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The benefits of cardiac resynchronisation therapy (CRT) on long term survival and left ventricular (LV) function of patients with heart failure symptoms have been demonstrated in several randomised controlled trials (RCTs).1–4 w1–w4 The data from those trials form the basis of current recommendations for CRT use.5 ,6 w5 w6 However, several subpopulations, such as elderly patients, diabetics, and patients with atrial fibrillation (AF), non-left bundle branch block QRS morphology or congenital heart disease, are underrepresented in randomised clinical trials, and the effects of CRT remain unclear. For example, the mean age of patients included in the majority of RCTs was <75 years, whereas in the European CRT survey 31% of patients were older than 75 years.7 Similarly, AF was an exclusion criterion in many RCTs, while 31% of patients included in the Medicare Implantable Cardioverter-Defibrillator Registry had AF.8 Table 1 summarises the frequency of specific subpopulations included in RCTs and recent registries.1–3 ,7 ,8 w1–w4 The present article provides an overview of the effects of CRT in subpopulations underrepresented in RCTs and underscores the unmet needs for evidence based treatment in these subpopulations.
NYHA functional class I
After the demonstrated improved outcomes of patients with New York Heart Association (NYHA) functional class III–IV heart failure symptoms treated with CRT, the concept of halting the progression of heart failure in mildly symptomatic patients was the hypothesis of the MIRACLE implantable cardioverter defibrillator (ICD) II, REVERSE, MADIT-CRT, and RAFT trials.3 w3 w4 w7 A meta-analysis pooling data from six randomised trials that included 4572 mildly symptomatic heart failure patients demonstrated that CRT reduced the risk of all-cause mortality (relative risk 0.83, 95% CI 0.72 to 0.96).9 However, among the studies …