title: Cardiac contractility modulation by electric currents applied during the refractory period in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.
abstract: We assessed the feasibility of cardiac contractility modulation (CCM) by electric currents applied during the refractory period in patients with heart failure (HF). Extracellular electric currents modulating action potential and calcium transients have been shown to potentiate myocardial contractility in vitro and in animal models of chronic HF. CCM signals were biphasic square-wave pulses with adjustable amplitude, duration, and time delay from sensing of local electric activity. Signals were applied to the left ventricle through an epicardial vein (in 12 patients) or to the right ventricular (RV) aspect of the septum endocardially (in 6 patients). Simultaneous left ventricular (LV) and aortic pressure measurements were performed using a Millar catheter (Millar Instruments, Houston, Texas). Hemodynamics during RV temporary dual-chamber pacing was regarded as the control condition. Both LV and RV CCM stimulation increased dP/dt(max) to a similar degree (9.1 +/- 4.5% and 7.1 +/- 0.8%, respectively; p <0.01 vs controls), with associated aortic pulse pressure changes of 10.3 +/- 7.2% and 10.8 +/- 1.1% (p <0.01 vs controls). Regional systolic wall motion assessed quantitatively by color kinesis echocardiography was markedly enhanced near the CCM electrode, and the area of increased contractility involved 4.6 +/- 1.2 segments per patient. In 6 patients with HF with left bundle branch block, CCM signals delivered during biventricular pacing (BVP) produced an additional 16.1 +/- 3.7% increase in dP/dt(max) and a 17.0 +/- 7.5% increase in pulse pressure compared with BVP alone (p <0.01). CCM stimulation in patients with HF enhanced regional and global measures of LV systolic function, regardless of the varied delivery chamber or whether modulation was performed during RV pacing or BVP.
authors.affiliation: Department of Cardiology, San Raffaele University Hospital, Milan, Italy. carlo.pappone@hsr.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Pappone
authors.forename: Salvatore
authors.initials: S
authors.lastname: Rosanio
authors.forename: Daniel
authors.initials: D
authors.lastname: Burkhoff
authors.forename: Yuval
authors.initials: Y
authors.lastname: Mika
authors.forename: Gabriele
authors.initials: G
authors.lastname: Vicedomini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Augello
authors.forename: Itzhak
authors.initials: I
authors.lastname: Shemer
authors.forename: David
authors.initials: D
authors.lastname: Prutchi
authors.forename: Walid
authors.initials: W
authors.lastname: Haddad
authors.forename: Ricardo
authors.initials: R
authors.lastname: Aviv
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Snir
authors.forename: Itzhak
authors.initials: I
authors.lastname: Kronzon
authors.forename: Ottavio
authors.initials: O
authors.lastname: Alfieri
authors.forename: Shlomo A
authors.initials: SA
authors.lastname: Ben-Haim
mesh_terms: D001011:Aorta / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D002037:Bundle-Branch Block / Q000503:physiopathology; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000503:physiopathology*; D018618:Echocardiography, Doppler, Color; D004553:Electric Conductivity; D004558:Electric Stimulation / Q000379:methods; D004562:Electrocardiography; D004566:Electrodes; D022062:Electrophysiologic Techniques, Cardiac / Q000379:methods*; D005240:Feasibility Studies; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology*; D013318:Stroke Volume / Q000502:physiology; D016276:Ventricular Function; D016277:Ventricular Function, Left / Q000502:physiology*