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Aims ST-depression and T-wave inversion are frequently present on the post-resuscitation electrocardiogram (ECG). However, the prognostic value of ischaemic ECG patterns is unknown. Methods and results In this post-hoc subgroup analysis of the Coronary Angiography after Cardiac arrest (COACT) trial, the first in-hospital post-resuscitation ECG in out-of-hospital cardiac arrest patients with a shockable rhythm was analysed for ischaemic ECG patterns. Ischaemia was defined as ST-depression of ≥0.1 mV, T-wave inversion in ≥2 contiguous leads, or both. The primary endpoint was 90-day survival. Secondary endpoints were rate of acute unstable lesions, levels of serum troponin-T, and left ventricular function. Of the 510 out-of-hospital cardiac arrest patients, 340 (66.7%) patients had ischaemic ECG patterns. Patients with ischaemic ECG patterns had a worse 90-day survival compared with those without [hazard ratio 1.51; 95% confidence interval (CI) 1.08–2.12; P = 0.02]. A higher sum of ST-depression was associated with lower survival (log-rank = 0.01). The rate of acute unstable lesions (14.5 vs. 15.8%; odds ratio 0.90; 95% CI 0.51–1.59) did not differ between the groups. In patients with ischaemic ECG patterns, maximum levels of serum troponin-T (μg/L) were higher [0.595 (interquartile range 0.243–1.430) vs. 0.359 (0.159–0.845); ratio of geometric means 1.58; 1.13–2.20] and left ventricular function (%) was worse (44.7 ± 12.5 vs. 49.9 ± 13.3; mean difference −5.13; 95% CI −8.84 to −1.42). Adjusted for age and time to return of spontaneous circulation, ischaemic ECG patterns were no longer associated with survival. Conclusion Post-arrest ischaemic ECG patterns were associated with worse 90-day survival. A higher sum of ST-depression was associated with lower survival. Adjusted for age and time to return of spontaneous circulation, ischaemic ECG patterns were no longer associated with survival.

Aims The recent 4S-AF (scheme proposed by the 2020 ESC AF guidelines to address stroke risk, symptom severity, severity of AF burden and substrate of AF to provide a structured phenotyping of AF patients in clinical practice to guide therapy and assess prognosis) scheme has been proposed as a structured scheme to characterize patients with atrial fibrillation (AF). We aimed to assess whether the 4S-AF scheme predicts AF progression in patients with self-terminating AF. Methods and results We analysed 341 patients with self-terminating AF included in the well-phenotyped Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilization in the Progression of AF (RACE V) study. Patients had continuous monitoring with implantable loop recorders or pacemakers. AF progression was defined as progression to persistent or permanent AF or progression of self-terminating AF with >3% burden increase. Progression of AF was observed in 42 patients (12.3%, 5.9% per year). Patients were given a score based on the components of the 4S-AF scheme. Mean age was 65 [interquartile range (IQR) 58–71] years, 149 (44%) were women, 103 (49%) had heart failure, 276 (81%) had hypertension, and 38 (11%) had coronary artery disease. Median CHA2DS2-VASc (the CHA2DS2–VASc score assesses thromboembolic risk. C, congestive heart failure/left ventricular dysfunction; H, hypertension; A2, age ≥ 75 years; D, diabetes mellitus; S2, stroke/transient ischaemic attack/systemic embolism; V, vascular disease; A, age 65–74 years; Sc, sex category (female sex)) score was 2 (IQR 2–3), and median follow-up was 2.1 (1.5–2.6) years. The average score of the 4S-AF scheme was 4.6 ± 1.4. The score points from the 4S-AF scheme did not predict the risk of AF progression [odds ratio (OR) 1.1 95% CI 0.88–1.41, C-statistic 0.53]. However, excluding the symptoms domain, resulting in the 3S-AF (4S-AF scheme without the domain symptom severity, only including stroke risk, severity of AF burden and substrate of AF) scheme, predicted the risk of progression (OR 1.59 95% CI 1.15–2.27, C-statistic 0.62) even after adjusting for sex and age. Conclusions In self-terminating AF patients, the 4S-AF scheme does not predict AF progression. The 3S-AF scheme, excluding the symptom domain, may be a more appropriate score to predict AF progression. Trial registration numbers Clinicaltrials.gov NCT02726698 for RACE V

Despite significant advances in its detection, understanding and management, atrial fibrillation (AF) remains a highly prevalent cardiac arrhythmia with a major impact on morbidity and mortality of millions of patients. AF results from complex, dynamic interactions between risk factors and comorbidities that induce diverse atrial remodelling processes. Atrial remodelling increases AF vulnerability and persistence, while promoting disease progression. The variability in presentation and wide range of mechanisms involved in initiation, maintenance and progression of AF, as well as its associated adverse outcomes, make the early identification of causal factors modifiable with therapeutic interventions challenging, likely contributing to suboptimal efficacy of current AF management. Computational modelling facilitates the multilevel integration of multiple datasets and offers new opportunities for mechanistic understanding, risk prediction and personalized therapy. Mathematical simulations of cardiac electrophysiology have been around for 60 years and are being increasingly used to improve our understanding of AF mechanisms and guide AF therapy. This narrative review focuses on the emerging and future applications of computational modelling in AF management. We summarize clinical challenges that may benefit from computational modelling, provide an overview of the different in silico approaches that are available together with their notable achievements, and discuss the major limitations that hinder the routine clinical application of these approaches. Finally, future perspectives are addressed. With the rapid progress in electronic technologies including computing, clinical applications of computational modelling are advancing rapidly. We expect that their application will progressively increase in prominence, especially if their added value can be demonstrated in clinical trials., Graphical Abstract

Europace : the European journal of pacing, arrhythmias and cardiac electrophysiology 24(6), 1037-1038 (2022). doi:10.1093/europace/euab317, Published by Oxford Univ. Press, Oxford

Background Direct oral anticoagulants are available for patients with atrial fibrillation. Objective This study compared adherence and persistence of once-daily (QD) vs twice-daily (BID) direct oral anticoagulants in patients with atrial fibrillation. Methods A cohort study was conducted in three databases in the Netherlands, Italy and Germany. Patients with AF starting direct oral anticoagulants after drug approval date were included. The index date was the date of first dispensing. Study patients were restricted to those aged >= 18 years, >= 1 year database history and >= 1 year follow-up. Adherence to treatment was defined as the proportion of days covered >= 80% between the index date and the date of last dispensing of the index regimen (i.e. exposure period). The proportion of days covered was also determined during the 12-month follow-up. Persistence was defined as continuous use from index to treatment discontinuation. Results In the Netherlands, Italy and Germany, respectively, 6068, 32,260 and 167,445 patients were included. The mean age of the patients was 70, 77 and 74 years, and 31%, 40% and 61% were QD users, all respectively. Among QD/BID users, 93/90%, 88/86% and 77/58%, respectively were adherent during the exposure period. Persistence rates at 1 year in QD/BID users were 60/59%, 13/14% and 46/31%, respectively. Conclusions Adherence to treatment was high. In Germany, adherence was markedly higher in QD users compared with BID users. In Italy and the Netherlands, these differences were marginal. Persistence was low in all countries, but discontinuation was temporary. Only in Germany, persistence was markedly lower in BID users vs QD users.

BackgroundDespite improvements in the management of atrial fibrillation, patients with this condition remain at increased risk for cardiovascular complications. It is unclear whether early rhythm-control therapy can reduce this risk. MethodsIn this international, investigator-initiated, parallel-group, open, blinded-outcome-assessment trial, we randomly assigned patients who had early atrial fibrillation (diagnosed

Aims Atrial fibrillation (AF) is a progressive disease, but identifying patients at risk for AF progression is challenging. We aimed to identify factors associated with AF progression. Methods and results Atrial fibrillation progression was assessed in 392 patients with recent-onset paroxysmal or persistent AF included in the prospective, observational, multicentre identification of a risk profile to guide atrial fibrillation (AF-RISK) study. Progression of AF was assessed by Holter monitoring and 2-week event recorder at baseline and 1-year follow-up. AF progression was defined as: (i) doubling in AF burden at 1 year compared to baseline with a minimum AF burden of 10% in paroxysmal AF; or (ii) transition from paroxysmal to persistent or permanent AF; or (iii) persistent to permanent AF. Age was 60 ± 11 years, 62% were men, and 83% had paroxysmal AF. At 1 year, 52 (13%) had AF progression (11% in paroxysmal; 26% in persistent AF). Multivariable logistic regression showed that left atrial volume [odds ratio (OR) per 10 mL 1.251, 95% confidence interval (CI) 1.078–1.450; P < 0.001], N-terminal pro-B-type natriuretic peptide (NT-proBNP; OR per standard deviation increase 1.583, 95% CI 1.099–2.281; P = 0.014), and plasminogen activator inhibitor-1 (PAI-1; OR per standard deviation increase 0.660, 95% CI 0.472–0.921; P = 0.015) were associated with AF progression. In an additional follow-up of 1.9 (0.9–3.3) years patients with AF progression developed more cardiovascular events and all-cause mortality (12.4%/year vs. 2.3%/year, P < 0.001). Conclusion Atrial fibrillation progression occurred in 13% of patients with recent-onset AF during 1-year follow-up. Left atrial volume, NT-proBNP, and PAI-1 were associated with AF progression. Patients with AF progression had a higher event rate. Trial registration number Clinicaltrials.gov NCT01510210.

ObjectiveThe Rate Control versus Electrical Cardioversion Trial 7–Acute Cardioversion versus Wait and See trial compared early to delayed cardioversion for patients with recent-onset symptomatic atrial fibrillation (AF). This study aims to evaluate the adherence to a 4-week mobile health (mHealth) prescription to detect AF recurrences after an emergency department visit.MethodsAfter the emergency department visit, the 437 included patients, irrespective of randomisation arm (early or delayed cardioversion), were asked to record heart rate and rhythm for 1 min three times daily and in case of symptoms by an electrocardiography-based handheld device for 4 weeks (if available). Adherence was appraised as number of performed measurements per number of recordings asked from the patient and was evaluated for longitudinal adherence consistency. All patients who used the handheld device were included in this subanalysis.Results335 patients (58% males; median age 67 (IQR 11) years) were included. The median overall adherence of all patients was 83.3% (IQR 29.9%). The median number of monitoring days was 27 out of 27 (IQR 5), whereas the median number of full monitoring days was 16 out of 27 (IQR 14). Higher age and a previous paroxysm of AF were identified as multivariable adjusted factors associated with adherence.ConclusionsIn this randomised trial, a 4-week mHealth prescription to monitor for AF recurrences after an emergency department visit for recent-onset AF was feasible with 85.7% of patients consistently using the device with at least one measurement per day. Older patients were more adherent.Trial registration numberNCT02248753.

ObjectiveAtrial fibrillation (AF) is associated with adverse events including conduction disturbances, ventricular arrhythmias and sudden death. The aim of this study was to examine brady- and tachyarrhythmias using continuous rhythm monitoring in patients with paroxysmal self-terminating AF (PAF).MethodsIn this multicentre observational substudy to the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V), we included 392 patients with PAF and at least 2 years of continuous rhythm monitoring. All patients received an implantable loop recorder, and all detected episodes of tachycardia ≥182 beats per minute (BPM), bradycardia ≤30 BPM or pauses ≥5 s were adjudicated by three physicians.ResultsOver 1272 patient-years of continuous rhythm monitoring, we adjudicated 1940 episodes in 175 patients (45%): 106 (27%) patients experienced rapid AF or atrial flutter (AFL), pauses ≥5 s or bradycardias ≤30 BPM occurred in 47 (12%) patients and in 22 (6%) patients, we observed both episode types. No sustained ventricular tachycardias occurred. In the multivariable analysis, age >70 years (HR 2.3, 95% CI 1.4 to 3.9), longer PR interval (HR 1.9, 1.1–3.1), CHA2DS2-VASc score ≥2 (HR 2.2, 1.1–4.5) and treatment with verapamil or diltiazem (HR 0.4, 0.2–1.0) were significantly associated with bradyarrhythmia episodes. Age >70 years was associated with lower rates of tachyarrhythmias.ConclusionsIn a cohort exclusive to patients with PAF, almost half experienced severe bradyarrhythmias or AF/AFL with rapid ventricular rates. Our data highlight a higher than anticipated bradyarrhythmia risk in PAF.Trial registration numberNCT02726698.

Background The use of antiarrhythmic drugs (AADs) in patients with chronic kidney disease (CKD) is complex because impaired renal clearance can cause increased drug levels, and risk of intolerance or adverse events. Due to the propensity for CKD to occur alongside atrial fibrillation/atrial flutter (AF/AFL), it is essential that AAD safety and efficacy are assessed for patients with CKD. Hypothesis Dronedarone, an approved AAD, may present a suitable therapeutic option for patients with AF/AFL and concomitant CKD. Methods EURIDIS‐ADONIS (EURIDIS, NCT00259428; ADONIS, NCT00259376) were identically designed, multicenter, double‐blind, parallel‐group trials investigating AF/AFL control with dronedarone 400 mg twice daily versus placebo (randomized 2:1). In this post hoc analysis, the primary endpoint was time to first AF/AFL. Patients were stratified according to renal function using the CKD‐Epidemiology Collaboration equation and divided into estimated glomerular filtration rate (eGFR) subgroups of 30–44, 45–59, 60–89, and ≥90 ml/min. Time‐to‐events between treatment groups were compared using log‐rank testing and Cox regression. Results At baseline, most (86%) patients demonstrated a mild or mild‐to‐moderate eGFR decrease. Median time to first AF/AFL recurrence was significantly longer with dronedarone versus placebo for all eGFR subgroups except the 30 to 44 ml/min group, where the trend was similar but statistical power may have been limited by the small population. eGFR stratification had no significant effect on serious adverse events, deaths, or treatment discontinuations. Conclusions This analysis suggests that dronedarone could be an effective therapeutic option for AF with an acceptable safety profile in patients with impaired renal function.

The considerable mortality and morbidity associated with atrial fibrillation (AF) pose a substantial burden on patients and health care services. Although the management of AF historically focused on decreasing AF recurrence, it evolved over time in favor of rate control. Recently, more emphasis has been placed on reducing adverse cardiovascular outcomes using rhythm control, generally by using safe and effective rhythm-control therapies (typically antiarrhythmic drugs and/or AF ablation). Evidence increasingly supports early rhythm control in patients with AF that has not become long-standing, but current clinical practice and guidelines do not yet fully reflect this change. Early rhythm control may effectively reduce irreversible atrial remodeling and prevent AF-related deaths, heart failure, and strokes in high-risk patients. It has the potential to halt progression and potentially save patients from years of symptomatic AF; therefore, it should be offered more widely.

Aim The benefit of cardiac pacing in patients with severe recurrent reflex syncope and asystole induced by tilt testing has not been established. The usefulness of tilt-table test to select candidates for cardiac pacing is controversial. Methods and results We randomly assigned patients aged 40 years or older who had at least two episodes of unpredictable severe reflex syncope during the last year and a tilt-induced syncope with an asystolic pause longer than 3 s, to receive either an active (pacing ON; 63 patients) or an inactive (pacing OFF; 64 patients) dual-chamber pacemaker with closed loop stimulation (CLS). The primary endpoint was the time to first recurrence of syncope. Patients and independent outcome assessors were blinded to the assigned treatment. After a median follow-up of 11.2 months, syncope occurred in significantly fewer patients in the pacing group than in the control group [10 (16%) vs. 34 (53%); hazard ratio, 0.23; P = 0.00005]. The estimated syncope recurrence rate at 1 year was 19% (pacing) and 53% (control) and at 2 years, 22% (pacing) and 68% (control). A combined endpoint of syncope or presyncope occurred in significantly fewer patients in the pacing group [23 (37%) vs. 40 (63%); hazard ratio, 0.44; P = 0.002]. Minor device-related adverse events were reported in five patients (4%). Conclusion In patients aged 40 years or older, affected by severe recurrent reflex syncope and tilt-induced asystole, dual-chamber pacemaker with CLS is highly effective in reducing the recurrences of syncope. Our findings support the inclusion of tilt testing as a useful method to select candidates for cardiac pacing. Study registration ClinicalTrials.gov identifier NCT02324920, Eudamed number CIV-05-013546., Graphical Abstract

AIMS: Atrial fibrillation (AF) reduces quality of life (QoL). We aim to evaluate effects of targeted therapy of underlying conditions on QoL in patients with AF and heart failure (HF). METHODS AND RESULTS: The Routine versus Aggressive risk factor driven upstream rhythm Control for prevention of Early atrial fibrillation in heart failure (RACE 3) study randomized patients with early persistent AF and HF to targeted or conventional therapy. Both groups received guideline-driven treatment. The targeted group received four additional therapies: mineralocorticoid receptor antagonists; statins; angiotensin converting enzyme inhibitors and/or receptor blockers; and cardiac rehabilitation including physical activity, dietary restrictions, and counselling. Quality of life was analysed in 230 patients at baseline and 1 year with available Medical Outcomes Study Short-Form Health Survey (SF-36), University of Toronto AF Severity Scale (AFSS) questionnaires, and European Heart Rhythm Association (EHRA) class. Improvements in SF-36 subscales were larger in the targeted group for physical functioning (Δ12 ± 19 vs. Δ6 ± 22, P = 0.007), physical role limitations (Δ32 ± 41 vs. Δ17 ± 45, P = 0.018), and general health (Δ8 ± 16 vs. Δ0 ± 17, P

Summary of the progress in arrhythmias in 2020. RACE4 and ALL-IN indicated that integrated nurse-led care improves outcomes in AF patients.3 , 4 The same was reported for early rhythm control therapy15 and cryoablation as initial AF treatment.25 , 26 Subcutaneous ICD was non-inferior to classical transvenous ICD therapy in PRAETORIAN.54 One mechanistic study showed that autoantibodies against misexpressed actin, keratin, and connexin-43 proteins create a blood-borne biomarker profile enhancing diagnosis of Brugada syndrome.50 Another mechanistic study indicated that transseptal LV pacing yields similar improvement in contractility as His bundle pacing whilst being more easy to execute.44 In PRE-DETERMINE a simple-to-use ECG risk score improved risk prediction in patients with ischemic heart disease possibly enhancing appropriate ICD therapy in high risk patients.58

Background: Studies on the use of non-vitamin K antagonist oral anticoagulants in unselected patients with atrial fibrillation (AF) show that clinical characteristics and dosing practices differ per region, but lack data on edoxaban. Methods: With data from Edoxaban Treatment in routiNe clinical prActice for patients with AF in Europe (ETNA-AF-Europe), a large prospective observational study, we compared clinical characteristics (including the dose reduction criteria for edoxaban: creatinine clearance 15–50 mL/min, weight ≤60 kg, and/or use of strong p-glycoprotein inhibitors) of patients from Belgium and the Netherlands (BeNe) with those from other European countries (OEC). Results: Of all 13,639 patients in ETNA-AF-Europe, 2579 were from BeNe. BeNe patients were younger than OEC patients (mean age: 72.3 vs 73.9 years), and had lower CHA2DS2-VASc (mean: 2.8 vs 3.2) and HAS-BLED scores (mean: 2.4 vs 2.6). Patients from BeNe less often had hypertension (61.6% vs 80.4%), and/or diabetes mellitus (17.3% vs 23.1%) than patients from OEC. Moreover, relatively fewer patients in BeNe were prescribed the reduced dose of 30 mg edoxaban (14.8%) than in OEC (25.4%). Overall, edoxaban was dosed according to label in 83.1% of patients. Yet, 30 mg edoxaban was prescribed in the absence of any dose reduction criteria in 36.9% of 30 mg users (5.5% of all patients) in BeNe compared with 35.5% (9.0% of all patients) in OEC. Conclusion: There were several notable differences between BeNe and OEC regarding clinical characteristics and dosing practices in patients prescribed edoxaban, which are relevant for the local implementation of dose evaluation and optimisation. Trial registration: NCT02944019; Date of registration: October 24, 2016., SCOPUS: ar.j, info:eu-repo/semantics/published

Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients.Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint-echocardiographic reduction of left ventricular end-systolic volume (LVESV)-were evaluated.The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area109μVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration150 ms, PR interval ≥ 230 ms, and in QRS area109 μVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 μVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT.In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT.

BACKGROUND: Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously.METHODS: In a multicenter, randomized, open-label, noninferiority trial, we randomly assigned patients with hemodynamically stable, recent-onset (RESULTS: The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P = 0.005 for noninferiority). In the delayed-cardioversion group, conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients (69%) and after delayed cardioversion in 61 patients (28%). In the early-cardioversion group, conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients (16%) and after cardioversion in 171 patients (78%). Among the patients who completed remote monitoring during 4 weeks of follow-up, a recurrence of atrial fibrillation occurred in 49 of 164 patients (30%) in the delayed-cardioversion group and in 50 of 171 (29%) in the early-cardioversion group. Within 4 weeks after randomization, cardiovascular complications occurred in 10 patients and 8 patients, respectively.CONCLUSIONS: In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. (Funded by the Netherlands Organization for Health Research and Development and others; RACE 7 ACWAS ClinicalTrials.gov number, NCT02248753.).

BASIK2 is a prospective, double-blind, randomized placebo-controlled trial investigating the effect of vitamin K2 (menaquinone-7;MK7) on imaging measurements of calcification in the bicuspid aortic valve (BAV) and calcific aortic valve stenosis (CAVS). BAV is associated with early development of CAVS. Pathophysiologic mechanisms are incompletely defined, and the only treatment available is valve replacement upon progression to severe symptomatic stenosis. Matrix Gla protein (MGP) inactivity is suggested to be involved in progression. Being a vitamin K dependent protein, supplementation with MK7 is a pharmacological option for activating MGP and intervening in the progression of CAVS. Forty-four subjects with BAV and mild–moderate CAVS will be included in the study, and baseline 18F-sodiumfluoride (18F-NaF) positron emission tomography (PET)/ magnetic resonance (MR) and computed tomography (CT) assessments will be performed. Thereafter, subjects will be randomized (1:1) to MK7 (360 mcg/day) or placebo. During an 18-month follow-up period, subjects will visit the hospital every 6 months, undergoing a second 18F-NaF PET/MR after 6 months and CT after 6 and 18 months. The primary endpoint is the change in PET/MR 18F-NaF uptake (6 months minus baseline) compared to this delta change in the placebo arm. The main secondary endpoints are changes in calcium score (CT), progression of the left ventricularremodeling response and CAVS severity (echocardiography). We will also examine the association between early calcification activity (PET) and later changes in calcium score (CT).

Aims Cardiac involvement is the main determinant of poor outcomes in sarcoidosis. Right ventricular (RV) dysfunction and left ventricular (LV) late gadolinium enhancement (LGE) have been reported to be predictive of adverse outcome in non‐ischaemic cardiomyopathies. The aim of our study was to determine whether delayed RV LGE with cardiovascular magnetic resonance would be predictive of adverse events in addition to LV LGE during the long‐term follow‐up of pulmonary sarcoidosis patients. Methods and results Eighty‐four consecutive biopsy‐proven pulmonary sarcoidosis patients were followed for a median of 56 months [38–74] after baseline delayed contrast‐enhanced cardiac magnetic resonance. The composite primary endpoint consisted of admission for congestive heart failure, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy, pacemaker implantation for high degree atrio‐ventricular block, or cardiac death. The composite secondary endpoint included all‐cause mortality in addition to the primary endpoint. RV and LV LGE were demonstrated in respectively 12 and 27 patients. Five of 10 events included in the primary endpoint occurred in the group with RV LGE. RV LGE, LV, or biventricular LGE yielded Cox hazard ratios of 8.71 [95% confidence interval (CI) 1.90–23.81], 9.22 (95% CI 1.96–43.45), and 12.09 (95% CI 3.43–42.68) for the composite primary endpoint. In a multivariate model, the predictive value of biventricular LGE for the composite primary and secondary endpoints was strongest. Kaplan–Meier event‐free survival curves were most significant for RV LGE and biventricular LGE (log rank with P < 0.001). Conclusions Biventricular LGE at presentation is the strongest, independent predictor of adverse outcome during long‐term follow‐up. Asymptomatic myocardial scar

We assessed 1-year outcomes in patients with atrial fibrillation enrolled in the EurObservational Research Programme AF General Pilot Registry (EORP-AF), in relation to kidney function, as assessed by glomerular filtration rate (eGFR). In a cohort of 2398 patients (median age 69 years; 61% male), eGFR (ml/min/1.73 m2) calculated using the CKD-EPI formula was ≥80 in 35.1%, 50–79 in 47.2%, 30–49 in 13.9% and

Objectives: To review the value of delayed contrast-enhanced cardiac magnetic resonance (CECMR) in differentiating patients with cardiac sarcoidosis (CS) from those with coronary artery disease and recent myocardial infarctions. Background: Late gadolinium enhancement (LGE) accurately delineates myocardial necrosis or fibrosis. The pattern of LGE in ischemic and non-ischemic myocardial disease is different, and might be helpful in distinguishing CS from ischemic disease. Methods: The CECMR studies of 30 patients with CS were compared to those performed in 30 consecutive infarct patients, who had been managed with primary coronary interventions, and 10 healthy controls. Two experienced blinded observers classified patients by assessing the distribution of LGE. Results: LV LGE was present in 29/30 CS (mean 3.8 segments, range 0-12), all infarct (mean 4.3 segments, range 0-9), and none of the patients in the control group. The amount of LV LGE did not differ significantly between CS and infarct patients (19 ± 11% and 19 ± 12%, P= 0.8). The CS group exhibited a predominantly patchy, 3 layer LGE (P = 0.01), whereas confluent transmural LGE (P = 0.04) with a vascular distribution (P < 0.001) was prevalent in the infarct group. Significantly more RV LGE (P = 0.01) and dilation (P = 0.02) were found in the CS group. The two observers classified patients correctly as CS in 72% and 83% of cases, as ischemic in nature in 77% and 80% of cases, and as normal in 90% and 100% respectively. Conclusions: Gadolinium CMR was helpful in differentiating patients with CS from patients with ischemic heart disease and previous myocardial infarctions. In a subgroup of ischemic patients the pattern of LGE was atypical, and suggestive of non-ischemic etiology. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 307-314)

Aims Despite its proven efficacy, the Cox-Maze III procedure did not gain widespread acceptance for the treatment of stand-alone atrial fibrillation (SA-AF) because of its complexity and technical difficulty. Surgical ablation for SA-AF can now be successfully performed utilizing minimally invasive surgery (MIS). This study provides an overview of state-of-the-art MIS for the treatment of SA-AF. Methods and results Studies selected for this review were identified on PUBMED and exclusion and inclusion criteria were applied to select the publication to be screened. Twenty-eight studies were included; 27 (96.4%) were observational in nature whereas 1 was prospective non-randomized. The total number of patients was 1051 (range 14–114). Mean age ranged from 45.3 to 67.1 years. Suboptimal results were obtained when employing microwave and high focused ultrasound energies. In contrast, MIS ablation of SA-AF achieved satisfactory 1-year results when the bipolar radiofrequency was employed as energy source, with antiarrhythmic drug-free success rate comparable to percutaneous catheter ablation (PCA). The success rate in paroxysmal was even higher than in PCA. In contrast, ganglionated plexi ablation and left atrial appendage removal seem not to influence the recurrence of AF and the occurrence of postoperative thromboembolic events. Conclusion Minimally invasive surgery ablation of SA-AF achieved satisfactory 1-year results when the bipolar radiofrequency was employed. Nevertheless, the relatively high complication rate reported suggest that such techniques require further refinement. Finally, the preliminary results of the hybrid approach are promising but they need to be confirmed.

Aims Recent increases in heart failure tend to overload the healthcare system. Consequently, there is a need for innovative strategies to reduce heart failure hospitalizations. Methods and results A multicentre randomized controlled trial was carried out to test the hypothesis that telemonitoring reduces heart failure hospitalizations during 1 year follow-up. The mean age of the 382 participating patients was 71.5 (32–93) years; the mean left ventricular ejection fraction was 0.38, and in 61% it was ≤0.45%. Mean time to first heart failure-related hospitalization was 161 days for the intervention group and 139 days for the usual-care group; hospitalizations occurred in 18 (9.1%) compared with 25 (13.5%) patients, with a total number of 24 and 43 hospitalizations, respectively [Kaplan–Meier P = 0.151, hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.35–1.17]. Subgroup analysis of the primary endpoint showed benefits for three subgroups: duration of heart failure, having a pacemaker, and co-habiting. The combined endpoint of heart failure admission and all-cause mortality was similar for both groups (Kaplan–Meier P = 0.641, HR 0.89, 95% CI 0.69–1.83). No differences were found regarding secondary endpoints, except for the reduced number of face to face contacts with the heart failure nurse (Mann–Whitney P < 0.001). Mortality was 18 (9.1%) in the intervention group and 12 (6.5%) in the usual-care group (Mann–Whitney P = 0.34, Cox regression analysis P = 0.82). Conclusion No significant differences were found regarding the primary endpoint, possibly caused by a relative underpowering of the population combined with well-treated study groups. However, telemonitoring tends to reduce heart failure (re)admissions and significantly decreases contacts with specialized nurses. Further research with pre-specified groups, as found in the subgroup analysis, is needed.

The multifactorial pathogenesis leading to dilated cardiomyopathy (DCM) makes stratification difficult. The recent MOGE(S) (morphofunctional, organ involvement, genetic or familial, etiology, stage) classification addresses this issue.The purpose of this study was to investigate the applicability and prognostic relevance of the MOGE(S) classification in patients with DCM.This study used patients from the Maastricht Cardiomyopathy Registry in the Netherlands and excluded patients with ischemic, valvular, hypertensive, and congenital heart disease. All other patients underwent a complete diagnostic work-up, including genetic evaluation and endomyocardial biopsy.A total of 213 consecutive patients with DCM were included: organ involvement was demonstrated in 35 (16%) and genetic or familial DCM in 70 (33%) patients, including 16 (8%) patients with a pathogenic mutation. At least 1 cause was found in 155 (73%) patients, of whom 48 (23%) had more than 1 possible cause. Left ventricular reverse remodeling was more common in patients with nongenetic or nonfamilial DCM than in patients with genetic or familial DCM (40% vs. 25%; p = 0.04). After a median follow-up of 47 months, organ involvement and higher New York Heart Association functional class were associated with adverse outcome (p0.001 and p = 0.02, respectively). Genetic or familial DCM per se was of no prognostic significance, but when it was accompanied by additional etiologic-environmental factors such as significant viral load, immune-mediated factors, rhythm disturbances, or toxic triggers, a worse outcome was revealed (p = 0.03). A higher presence of MOGE(S) attributes (≥2 vs. ≤1 attributes) showed an adverse outcome (p = 0.007).The MOGE(S) classification in DCM is applicable, and each attribute or the gene-environment interaction is associated with outcome. Importantly, the presence of multiple attributes was a strong predictor of adverse outcome. Finally, adaptation of the MOGE(S) involving multiple possible etiologies is recommended.

This study sought to compare age-related differences in presentation, treatment, and outcome of atrial fibrillation (AF) in a wide cohort of European subjects.AF is the most common sustained arrhythmia in the elderly.We evaluated all patients enrolled in the EORP-AF (EURObservational Research Programme-Atrial Fibrillation) General Pilot Registry in 70 centers of 9 European countries.Among 3,119 subjects, 1,051 (33.7%) were age ≥75 years. Permanent AF was significantly more common in the elderly, who had a higher prevalence of hypertension, valvular diseases, chronic heart failure, coronary artery disease, renal failure, chronic obstructive pulmonary disease, and prior hemorrhagic event or a transient ischemic attack. Common diagnostic tests were underused in older subjects. Despite their higher stroke risk, the use of oral anticoagulants was significantly lower in the elderly (76.7% vs. 82.8%; p = 0.0012), whereas aspirin and clopidogrel alone or in combination were more often prescribed. Rate control was the management of choice in the older group, with electrical cardioversion and catheter ablation performed less frequently than in the younger age group. Antiarrhythmic drugs were significantly less prescribed in the elderly (29.8% vs. 41.7%; p 0.0001). At the 1-year follow-up, mortality (11.5% vs. 3.7%; p 0.0001) and the composite of stroke/transient ischemic attack, systemic thromboembolism, and/or death (13.6% vs. 4.9%; p 0.0001) were significantly higher in the ≥75 years of age cohort.In older patients, AF is more often associated with comorbidities. Rate control is the preferred therapeutic approach. Despite a higher CHA

The purpose of this study was too describe the associated baseline features of AF patients with heart failure (HF) with reduced and preserved ejection fraction (HFrEF and HFpEF). Secondly, we assessed symptomatic status and their clinical correlates. Finally, we examined independent predictors for 'heart failure' at the 1-year follow-up period.A survey of European cardiologists from nine countries, participating in the EURObservational Research Programme Pilot survey on Atrial Fibrillation (EORP-AF Pilot), was carried out. Of the whole cohort of 2972 patients, 1411 (47.5%) had a diagnosis of HF. Of the AF patients with HF, oral anticoagulants were prescribed to 82.1% and antiarrhythmic drugs in 36.7%. Independent predictors of HFpEF were high body mass index, high heart rate, high systolic blood pressure, low diastolic blood pressure, high CHA2DS2-VASc score, and absence of chronic kidney disease, sleep apnoea, or ischaemic cardiomyopathy. On multivariate stepwise regression analysis, independent predictors of the development of HF were mode of AF presentation, diuretic use, prior HF, COPD, and valvular disease. At 1 year, HF was associated with a greater risk of all-cause mortality (log-rank test, P0.001). When HFrEF was compared with HFpEF at 1 year, crude rates were significant for the composite endpoint of 'stroke/thrombo-embolism/transient ischaemic attack and death' (15.9% vs. 11.1%, P = 0.043).We provide insights into the clinical characteristics and outcomes in AF patients with HF, who were managed by European cardiologists. Despite a high prevalence of oral anticoagulant use, 1-year mortality and morbidity remained high in AF patients with HF, whether HFrEF or HFpEF. Such patients require a holistic approach to cardiovascular risk management.

We evaluated the safety and effectiveness of the hybrid thoracoscopic endocardial epicardial technique for the treatment of lone atrial fibrillation.Between 2009 and 2012, a cohort of 78 consecutive patients (median age 60.5 years, 77% male) underwent ablation of atrial fibrillation (AF) as a stand-alone procedure using a thoracoscopic, hybrid epicardial-endocardial technique. All patients underwent continuous 7-day Holter monitoring at 3 months, 6 months, 1 year and yearly thereafter. All patients reached 1-year follow-up. Median follow-up was 24 months [interquartile range 12-36].No death or conversion to cardiopulmonary bypass occurred. No patient demonstrated paralysis of the phrenic nerve. Overall, the incidence of perioperative complications was 8% (n=6). At the end of follow-up, sixty-eight patients (87%) were in sinus rhythm (SR) with no episode of AF, atrial flutter or atrial tachycardia lasting longer than 30 seconds and off antiarrhythmic drugs (ADD). Among patients with long-standing persistent AF, 15 (100%) were in SR and off AAD. Success rates were 82% (n=28) in persistent and 76% (n=22) in paroxysmal AF (P=0.08). No patient died and no thromboembolic/bleeding events or procedure-related complications occurred during the follow-up.Thoracoscopic hybrid epicardial endocardial technique proved to be effective and safe in the treatment of LAF and to represent an important new suitable option to treat stand-alone AF. Our findings need to be confirmed by further larger studies.

This study sought to investigate differences in outcome between patients treated with successful strict, failed strict, and lenient rate control.The RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation) study showed no difference in outcome between lenient and strict rate control in patients with permanent atrial fibrillation (AF). However, in the strict group not all patients achieved the pre-defined heart rate target.The primary outcome was a composite of cardiovascular morbidity and mortality. For the current analysis outcome events were analyzed from end of the dose-adjustment phase until end of follow-up (median 2.9 years [interquartile range: 2.4 to 3.0 years]). Of 614 patients, 608 completed the dose-adjustment phase-301 in the strict (resting heart rate80 beats/min, and during moderate exercise110 beats/min) and 307 in the lenient group (resting heart rate110 beats/min). In the strict group, 203 of 301 patients achieved the rate control target, and 98 failed.Heart rate was different after the dose-adjustment phase between the successful strict (72 ± 7 beats/min), failed strict (86 ± 14 beats/min), and lenient (93 ± 8 beats/min) group (p0.001) and remained significantly different during follow-up. The primary outcome was reached in 27 of 203 (14.2% KM estimate) in the successful strict versus 14 of 98 (15%) in the failed strict versus 35 of 307 (12.1%) in the lenient group (p = 0.5). The components of the primary outcome and quality of life were similar in the groups.In patients with permanent AF, successful strict rate control does not improve outcome. Therefore, lenient rate control might be frontline therapy.

Atrial fibrillation (AF) is the most frequent sustained arrhythmia of elderly patients, in whom it determines an increase in morbidity and mortality. Aim of this study was to assess age-related differences in the characteristics, management and prognosis of patients with AF in European cardiology practices.The Euro Heart Survey on AF was an observational study sponsored by the European Society of Cardiology. Patients were enrolled between 2003 and 2004 in 182 hospitals of 35 countries. For the purposes of this study, they were categorized into three age-groups:65 (n=2124), 65-80 (n=2534) and80 years (n=671). Follow-up was closed in 2005.Compared with general population estimates, patients80 years were underrepresented in the Euro Heart Survey. The oldest patients were less likely to be enrolled by university or specialized centers, to receive extensive diagnostic testing, and to receive oral anticoagulation despite a worse stroke risk profile. Furthermore, the oldest patients less often received rhythm control therapy, even when presenting with palpitations and non-permanent AF. During 1 year follow-up, elderly patients more often suffered a myocardial infarction, new onset heart failure and major bleedings. They had higher all-cause and cardiovascular mortality.Elderly patients with AF are less often referred to the cardiologist and, based on current guidelines, are inadequately studied and treated, compared to younger counterparts. Education on evidence- based management and the design of randomized controlled trials specifically targeting the elderly, should improve the management and prognosis of this frail segment of the AF population.

The aim of this study was to investigate the influence of rate control on quality of life (QOL).The RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation II) trial showed that lenient rate control is not inferior to strict rate control in terms of cardiovascular morbidity and mortality. The influence of stringency of rate control on QOL is unknown.In RACE II, a total of 614 patients with permanent atrial fibrillation (AF) were randomized to lenient (resting heart rate [HR]110 beats/min) or strict (resting HR80 beats/min, HR during moderate exercise110 beats/min) rate control. QOL was assessed in 437 patients using the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) questionnaire, AF severity scale, and Multidimensional Fatigue Inventory-20 (MFI-20) at baseline, 1 year, and end of study. QOL changes were related to patient characteristics.Median follow-up was 3 years. Mean age was 68 ± 8 years, and 66% were males. At the end of follow-up, all SF-36 subscales were comparable between both groups. The AF severity scale was similar at baseline and end of study. At baseline and at end of study there were no differences in the MFI-20 subscales between the 2 groups. Symptoms at baseline, younger age, and less severe underlying disease, rather than assigned therapy or heart rate, were associated with QOL improvements. Female sex and cardiovascular endpoints during the study were associated with worsening of QOL.Stringency of heart rate control does not influence QOL. Instead, symptoms, sex, age, and severity of the underlying disease influence QOL. (Rate Control Efficacy in Permanent Atrial Fibrillation; NCT00392613).

The aim of this study was to evaluate echocardiographic remodeling in permanent atrial fibrillation (AF) patients treated with either lenient or strict rate control.It is unknown whether in permanent AF, lenient rate control is associated with more adverse cardiac remodeling than strict rate control.Echocardiography was conducted at baseline and at follow-up in 517 patients included in the RACE II (RAte Control Efficacy in permanent atrial fibrillation II) trial. Echocardiographic parameters were compared between patients randomized to lenient rate control (n = 261) or strict rate control (n = 256).Baseline echocardiographic parameters were comparable between patients randomized to lenient and strict rate control. Between baseline and follow-up, significant adverse atrial or ventricular remodeling was not observed in either group. There were also no significant differences in atrial and ventricular remodeling between patients who continuously had heart rates between 80 and 110 beats/min and patients who continuously had heart rates80 beats/min during follow-up. Lenient rate control was not independently associated with changes in echocardiographic parameters: mean adjusted effect on left atrial size was 1.6 mm (p = 0.09) and 1.1 mm on left ventricular end-diastolic diameter (p = 0.23). Instead, female sex was independently associated with adverse remodeling: mean adjusted effect on left atrial size was 2.4 mm (p = 0.02) and 6.5 mm on left ventricular end-diastolic diameter (p0.0001).Female sex, not lenient rate control, seemed to be associated with significant adverse cardiac remodeling in patients with permanent AF such as those enrolled in the RACE II study. (RAte Control Efficacy in Permanent Atrial Fibrillation [RACE II]; NCT00392613).