Figure 1: The Optimizer Smart Mini System comprises a pulse generator (top left) connected to sensing and pacing leads in the right ventricle septal wall.
In the context of the ongoing AIM HIGHer clinical trial, electrophysiologists at Penn Medicine are performing cardiac contractility modulation, or CCM, device implantation in individuals with heart failure with preserved ejection fraction (HFpEF).
CCM is a method of enhancing cardiac contractility by delivering electrical signals to the left ventricle via standard pacing electrodes implanted in the right ventricular septum; CCM is administered during the absolute refractory period 30–40 ms after detection of local electrical activity. The energy of CCM signals can be delivered at approximately 100 times that of a standard pacemaker without actually stimulating the ventricle. The device signal delivery is synchronized with the detected local electrical activity to increase cardiac output and contractility of cardiac muscle. Over time this has been shown to reverse fetal genes associated with heart failure.
HFpEF now affects as much as 50% of the population with heart failure (HF), a population with few therapeutic options. Although the ejection fraction parameters for HFpEF have been variously defined, according to the American Heart Association, the organization now considers EF>50% to be the threshold for HFpEF. [1] Patients must also have evidence of cardiac dysfunction as the cause of symptoms (eg, abnormal LV filling pattern and elevated filling pressures).
CCM therapy is FDA-approved for HF patients with reduced ejection fraction (HFrEF; <40%), having demonstrated efficacy in this population in early clinical trials. In a later iteration of one of these studies, FIX-HF-5C2, the upper range of EF was extended to 45%, suggesting the possibility of benefit for CCM in individuals with HFpEF. [2]
AIM HIGHer [NCT05064709], a clinical trial initiated to evaluate this finding, is currently underway at Penn Medicine. A multicenter, multi-national, randomized, quadruple-blind, sham controlled trial, AIM HIGHer will evaluate the efficacy and safety of CCM therapy via the Optimizer Smart Mini System (Impulse Dynamics, Marlton, NJ). One of the principal investigators at Penn Medicine for the trial is Benjamin D’Souza, MD, of Penn Cardiology.
The Optimizer is a medical device comprising a subcutaneous pulse generator linked to two cardiac leads (see Figure 1). These wires are connected to electrodes that monitor the electrical activity of the heart to ascertain the specific time during each heartbeat to administer pulses. The Optimizer is powered by a rechargeable battery.
All eligible subjects will be implanted with the Optimizer System, but the device will not be turned on among subjects in the sham arm until the conclusion of the 18 month study.
AIM HIGHer has two continuous parts. The primary efficacy endpoints of Part 1 include a demonstration of improved functional capacity and health status in subjects with symptomatic heart failure with LVEF ≥40% and ≤60% receiving CCM therapy. The Part 1 safety endpoint involves an assessment of the incidence of Optimizer device- or procedure-related complications within the first 12 months after implantation.
The Part 2 efficacy endpoint will assess the safety and effectiveness of CCM therapy in the study population on the basis of clinical outcome data at 18 months.
AIM HIGHer is now open for enrollment at Penn Medicine. For information, please contact Katie Shoemaker at Katie.Shoemaker@pennmedicine.upenn.edu, or Emily Marvel at Emily.Marvel@pennmedicine.upenn.edu.
References
- Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation 2022;145:e895–e1032.
- Wiegn P, Chan R, Jost C, et al. Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-Lead Optimizer Smart SystemThe FIX-HF-5C2 Study. Circulation: Heart Failure 2020;13. FIX-HF-5C2 Study.
About Cardiovascular Clinical Trials at Penn Medicine
In collaboration with the Perelman School of Medicine and its partner institutions, the Penn Heart and Vascular Center, comprising 20 separate programs and divisions, is an internationally recognized leader in basic and translational clinical research. The object of cardiovascular clinical research at Penn Medicine is to achieve the transformation of basic research discoveries into breakthrough diagnostics, therapies and clinical devices for cardiovascular disease, the leading killer in the United States.
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AIM HIGHer Study Access
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Heart and Vascular Pavilion, 3rd Floor
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Philadelphia, PA 19104