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Cardiac contractility modulation by electric currents applied during the refractory period in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy

https://doi.org/10.1016/S0002-9149(02)02868-0Get rights and content

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/dtmax 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/dtmax 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.

Section snippets

Patient recruitment:

The present study included patients with either ischemic or idiopathic dilated cardiomyopathy and ejection fraction ≤35%, who were referred for an electrophysiologic study or implantation of a pacing device, and who were willing and able to provide written informed consent. Long-term HF medications were maintained at the time of the study, including digoxin, an angiotensin-converting enzyme inhibitor, diuretics, and β blockers. Patients with atrial fibrillation, frequent ventricular premature

Results

Table 1lists demographic and baseline hemodynamic data for the 24 patients enrolled in the study. Etiology of HF was ischemic in 9 patients (37%) and idiopathic in 15 (63%). On average, ejection fraction was 28 ± 6% and New York Heart Association class was 2.7 ± 0.6. As expected, average QRS duration was higher in protocol 3 patients. Indexes of isovolumetric (dP/dtmax) and ejection-phase (pulse pressure) systolic function decreased to a similar degree in patients from all 3 protocols.

Discussion

The present study demonstrated the feasibility of enhancing global LV performance by applying nonexcitatory electric currents to a region of the ventricular myocardium. The CCM signals were shown to induce a 9% increase in dP/dtmax and a 10% increase in aortic pulse pressure during epicardial delivery to the left ventricle. Comparable systolic enhancement was also obtained by applying the CCM current to the RV septum, raising the possibility that direct stimulation of the left ventricle may not

Acknowledgements

We wish to express our appreciation to the patients and to the technicians and nurses of the electrophysiologic and cardiac pacing unit for their dedication and outstanding support.

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    Following TAVI and MitraClip®, many structural intervention devices that correct the structure of the heart and valves have been developed and prepared for clinical application [75,83–85]. Cardiac contractility modulation (CCM), which intervenes in the cardiac stimulation conduction system, has shown clinical benefits for patients with heart failure [86]. Based on the accumulation of knowledge in many basic research fields, autonomic interventions have recently made remarkable progress toward clinical application [75,87–89] (Table 2).

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