Published in UAB Insight, Winter 2007
Clinical trial underway
A new implantable device uses cardiac contractility modulation (CCM) to improve systolic function in patients with heart failure. CCM — manipulation of cellular calcium by electrical impulses — augments ionic calcium movement in and out of cells, enhancing contractility and cardiac performance.
“This is potentially one of the most important therapies on the horizon for patients with congestive heart failure,” says cardiologist Jose A. Tallaj, MD, the principal investigator for the UAB site of a national, randomized clinical trial evaluating the safety and effectiveness of the implant, called Optimizer™ III.
Weakening heart contractility partially results from a reduction in cellular calcium that activates myofilaments during each beat. Pacemaker-like leads — one in the right atrium that senses atrial activation and two on the right ventricular septum — deliver nonexcitatory electrical signals during the absolute refractory period. The impulses stimulate calcium release into the cell, both from the extracellular space and from the sarcoplasmic reticulum. The heart responds with a stronger contraction, and as calcium moves back inside the sarcoplasmic reticulum, the heart relaxes.
“Available data from previous animal studies and limited human implantation are encouraging in terms of adverse remodeling, hemodynamics, and symptoms. The device’s use of a natural mechanism to augment cardiac contraction increases the benefits of modern heart failure therapy,” Tallaj says.
Heart failure medications provide a survival benefit and relief of some symptoms, but most patients are still markedly impaired and disabled. Optimizer III’s CCM therapy improves quality of life measures and functional capacity, Tallaj says. The device may be especially suited to New York Heart Association (NYHA) class III and IV patients who remain symptomatic on medical therapy or cannot tolerate additional uptitration of their medical regimen.
“This implant can provide relief of symptoms for heart failure patients who are short of breath during daily activities such as walking around the house, taking a bath, or going grocery shopping,” he says.
Ongoing Research
Tallaj implanted his first device at UAB in April 2006 with excellent results. Researchers aim to recruit as many as 418 patients from 50 sites for the 13-month trial sponsored by the manufacturer, Impulse Dynamics (USA). Candidates are patients aged ≥19 years with an ejection fraction of ≤35%. They must be designated NYHA class III or IV with congestive heart failure and on optimal medical therapy for at least 90 days.
Primary outcome measures 6 months after implantation include exercise tolerance (evaluated with a 6-minute walk test), improvement in NYHA class, quality of life, and objective measurements.
Tallaj says previous animal studies showed an increase in acute heart muscle strength with the device and in some cases indicated long-lasting results up to a year. Possibilities for the Optimizer III as a heart failure treatment may entail combination therapy using CCM in conjunction with pacemakers and defibrillators. “Of course, in the future we hope an integrated device can improve survival in patients with chronic heart failure as well as provide a better quality of life.”
For more information
Dr. Jose Tallaj
1.800.UAB.MIST
mist@uabmc.edu