Modulation of cardiac contractility. A potential treatment of heart failure?

Abstract

During the last 10 years, electrical treatment of heart failure (HF) has become more and more popular. Cardiac resynchronization therapy (CRT), alone or combined with defibrillation, has been confirmed to be effective in patients with moderate or severe HF and ventricular dyssynchrony, manifest as a QRS duration >120 ms, though its effectiveness has not been confirmed in patients presenting with HF and a narrow QRS.1 As for all new treatments of HF, the clinical validation of CRT has been slow and occurred in four stages, including (i) limited observational studies to establish its feasibility; (ii) short-term, randomized, crossover studies to validate the clinical concept;2,3 (iii) large, controlled, parallel-design trials with a view to measure the clinical impact of this therapy on major morbidity and mortality;4,5 and (iv) publication of clinical guidelines. It took >10 years after the publication of the first case report6 for professional societies to assign CRT a Class I, evidence level A, indication.7 Borgreffe et al. 8 report the results of a first, crossover, randomized study of large size, which examined the safety and efficacy of cardiac contractility modulation (CCM), a new form of electrical treatment of HF. As in the case of CRT, these are the initial stages of the clinical validation process. CCM is an original and interesting concept, though its mode of action remains obscure.9–12 It is based on the delivery of electrical signals to the myocardium during the absolute refractory period. The ‘non-excitatory’ CCM impulse contains ∼150 times the energy delivered by a conventional pacing pulse. In contrast to paired pacing, or to post-extrasystolic potentiation, CCM pulses do not induce additional action potential. While they do not cause contraction of the myocyte, studies in isolated, superfused, normal papillary muscle suggest that … *Corresponding author: Tel: +33 2 99 28 25 25, Fax: +33 2 99 28 25 10, Email: jean-claude.daubert{at}chu-rennes.fr