Current practice of cardiac resynchronization therapy (CRT) in the real world: insights from the European CRT survey

Large randomized controlled trials have demonstrated that cardiac resynchronization therapy (CRT) improves morbidity and mortality in patients with moderate to severe heart failure [New York Heart Association (NYHA) functional class III–IV], reduced left ventricular ejection fraction (LVEF ≤35%), and a broad QRS complex >120 ms on optimal medical therapy.1–3 As a result, the impressive survival benefit as well as the improvement in heart failure symptoms and quality of life observed in these trials have spurred interest in extending resynchronization therapy to a larger number of heart failure patients. Indeed, several lines of evidence indicate that currently employed guidelines (mainly based on the selection criteria used in the aforementioned pivotal trials) may not be perfect at identifying patients most likely to benefit from CRT, with a significant proportion of patients being ‘non-responders’ based on clinical outcomes or echocardiographic remodelling.4 Conversely, results from various small studies imply that certain patient populations may benefit from CRT despite the fact that they do not fulfil the criteria of current CRT guidelines.5–7 In the absence of randomized trials, data from large-scale ‘real world’ surveys provide a unique opportunity to study both the current practice regarding the employment of a novel type of therapy as well as its efficacy and safety, including ‘off-label’ indications. The European CRT Survey, a joint initiative by the Heart Failure Association (HFA) and the European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC), reports on the current European practice in the use of CRT.8 In order to provide this information, 2438 patients from 141 centres in 13 European countries who underwent successful implantation of a CRT device were followed from November 2008 until June 2009. In addition to providing a detailed description of patient demographics, selection criteria, and periprocedural outcomes, the survey's data were further dissected according to the implanted device and age of the recipients. The authors found that patients receiving CRT-P [i.e. a biventricular pacing device without implantable cardioverter–defibrillator (ICD) function] were older, less likely to present with co-morbidities including ischaemic heart disease or diabetes mellitus, and had better left ventricular function as compared with those receiving a CRT-D (i.e. CRT + ICD) device. Furthermore, the data demonstrate that patients older than 75 years more frequently had atrial fibrillation, a longer QRS duration, or concomitant co-morbidities (as reflected by higher serum creatinine and B-type natriuretic peptide (BNP) levels] as compared with those younger than 75 years. Probably as a result of the latter (and possibly for socioeconomic reasons), older patients were more likely to receive CRT-P devices. While most of these associations do not necessarily come as a surprise and are in good agreement with previous trials and clinical experience, the survey does also show some interesting aspects of cardiac resynchronization practice across Europe which deserve further attention. Most interestingly, a substantial number of patients received CRT devices for ‘off-label’ indications, including 9% of patients with a narrow QRS complex (<120 ms) as well as 10% with a QRS duration between 120 and 129 ms. Currently available data regarding the benefit of CRT in heart failure patients with a narrow QRS complex are conflicting. Using echocardiography-based dyssynchrony criteria, several small single-centre studies were able to identify patients with a narrow QRS who responded favourably to CRT.5,6,9 In contrast, the results of two recent randomized pilot studies (RethinQ10 and ESTEEM-CRT) remained elusive due to several inherent limitations.11 Eventually, the answer to whether CRT improves morbidity and mortality in this particular patient group can only be provided by an adequately powered, endpoint-driven randomized clinical trial, which is currently underway (Echocardiography Guided Cardiac Resynchronization Therapy—EchoCRT; NCT00683696, www.clinicaltrials.gov).11 Before the results of this trial become available, it will be of interest to observe the direction in which the expected 1 year data from the survey by Dickstein et al.8 will be pointing. Unfortunately, only qualitative assessment instead of quantitative (echocardiographic) parameters of left ventricular dyssynchrony were registered for these patients, which will make further comprehensive analysis of this subgroup's outcome difficult. Previous small trials have, moreover, indicated that patients with atrial fibrillation may profit from CRT,7 but evidence from large trials is lacking as this particular patient group was generally excluded. Controversy currently exists, however, regarding the necessity of AV nodal ablation, of ablation of atrial fibrillation itself, concomitant rate- or rhythm-controlling medication, and optimal device programming. In the survey by Dickstein et al., 8 23% of patients implanted were in atrial fibrillation. In view of the large proportion of heart failure patients with atrial fibrillation in clinical practice and the fact that data from large trials are scarce, further information on these parameters would have been desirable for this interesting subgroup. Nevertheless, outcome data after 1 year (possibly including this interesting information) will demonstrate to what extent these patients benefit in terms of clinical and echocardiographic improvement. Evidence is emerging that patients with mildly symptomatic heart failure (i.e. NYHA class

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