H. J. G. M. Crijns

Routine versus aggressive upstream rhythm control for prevention of early atrial fibrillation in heart failure: background, aims and design of the RACE 3 study.

BackgroundRhythm control for atrial fibrillation (AF) is cumbersome because of its progressive nature caused by structural remodelling. Upstream therapy refers to therapeutic interventions aiming to modify the atrial substrate, leading to prevention of AF.ObjectiveThe Routine versus Aggressive upstream rhythm Control for prevention of Early AF in heart failure (RACE 3) study hypothesises that aggressive upstream rhythm control increases persistence of sinus rhythm compared with conventional rhythm control in patients with early AF and mild-to-moderate early systolic or diastolic heart failure undergoing electrical cardioversion.DesignRACE 3 is a prospective, randomised, open, multinational, multicenter trial. Upstream rhythm control consists of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, mineralocorticoid receptor antagonists, statins, cardiac rehabilitation therapy, and intensive counselling on dietary restrictions, exercise maintenance, and drug adherence. Conventional rhythm control consists of routine rhythm control therapy without cardiac rehabilitation therapy and intensive counselling. In both arms, every effort is made to keep patients in the rhythm control strategy, and ion channel antiarrhythmic drugs or pulmonary vein ablation may be instituted if AF relapses. Total inclusion will be 250 patients. If upstream therapy proves to be effective in improving maintenance of sinus rhythm, it could become a new approach to rhythm control supporting conventional pharmacological and non-pharmacological rhythm control.

Feasibility of TEE-guided stroke risk assessment in atrial fibrillation-background, aims, design and baseline data of the TIARA pilot study

BackgroundAntithrombotic management in atrial fibrillation (AF) is currently based on clinical characteristics, despite evidence of potential fine-tuning with transoesophageal echocardiography (TEE). This open, randomised, multicentre study addresses the hypothesis that a comprehensive strategy of TEE-based aspirin treatment in AF patients is feasible and safe.MethodsBetween 2005 and 2009, ten large hospitals in the Netherlands enrolled AF patients with a moderate risk of stroke. Patients without thrombogenic TEE characteristics were randomised to aspirin or vitamin K antagonists (VKA). The primary objective is to show that TEE-based aspirin treatment is safe compared with VKA therapy. The secondary objective tests feasibility of TEE as a tool to detect echocardiographic features of high stroke risk. This report compares randomised to non-randomised patients and describes the feasibility of a TEE-based approach.ResultsIn total, 310 patients were included. Sixty-nine patients were not randomised because of non-visualisation (nu2009=u20096) or TEE risk factors (nu2009=u200963). Compared with non-randomised patients, randomised patients (nu2009=u2009241) were younger (65u2009±u200911 vs. 69u2009±u20099xa0years, pu2009=u20090.004), had less coronary artery disease (9 vs. 20%, pu2009=u20090.018), previous TIA (1.7 vs. 7.2%, pu2009=u20090.029), AF during TEE (25 vs. 54%, pu2009<u20090.001), mitral incompetence (55 vs. 70%, pu2009=u20090.038), VKA use (69 vs. 82%, pu2009=u20090.032), had a lower mean CHADS2 score (1.2u2009±u20090.6 vs. 1.6u2009±u20091.0, pu2009=u20090.004), and left ventricular ejection fraction (59u2009±u20098 vs. 56u2009±u20098%, pu2009=u20090.016).ConclusionsThis study shows that a TEE-based approach for fine-tuning stroke risk in AF patients with a moderate risk for stroke is feasible. Follow-up data will address the safety of this TEE-based approach.

Coronary artery-bronchial artery fistulas: report of two Dutch cases with a review of the literature

BackgroundCoronary bronchial artery fistulas (CBFs) are rare anomalies, which may be isolated or associated with other disorders.Materials and methodsTwo adult patients with CBFs are described and a PubMed search was performed using the keywords “coronary bronchial artery fistulas” in the period from 2008 to 2013.ResultsTwenty-seven reviewed subjects resulting in a total of 31 fistulas were collected. Asymptomatic presentation was reported in 5 subjects (19xa0%), chest pain (nu2009=u200917) was frequently present followed by haemoptysis (nu2009=u20097) and dyspnoea (nu2009=u20095). Concomitant disorders were bronchiectasis (44xa0%), diabetes (33xa0%) and hypertension (28xa0%). Multimodality and single-modality diagnostic strategies were applied in 56xa0% and 44xa0%, respectively. The origin of the CBFs was the left circumflex artery in 61xa0%, the right coronary artery in 36xa0% and the left anterior descending artery in 3xa0%. Management was conservative (22xa0%), surgical ligation (11xa0%), percutaneous transcatheter embolisation (30xa0%), awaiting lung transplantation (7xa0%) or not reported (30xa0%).ConclusionsCBFs may remain clinically silent, or present with chest pain or haemoptysis. CBFs are commonly associated with bronchiectasis and usually require a multimodality approach to be diagnosed. Several treatment strategies are available. This report presents two adult cases with CBFs and a review of the literature.

Right ventricular function in dilated cardiomyopathy and ischemic heart disease: assessment with non-invasive imaging

BackgroundDilated cardiomyopathy and ischaemic heart disease can both lead to right ventricular (RV) dysfunction. Direct comparisons of the two entities regarding RV size and function using state-of-the-art imaging techniques have not yet been performed. We aimed to determine RV function and volume in dilated cardiomyopathy and ischaemic heart disease in relation to left ventricular (LV) systolic and diastolic function and systolic pulmonary artery pressure.Methods and resultsA well-characterised group (cardiac magnetic resonance imaging, echocardiography, coronary angiography and endomyocardial biopsy) of 46 patients with dilated cardiomyopathy was compared with LV ejection fraction (EF)-matched patients (nu2009=u200923) with ischaemic heart disease. Volumes and EF were determined with magnetic resonance imaging, diastolic LV function and pulmonary artery pressure with echocardiography.After multivariable linear regression, four factors independently influenced RVEF (R2u2009=u20090.51, pu2009<u20090.001): LVEF (ru2009=u20090.54, pu2009<u20090.001), ratio of peak early and peak atrial transmitral Doppler flow velocity as measure of LV filling pressure (ru2009=u2009−u20090.52, pu2009<u20090.001) and tricuspid regurgitation flow velocity as measure of pulmonary artery pressure (ru2009=u2009−u20090.38, pu2009=u20090.001). RVEF was significantly worse in patients with dilated cardiomyopathy compared with ischaemic heart disease: median 48u2009% (interquartile range (IQR) 37–55u2009%) versus 56u2009% (IQR 48–63u2009%), pu2009<u20090.05.ConclusionsIn patients with dilated cardiomyopathy and ischaemic heart disease, RV function is determined by LV systolic and diastolic function, the underlying cause of LV dysfunction, and pulmonary artery pressure. It was demonstrated that RV function is more impaired in dilated cardiomyopathy.

Stroke risk in patients with device-detected atrial high-rate episodes

Cardiovascular implantable electronic devices (CIEDs) can detect atrial arrhythmias, i.u2009e. atrial high-rate episodes (AHRE). The thrombo-embolic risk in patients showing AHRE appears to be lower than in patients with clinical atrial fibrillation (AF) and it is unclear whether the former will benefit from oral anticoagulants. Based on currently available evidence, it seems reasonable to consider antithrombotic therapy in patients without documented AF showing AHRE >24xa0hours and axa0CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75xa0years [doubled], diabetes mellitus, prior stroke [doubled], vascular disease, age 65–74xa0years and female sex) ≥1, awaiting definite answers from ongoing randomised clinical trials. In patients with AHRE <24xa0hours, current literature does not support starting oral anticoagulation. In these patients, intensifying CIED read-outs can be considered to find progression in AHRE duration sooner, enhancing timely stroke prevention. The notion that AHRE and stroke coincide perseveres but should be abandoned since CIED data show axa0clear disconnect.

Rate control in atrial fibrillation, insight into the RACE II study

Currently, in Europe, more than 6 million patients have atrial fibrillation (AF) [1]. It is expected that this number will double in the next 30–50xa0years [1–3]. With AF, the risk of death, stroke and heart failure is increased [4–6], and exercise capacity and quality of life are reduced [7, 8]. Thus, AF is not a benign disease. Despite efforts to maintain sinus rhythm, AF is a progressive arrhythmia [9–11] and many patients eventually develop permanent AF. Until recently, the treatment of this specific patient group was not evidence based. An evidence-based treatment strategy is indispensable considering the large patient population. n nIt was not until the beginning of this decade that it became apparent that it was not the rhythm that determined the prognosis, i.e. there was no difference in outcome between rate (treatment aimed at heart rate reduction) and rhythm control (treatment aimed at restoration and maintenance of sinus rhythm) [12–18]. However, different definitions of adequate rate control were used in the rate versus rhythm control studies (Tablexa01). The guidelines at that time advocated a strict rate-control strategy, but this was based on small, short-term studies which did not investigate prognosis [19]. Thus, an evidence-based rate-control strategy was lacking. Studies which investigated different rate-control strategies showed no difference in outcome between patients with a high and low heart rate [20, 21]. However, these were all retrospective analyses. n n n nTable 1 n nHeart rate criteria used in the rate- versus rhythm-control trials n n n n nRationale to initiate the RACE II study nDrugs frequently used to institute rate control consist of beta-blockers, non-dihydropyridine calcium-channel blockers and digoxin. From the 1970s until now, several studies have been performed evaluating the effect of negative dromotropic drugs (beta-blockers, non-dihydropyridine calcium-channel blockers, digoxin, amiodarone, and dronedarone) on heart rate during AF. At first, the focus was on heart rate at rest and during exercise [22–26]. It was expected that exercise capacity would improve due to a reduction in heart rate. Surprisingly, however, later studies showed no improvement of exercise capacity with a more physiological rate response during exercise [27–33]. n nThe previous guidelines recommended the use of strict rate control [19] to reduce symptoms, improve the quality of life and exercise tolerance, reduce heart failure, and improve survival. On the other hand, strict rate control could cause drug-related adverse effects, including bradycardia, syncope, and a need for pacemaker implantation. Thus, the balance between benefit and risk in terms of cardiovascular morbidity and mortality, quality of life, exercise tolerance, and disease burden remained unknown. n nOne of the first studies on heart rate during AF and prognosis was a large retrospective analysis of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) [20]. All patients randomised to rate control in AFFIRM who were in AF at baseline and at 2xa0months follow-up were included in this analysis. The patients were stratified according to the quartiles of resting heart rate at 2xa0months. There was no difference in cardiovascular hospitalisation or death between the quartiles of achieved heart rate at rest at 2-month follow-up. Resting heart rate was not a predictor for all-cause mortality or cardiovascular hospitalisation. Importantly, in AFFIRM a strict rate-control approach was used, as the guidelines advocated at that time (Tablexa01). To achieve the strict rate-control targets frequent drug changes were needed; eventually, the rate-control criteria were achieved in two-thirds of the patients [34]. In the RAte Control versus Electrical cardioversion (RACE) study the rate-control criterion was a resting heart rate below 100 beats per minute [14]. This criterion was solely established on the basis of the clinical experience of the principal investigators that 100 beats per minute would be most feasible as well as clinically relevant in terms of maintaining. A pooled analysis of AFFIRM and RACE evaluated differences in outcome between the studies [35]. In that study patients were included if they met a combination of overlapping inclusion and exclusion criteria of AFFIRM and RACE. The primary endpoint was a composite of all-cause mortality, cardiovascular hospitalisation, and myocardial infarction. In total, 1091 patients were included, 874 from AFFIRM and 217 from RACE. The mean heart rate in the AFFIRM patients was lower compared with the patients from RACE due to different rate-control definitions (76.1 versus 83.4 beats per minute). There was no difference in outcome between the patients included in AFFIRM or RACE, though a heart rate >100 beats per minute was associated with a worse outcome. Lenient control was associated with far fewer pacemaker implantations than strict control. Thus, all available data showed no clear benefit of strict rate control as compared with lenient rate control; however, only retrospective data were available. n nHeart rate and quality of life can also be assumed to be related. A higher heart rate could cause more or more severe symptoms than a lower heart rate. However, instituting a stricter rate-control strategy requires more negative dromotropic drugs. Prospective data on quality of life and different rate-control studies were also lacking.