We appreciate the letter by Márguez and colleagues and we are thankful for their valuable comments to our paper.1 Recent guidelines2 recommend cardiac resynchronization therapy (CRT) in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) and expected high percentage of ventricular pacing, to decrease the risk of worsening HF. Nonetheless, as correctly noticed by DeSisti et al.3 in their previous work, an LVEF cut-off value has not yet been defined. They also noticed that chronic right ventricular pacing can induce a reduction in LVEF of 5–10% points, and therefore suggested an LVEF cut-off value of 40–45% as criterion for the CRT device if permanent ventricular pacing is expected.
In our study, we found that LVEF < 50% was the independent predictor of new-onset HF over medium-term follow-up, and thus we suggested that CRT could play a preventive role in these patients.
A priori, we adopted the 50% LVEF value because the LVEF range 35–50% is usually considered an area of mild systolic dysfunction. However, in our opinion, adopting a single cut-off value may be inadequate when dealing with an echocardiographic parameter like LVEF, that is known to be affected by large intra- and inter-observer variability, and to be extremely variable, spontaneously and in response to therapies. Actually, DeSisti and colleagues themselves properly reported an LVEF range between 40 and 45%, instead of a single value.
In general, CRT implantation may be worthwhile in patients with mild HF and a bradycardia indication for pacing, but the benefits should be weighed against the added complication rate of CRT devices, as shown in the BLOCK-HF trial.4 On the other hand, although a strategy of initially conventional anti-brady pacing, with later upgrade in case of worsening symptoms is considered reasonable in the current guidelines,2 the upgrade to CRT is not free from complications and this should not be neglected.
The results of the ongoing BIOPACE trial (ClinicalTrials.gov Identifier: NCT00187278) will provide further evidence of the potential benefits of CRT in patients in whom ventricular pacing cannot be avoided. At the same time, the MIRACLE-EF trial (ClinicalTrials.gov Identifier: NCT01735916) is testing the efficacy of CRT in patients with LVEF in the range of 36–50%, left bundle branch block and no need for cardiac pacing. At last, for patients with an intermittent or minimal need for pacing, the use of algorithms that favour atrial pacing over atrioventricular sequential pacing is standard. However, as noticed by DeSisti et al.,3 in patients with prolonged PR interval this strategy was demonstrated to present increased HF and mortality. Indeed, a prolonged PR interval is a clinically relevant marker for atrioventricular dyssynchrony, which adversely influences cardiac mechanics. Therefore, maintaining atrioventricular synchrony may be important, and the synergistic effect of atrioventricular and inter-ventricular synchronization offered by CRT could provide benefits also in these patients. This is investigated in the ongoing REAL-CRT study (ClinicalTrials.gov Registration in progress). The results of all these studies are awaited to clarify the potential role of CRT in the treatment of mild systolic dysfunction.
Conflict of interest: U.R., C.C., and S.V. are employees of Boston Scientific, Inc. The other authors have no conflicts of interest to declare.