title: Cardiac contractility modulation by non-excitatory electrical currents. The new frontier for electrical therapy of heart failure.
abstract: Heart failure (HF) may complicate ischemic heart disease in both its acute and chronic manifestations, representing a prevalent health problem throughout the world. Development of therapies to improve heart function, relieve symptoms, reduce hospitalizations and improve survival is a high priority in cardiovascular medicine. The available pharmacological strategies, including angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists, beta-blockers, and aldosterone receptor antagonists have recently been complemented by new electrical therapy, including implantable cardioverter-defibrillators for "MADIT II" patients and cardiac resynchronization for the 30% of HF patients with concomitant intraventricular conduction delay. The wide variety of available HF medications provides ample evidence that we have not yet succeeded in this effort. Safe and effective inotropic electrical therapy could be a useful addition to our therapeutic armamentarium in an attempt to correct Ca2+ fluxes abnormalities during the cardiac action potential. Cardiac contractility modulation (CCM) by means of non-excitatory electrical currents delivered during the action potential plateau has been shown to acutely enhance systolic function in humans with HF. Herewith, we report on our preliminary experience with CCM therapy for patients with HF, providing fundamental notions to characterize the rationale of this novel form of therapy. Briefly, CCM therapy appears to be safe and feasible. Proarrhythmic effects of this novel therapy seem unlikely. Preliminary data indicate that CCM gradually and significantly improves systolic performance, symptoms and functional status. The technique would appear to be attractive as an additive treatment for severe HF. Controlled randomized studies are needed to validate this novel concept.
authors.affiliation: Department of Cardiology, Electrophysiology and Cardiac Pacing Unit, San Raffaele University Hospital, Milan, Italy. giuseppe.augello@hsr.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Augello
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Santinelli
authors.forename: Gabriele
authors.initials: G
authors.lastname: Vicedomini
authors.forename: Patrizio
authors.initials: P
authors.lastname: Mazzone
authors.forename: Simone
authors.initials: S
authors.lastname: Gulletta
authors.forename: Francesco
authors.initials: F
authors.lastname: Maggi
authors.forename: Yuval
authors.initials: Y
authors.lastname: Mika
authors.forename: GianBattista
authors.initials: G
authors.lastname: Chierchia
authors.forename: Carlo
authors.initials: C
authors.lastname: Pappone
mesh_terms: D000200:Action Potentials / Q000502:physiology; D002306:Cardiac Volume / Q000502:physiology; D004599:Electric Stimulation Therapy; D006333:Heart Failure / Q000503:physiopathology* / Q000628:therapy*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology*; D013318:Stroke Volume / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology