Cause of death and CRT device selection: striving for certitude?

Implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy (CRT) devices have had a significant favourable impact on hospitalization and mortality among patients with heart failure (HF). Despite some degree of overlap, the therapeutic rationales for these two forms of device-based therapies are distinct, where ICDs abort arrhythmic death and CRT devices improve cardiac function. The efficacy of ICDs and CRT has been clearly established after large-scale randomized controlled trials (RCTs). 4 However, as with most invasive therapies, there is a constant quest to minimize harm while enhancing the value of the care being delivered. Notably, the majority of patients who are candidates for CRT are also eligible for an ICD by virtue of low left ventricular ejection fraction (LVEF). If only ICDs were totally benign and an inexpensive add-on, this difference might not have been clinically significant. Inappropriate shock therapy from ICDs has been associated with higher mortality, and therefore the relative benefit of adding defibrillator therapy to CRT (i.e. CRT-D), particularly in patients whose highest risk of dying is from pump failure, has been questioned. The only large RCT which compared CRT-D and pacemaker CRT (CRT-P) vs. optimal medical therapy (COMPANION), was not powered to examine differences in mortality between these two arms of device therapy. The median age of enrolled patients was 69 years, of which the majority was New York Heart Association (NYHA) class III (86%) and the remaining ambulatory class IV. Cardiac death was reduced in CRT-D patients as compared with optimal pharmacologic therapy (P 1⁄4 0.006) driven by a significant reduction in sudden cardiac death (SCD). No difference was found between non-cardiac deaths in patients with CRT-D, CRT-P or medical therapy. CRT-P was associated with a non-significant trend towards reduced pump failure deaths and overall cardiac deaths. In part, it was due to this ‘lingering uncertainty’ regarding the role of CRT-P in addressing survival that the results of the Cardiac Resynchronization in Heart Failure (CARE-HF) trial came as a welcome relief one year later, convincingly demonstrating a 36% relative risk (RR) reduction for death with CRT-P vs. medical therapy. Anecdotal reports of CRT-induced proarrhythmia have caused some degree of concern for the potential risk of innate and induced SCD in this cohort of CRT-P patients. Longer-term data from CARE-HF, however, have shown that improved pump function from CRT-P can actually halve the risk of SCD. Nevertheless, in the absence of an RCT with a head-to-head comparison of CRT-D vs. CRT-P, there is a lack of consensus regarding the choice of device and consequently there remains considerable variability in practice. In addition, there is also little comparative data on the mode of death between these two cohorts of patients. In this issue of the European Heart Journal, Marijon et al. present results from the CeRtiTuDe registry, analysing causes of death after CRT therapy. Enrolling patients in 41 centres across France between January 2008 and December 2010, CRT implantation and choice of therapy (CRT-D or CRT-P) was left to the discretion of the treating physician based on the 2007 or 2010 update of the Guidelines of the European Society of Cardiology and European Heart Rhythm Association. Patients were followed at 6-month intervals for 2 years by the implanting centre until the close of the study on 1 January 2013. A standardized form was used to record major clinical events, and vital status was ascertained through use of national registries. Causes of death were pre-specified for data collection in CeRtiTuDe. Sudden death was defined as occurring within 1 hour of symptoms in the absence of cardiac deterioration, unexpected death during sleep, or unexpectedly dying within 24 h of last being seen alive. Importantly, fatal arrhythmias associated with end-stage heart failure were classified as non-sudden deaths. Other cardiovascular deaths included myocardial infarction (MI), HF, acute aortic