Itzhak Shemer

Cardiac Contractility Modulation by Electric Currents Applied During the Refractory Period in Patients With Heart Failure Secondary to Ischemic or Idiopathic Dilated Cardiomyopathy

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.

Systems analysis: a systemic analysis of a conceptual model

Adopting an appropriate model for systems analysis, by avoiding a narrow focus on the requirements specification and increasing the use of the systems analysts knowledge base, may lead to better software development and improved system life-cycle management.

Electrical modulation of cardiac contractility: Clinical aspects in congestive heart failure

Heart failure is a highly prevalent disease in western society. Drug therapies aimed at increasing myocardial contractility have been associated with decreased survival. Several short and mid term clinical studies have suggested adjuvant or alternative therapies to congestive heart failure using modified pacing techniques that were aimed to increase contractility (e.g. Paired pacing) or restore synchrony of contraction (biventricular pacing). While delivery of paired pacing was abandoned during the early 70s, biventricular pacing has recently emerged as an adjuvant treatment to limited group of congestive heart failure patients with aberrant left ventricular conduction. In this brief review, we describe our initial safety and efficacy experience in patients with heart failure using a novel non-stimulatory electrical approach to the delivery of positive inotropic therapy to the failing myocardium. The study suggests that unlike modified pacing techniques, delivery of the signal to the left ventricle during the refractory period resulted in a rapid increase in myocardial contractility and improved hemodynamic performance. The near instantaneous contractility improvement achieved by this type of stimulus was shown to be safe and effective independently of the primary cause of heart failure or the function of the conduction system. Unlike pharmacologic treatments, which have a relatively constant effect, use of electrical stimuli may prove useful as a new therapeutic modality in the treatment of heart failure with which contractility can be improved when and as needed.

Global Improvement in Left Ventricular Performance Observed with Cardiac Contractility Modulation is the Result of Changes in Regional Contractility

Cardiac Contractility Modulation (CCM) is a novel therapeutic strategy for increasing myocardial systolic performance. CCM involves nonexcitatory electrical stimulation that can be delivered via standard LV pacing lead approaches (i.e. temporary epicardial electrodes placed during surgery or specialized coronary venous leads presently under development). Unlike other heart failure therapies, CCM is targeted to a very speci®c region of the myocardium, thus avoiding extracardiac side effects and untoward effects related to nonspeci®c cardiac activation. The purpose of this paper is to review experiments performed for the most part in normal, acute experimental preparations, that assess the spatial extent of the CCM effect. These experiments support the hypothesis that the global effects on cardiac systolic function observed during CCM are the direct result of changes in regional contractility close to the CCM site. The implications of this observation, including the possibility of taking advantage of potential regional differences in susceptibility to CCM effect or optimizing therapy by multisite CCM stimulation will also be discussed.