular arrhythmias and pulmonary congestion in patients implanted with quadripolar leads compared with the control group. CONCLUSION: Quadripolar leads improve the management of phrenic nerve stimulation at no trade-off with pacing threshold and lead stability. Quadripolar leads seems to be associated with a lower incidence of VT/VF and pulmonary congestion, when compared with bipolar leads, but further investigations are necessary to confirm that this positive effect is associated with better LV reverse remodeling.

Cardiac resynchronization therapy: a comparison among left ventricular bipolar, quadripolar and active fixation leads.

We evaluated the performance of 3 different left ventricular leads (LV) for resynchronization therapy: bipolar (BL), quadripolar (QL) and active fixation leads (AFL). We enrolled 290 consecutive CRTD candidates implanted with BL (n = 136) or QL (n = 97) or AFL (n = 57). Over a minimum 10 months follow-up, we assessed: (a) composite technical endpoint (TE) (phrenic nerve stimulation at 8 V@0.4 ms, safety margin between myocardial and phrenic threshold <2V, LV dislodgement and failure to achieve the target pacing site), (b) composite clinical endpoint (CE) (death, hospitalization for heart failure, heart transplantation, lead extraction for infection), (c) reverse remodeling (RR) (reduction of end systolic volume >15%). Baseline characteristics of the 3 groups were similar. At follow-up the incidence of TE was 36.3%, 14.3% and 19.9% in BL, AFL and QL, respectively (p < 0.01). Moreover, the incidence of RR was 56%, 64% and 68% in BL, AFL and QL respectively (p = 0.02). There were no significant differences in CE (p = 0.380). On a multivariable analysis, "non-BL leads" was the single predictor of an improved clinical outcome. QL and AFL are superior to conventional BL by enhancing pacing of the target site: AFL through prevention of lead dislodgement while QL through improved management of phrenic nerve stimulation.

Arterial hypertension in patients with atrial fibrillation in Europe: A report from the EURObservational Research Programme pilot survey on atrial fibrillation.

BACKGROUND: Hypertension (HTN) is the most prevalent co-morbidity among atrial fibrillation (AF) patients; the relationship between the two is bidirectional, with an incremental effect on adverse outcomes. PURPOSE: To study clinical features, treatment patterns and 1year outcomes amongst AF patients with HTN in the EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry, a prospective multi-national survey conducted by the European Society of Cardiology in 9 European countries. METHODS: Of 3119 enrolled AF patients, 2194 were diagnosed with HTN (AF-HTN) and 909 were normotensive (AF-NT) (16 patients had unknown HTN status). We compared baseline clinical features, management strategy and 1-year outcomes in terms of all-cause death, cardiovascular (CV) death, and any thrombosis-related event (TE: stroke, transient ischemic attack, acute coronary syndrome, coronary intervention, cardiac arrest, peripheral/pulmonary embolism) in AF-HTN vs AF-NT patients. RESULTS: The AF-HTN patients had more prevalent CV risk factors and comorbidities (median CHA2DS2-VASc score (IQR) 4 (3, 5) in AF-HTN, versus 2 (1, 3) in AF-NT; p<0.01). Crude rate of all-cause death and any TE event was higher in AF-HTN (194 (11.2%) versus 60 (8.2%), p=0.02). Kaplan-Meier analysis curves for death by hypertensive status showed no significant differences between the subgroups (log rank test, p=0.22). On logistic regression analysis, HTN did not emerge as an independent risk factor for outcomes (OR 1.08, 95% CI 0.76-1.54). CONCLUSION: AF-HTN patients have a higher prevalence of comorbidities and this conferred a higher risk for a composite endpoint of all-cause death and thromboembolic events. In this cohort HTN did not independently predict all-cause mortality at 1-year.

Use of antihistamines and risk of ventricular tachyarrhythmia: a nested case-control study in five European countries from the ARITMO project.

PURPOSE: After regulatory restrictions for terfenadine and astemizole in '90s, only scarce evidence on proarrhythmic potential of antihistamines has been published. We evaluate the risk of ventricular tachyarrhythmia (VA) related to the use of individual antihistamines. METHODS: A matched case-control study nested in a cohort of new users of antihistamines was conducted within the EU-funded ARITMO project. Data on 1997-2010 were retrieved from seven healthcare databases: AARHUS (Denmark), GEPARD (Germany), HSD and ERD (Italy), PHARMO and IPCI (Netherlands) and THIN (UK). Cases of VA were selected and up to 100 controls were matched to each case. The odds ratio (OR) of current use for individual antihistamines (AHs) was estimated using conditional logistic regression. RESULTS: For agents largely used to prevent allergic symptoms, such as cetirizine, levocetirizine, loratadine, desloratadine and fexofenadine, we found no VA risk. A statistically significant, increased risk of VA was found only for current use of cyclizine in the pooled analysis (ORadj, 5.3; 3.6-7.6) and in THIN (ORadj, 5.3; 95% CI, 3.7-7.6), for dimetindene in GEPARD (ORadj, 3.9; 1.1-14.7) and for ebastine in GEPARD (ORadj, 3.3; 1.1-10.8) and PHARMO (ORadj, 4.6; 1.3-16.2). CONCLUSIONS: The risk of VA associated with a few specific antihistamines could be ascribable to heterogeneity in pattern of use or in receptor binding profile.

The cost of atrial fibrillation in Italy: a five-year analysis of healthcare expenditure in the general population. From the Italian Survey of Atrial Fibrillation Management (ISAF) study.

OBJECTIVE: Atrial fibrillation (AF) is a relevant item of expenditure for the National Healthcare systems. The aim of the study was to estimate the annual costs of AF in Italy. PATIENTS AND METHODS: The Italian Survey of Atrial Fibrillation Management Study enrolled 6.036 patients with AF among 295.906 subjects representative of the Italian population. Data were collected by 233 General Practitioners (GPs) distributed across Italy. Quantities of resources used during the 5 years preceding the ISAF screening were inferred from the survey data and multiplied by the current Italian unit costs of 2015 in order to estimate the mean per patient annual cumulative cost of AF. Patients were subdivided on the basis of the number of hospitalizations, invasive/non-invasive diagnostic tests and invasive therapeutic procedures in 3 different clinical subsets: "low cost", " medium cost" and "high cost clinical scenario". RESULTS: The estimated mean costs per patient per year were 613 €, 891 € and 1213 € for the "Low cost", "Medium cost" and "High Cost Clinical Scenario" respectively. Hospitalizations and inpatient interventional procedures accounted for more than 80% of the cumulative annual costs. The mean annual costs among patients pursuing "Rhythm control" strategy was 956 €. CONCLUSIONS: In Italy, the estimated costs of AF per patient per year are lower than those reported in other developed countries and vary widely related to the different characteristics of AF patients. Hospitalizations and interventional procedures are the main drivers of costs. The mean annual cost of AF is mainly influenced by the duration of the period of observation and the patients' characteristics. Measures to reduce hospitalizations are needed.

A tailored treatment strategy: a modern approach for stroke prevention in patients with atrial fibrillation.

The main priority in atrial fibrillation (AF) management is stroke prevention, following which decisions about rate or rhythm control are focused on the patient, being primarily for management of symptoms. Given that AF is commonly associated with various comorbidities, risk factors such as hypertension, heart failure, diabetes mellitus and sleep apnoea should be actively looked for and managed in a holistic approach to AF management. The objective of this review is to provide an overview of modern AF stroke prevention with a focus on tailored treatment strategies. Biomarkers and genetic factors have been proposed to help identify 'high-risk' patients to be targeted for oral anticoagulation, but ultimately their use must be balanced against that of more simple and practical considerations for everyday use. Current guidelines have directed focus on initial identification of 'truly low-risk' patients with AF, that is those patients with a CHA2 DS2 -VASc [congestive heart failure, hypertension, age ≥75 years (two points), diabetes mellitus, stroke (two points), vascular disease, age 65-74 years, sex category] score of 0 (male) or 1 (female), who do not need any antithrombotic therapy. Subsequently, patients with ≥1 stroke risk factors can be offered effective stroke prevention, that is oral anticoagulation. The SAMe-TT2 R2 [sex female, age <60 years, medical history (>2 comorbidities), treatment (interacting drugs), tobacco use (two points), race non-Caucasian (two points)] score can help physicians make informed decisions on those patients likely to do well on warfarin (SAMe-TT2 R2 score 0-2) or those who are likely to have a poor time in therapeutic range (SAMe-TT2 R2 score >2). A clinically focused tailored approach to assessment and stroke prevention in AF with the use of the CHA2 DS2 VASc, HAS-BLED [hypertension, abnormal renal/liver function (one or two points), stroke, bleeding history or predisposition, labile international normalized ratio, elderly (>65 years) drugs/alcohol concomitantly (one or two points)] and SAMeTT2 R2 scores to evaluate stroke risk, bleeding risk and likelihood of successful warfarin therapy, respectively, is discussed.

Tailored treatment strategies: a new approach for modern management of atrial fibrillation.

Atrial fibrillation (AF) is not benign. Cardiovascular diseases and risk factors differ importantly amongst patients. Careful phenotyping with the aim to start tailored therapy may improve outcome and quality of life. Furthermore, structural remodelling plays an important role in initiation and progression of AF. Therapies that interfere in the remodelling processes are promising because they may modify the atrial substrate. However, success is still limited probably due to variations in the underlying substrate in individual patients. The most favourable effects of lifestyle changes on success of rhythm control have been demonstrated in obese patients with AF. Differences in genotype may also play an important role. Common gene variants have been associated with recurrence of AF after electrical cardioversion, antiarrhythmic drug therapy and catheter ablation. Therefore, both phenotyping and genotyping may become useful for patient selection in the future. Beside the choice of rate or rhythm control, and type of rhythm control, prevention of complications associated with AF may also differ depending on genotype and phenotype. Efficacy of stroke prevention has been well established, but bleeding remains a clinically relevant problem. Risk stratification is still cumbersome, especially in low-risk patients and in those with a high bleeding risk. The decision whether to start anticoagulation (and if so which type of anticoagulant) or, alternatively, to implant an occlusion device of the left atrial appendage may also be improved by genotyping and phenotyping. In this review, we will summarize new insights into the roles of phenotype and genotype in generating more tailored treatment strategies in patients with AF and discuss several patient-tailored treatment options.

AF burden is important - fact or fiction?

Asymptomatic atrial fibrillation (AF) is common and in view of its prognostic impact (the same as of clinically overt AF) knowledge of the overall AF burden (defined as the amount of time spent in AF) appears to be important, both for scientific and clinical reasons. Data collected on more than 12,000 patients indicate that cardiac implantable electrical devices (CIEDs) are validated tools for measuring AF burden and that AF burden is associated with an increased risk of stroke. A maximum daily AF burden of ≥ 1 h carries important negative prognostic implications and may be a clinically relevant parameter for improving risk stratification for stroke. Decision-making should primarily consider the context in which asymptomatic, subclinical arrhythmias are detected (i.e. primary or secondary prevention of stroke and systemic embolism) and the risk profile of every individual patient with regard to thromboembolic and haemorrhagic risk, as well as patient preferences and values. Continuous monitoring using CIEDs with extensive data storage capabilities allow in-depth study of the temporal relationship between AF and ischaemic stroke. The relationships between AF and stroke are complex. AF is certainly a risk factor for cardioembolic stroke, with a cause-effect relationship between the arrhythmia and a thromboembolic event, the latter being related to atrial thrombi. However, AF can also be a simple 'marker of risk', with a non-causal association between the arrhythmia and stroke, the latter being possibly related to atheroemboli from the aorta, the carotid arteries or from other sources.

Changes in exercise capacity induced by heart transplantation: prognostic and therapeutic implications.

Survival and exercise performance are key targets of heart transplantation (HT). We designed this study to help in identifying (1) patients with chronic heart failure (CHF) at risk of poor exercise capacity after HT and (2) HT recipients presenting risk factors modifiable with exercise showing a potential impact on outcome. We enrolled 49 HT recipients (age 52 ± 12 years, 84% males) who underwent a cardiopulmonary exercise test before (9 ± 6 months) and after (20 ± 14 months) HT. In the CHF phase, lower peak oxygen consumption (VO(2) ) (odds ratio 0.69, P=0.017) independently predicted peak VO(2) improvement after HT. In the post-HT phase, body mass index (BMI) [adjusted hazard ratio (HR) 1.16, P=0.034] and VE (ventilation)/VCO(2) (carbon dioxide production) slope (adjusted HR 1.07, P=0.031) independently predicted mortality. In conclusion, CHF patients with only a moderate impairment of peak VO(2) are at a risk of failing to achieve a significant improvement of exercise performance after HT. In the post-HT phase, a BMI≥28 and/or a VE/VCO(2) slope ≥47 represent risk factors for death, which are potentially modifiable with exercise. Prospective randomized studies are needed to analyze the effects of training on functional capacity and outcome in the different subsets of HT recipients.

Expenditure and value for money: the challenge of implantable cardioverter defibrillators.

Many technology-driven interventions entail considerable financial cost, raising affordability issues. The implantable cardioverter defibrillator (ICD) is a case of an effective primary prevention intervention with high initial costs that is capable of delivering long-term population benefits. At first glance, such interventions may provoke diffidence, if not active resistance, due to the financial burdens which inevitably accompany their widespread adoption. In this article, we review the available economic tools that can help address the ICD cost issue. We think awareness of such knowledge may facilitate dialogues between physicians, administrators and policymakers, and help foster rational decision-making.

Electrical cardioversion for persistent atrial fibrillation or atrial flutter in clinical practice: predictors of long-term outcome.

Despite the results of Atrial Fibrillation Follow-up Investigation of Rhythm Management and Rate Control versus Electrical Cardioversion for Persistent Atrial Fibrillation trials, which favour a general shift in atrial fibrillation (AF) therapeutic approach towards control of ventricular rate, a strategy based on restoration of sinus rhythm could still play a role in selected patients at lower risk of AF recurrence. We explored possible predictors of relapses after external electrical cardioversion among patients with persistent AF or atrial flutter (AFL). We analysed the clinical characteristics and conventional echocardiographic parameters of patients with persistent AF/AFL enrolled in an institutional electrical cardioversion programme. Among 242 patients (AF/AFL, 195/47; mean age 62+/-13 years), sinus rhythm was restored in 215 (89%) and maintained in 73 (34%) at a follow-up of 930 days (median). No baseline clinical/echocardiographic variables predicted acute efficacy of cardioversion at logistic regression analysis. However, two variables predicted long-term AF/AFL recurrence among patients with successful cardioversion at multivariate Cox's proportional hazards analysis: (i) duration of arrhythmia>or=1 year (HR, 2.07; 95% CI, 1.29-3.33) and (ii) presence of previous cardioversion (HR, 1.67; 95% CI, 1.17-2.38). These variables also presented high-positive predictive values (72% and 80% respectively). Whereas the high acute efficacy of electrical cardioversion (approximately 90%) does not appear to be predictable, two simple clinical variables could help identify patients at higher risk of long-term AF/AFL recurrence after successful electrical cardioversion. We think there could be a case for initially attempting external electrical cardioversion to patients who have had AF/AFL for <1 year. In such patients, the chance of long-term success appears to be relatively high.

Wide spectrum of presentation and variable outcomes of isolated left ventricular non-compaction.

OBJECTIVES: To investigate diagnostic routes, echocardiographic substrates, outcomes and prognostic factors in patients with isolated ventricular non-compaction (IVNC) identified by echocardiographic laboratories with referral from specialists and primary care physicians. PATIENTS AND DESIGN: Since 1991, all patients with suspected IVNC were flagged and followed up on dedicated databases. Patients were divided into symptom-based and non-symptom-based diagnostic subgroups. RESULTS: 65 eligible patients were followed up for 6-193 months (mean 46 (SD 44). In 53 (82%) patients, IVNC was associated with variable degrees of left ventricular (LV) dilatation and hypokinesia, and in the remaining 12 (18%) LV volumes were normal. Diagnosis was symptom based in 48 (74%) and non-symptom based in 17 (26%) (familial referral in 10). The non-symptom-based subgroup was characterised by younger age, lower prevalence of ECG abnormalities, better systolic function and lower left atrial size, whereas the extent of non-compaction was not different. No major cardiovascular events occurred in the non-symptom-based group, whereas 15 of 48 (31%) symptomatically diagnosed patients experienced cardiovascular death or heart transplantation (p = 0.01, Kaplan-Meier analysis). Independent predictors of cardiovascular death or heart transplantation were New York Heart Association class III-IV, sustained ventricular arrhythmias and left atrial size. CONCLUSIONS: IVNC is associated with a broad spectrum of clinical and pathophysiological findings, and the overall natural history and prognosis may be better than previously thought. Adult patients with incidental or familial discovery of IVNC have an encouraging outlook, whereas those who have symptoms of heart failure, a history of sustained ventricular tachycardia or an enlarged left atrium have an unstable course and more severe prognosis.

Amyloid deposition as a cause of atrial remodelling in persistent valvular atrial fibrillation.

AIM: The spectrum of histological alterations, namely atrial amyloidosis, in the right and left atria of patients with chronic persistent atrial fibrillation (AF) and rheumatic heart disease is not completely known. METHODS AND RESULTS: One hundred and twenty-eight atrial appendages (66 left and 62 right), obtained from 72 patients with rheumatic valve disease and chronic AF undergoing cardiac surgery for valve replacement or repair and AF treatment were histologically evaluated for the presence of amyloid deposits. One hundred and four specimens of left and right auricles from 52 patients in sinus rhythm with severe chronic heart failure undergoing heart transplant were also analyzed (controls). Amyloid was found in 33 (46%) valvular patients with chronic persistent AF and in 6 (12%) controls. Amyloid was related to the presence and duration of AF, was more frequently found in left atrial samples and was independent of age. On stepwise logistic regression analysis, AF duration and female gender were independently related to amyloid deposition. CONCLUSIONS: Patients with long-standing AF and rheumatic heart disease have a very high prevalence of atrial amyloidosis. Amyloid deposition is more frequent in left than in right atrial appendage and correlates with AF duration and female gender. Amyloid deposition could constitute an additional histological feature in the structural remodeling of atria during long-standing AF, at least in rheumatic valve disease. Persistence of AF might play a pivotal role in promoting amyloid deposition.