First-in-man Implantation of a Cardiac Microcurrent Device for Chronic Systolic Heart Failure.

Current therapies significantly improve survival and clinical endpoints in patients suffering from chronic heart failure with reduced ejection fraction (HFrEF), but most are not sufficient to reverse adverse remodeling and improve myocardial contractility. Herein, we report the first-in-man experience with a novel fully implantable device for cardiac electrical microcurrent (C-MIC) application. A 79-year-old man suffering from HFrEF (dilated cardiomyopathy, NYHA class III, left ventricular ejection fraction 30%) successfully underwent implantation of the C-MIC device through left anterolateral thoracotomy. At 30-day follow-up, no device-related complications were observed, demonstrating feasibility of C-MIC implantation in a patient suffering from HFrEF.

Cardio-microcurrent device for chronic heart failure: first-in-human clinical study.

AIMS: Most devices for treating ambulatory Class II and III heart failure are linked to electrical pulses. However, a steady electric potential gradient is also necessary for appropriate myocardial performance and may be disturbed by structural heart diseases. We investigated whether chronic application of electrical microcurrent to the heart is feasible and safe and improves cardiac performance. The results of this study should provide guidance for the design of a two-arm, randomized, controlled Phase II trial. METHODS AND RESULTS: This single-arm, non-randomized pilot study involved 10 patients (9 men; mean age, 62 ± 12 years) at two sites with 6 month follow-up. All patients had New York Heart Association (NYHA) Class III heart failure and non-ischaemic dilated cardiomyopathy, with left ventricular ejection fraction (LVEF) <35%. A device was surgically placed to deliver a constant microcurrent to the heart. The following tests were performed at baseline, at hospital discharge, and at six time points during follow-up: determination of LVEF and left ventricular end-diastolic/end-systolic diameter by echocardiography; the 6 min walk test; and assessment of NYHA classification and quality of life (36-Item Short-Form Health Survey questionnaire). Microcurrent application was feasible and safe; no device-related or treatment-related adverse events occurred. During follow-up, rapid and significant signal of efficacy (P < 0.005) was present with improvements in LVEF, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and distance walked. For eight patients, NYHA classification improved from Class III to Class I (for seven, as early as 14 days post-operatively); for one, to Class II; and for one, to Class II/III. 36-Item Short-Form Health Survey questionnaire scores also improved highly significantly. CONCLUSIONS: Chronic application of microcurrent to the heart is feasible and safe and leads to a rapid and lasting improvement in heart function and a near normalization of heart size within days. The NYHA classification and quality of life improve just as rapidly.

Bioelectrical signals improve cardiac function and modify gene expression of extracellular matrix components.

AIMS: Beyond the influence of stimulating devices on cardiac excitation, their use in treating patients with heart failure has positive effects on the myocardium at the molecular level. Electrical signals can induce a wide spectrum of effects in living tissue. Therefore, we sought to determine whether applying electrical microcurrent directly to failing hearts leads to functional improvement. METHODS AND RESULTS: Sixteen male spontaneously hypertensive rats (SHRs) with heart failure underwent application of a patch electrode to the left ventricular epicardium and placement of a subcutaneous counter electrode. The electrode delivered a 0.35 µA microcurrent to nine of the SHRs for 45 ± 3 days; the other seven SHRs were used as controls. At baseline and before the SHRs were humanely put to death, we measured the left ventricular ejection fraction (LVEF) and the thickness of the LV posterior wall during systole and diastole (LVPWs/d). We used quantitative PCR to determine extracellular matrix parameters [collagen I-III, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinases 3 (TIMP3), TIMP4, connexins (Cxs) 40/43/45, transforming growth factor (TGF)-ß, and interleukin (IL)-6]. Among SHRs undergoing microcurrent application, LVEF normalized (mean decrease, 22.8%; P = 0.009), and LVPWs decreased (mean, 35.3%; P = 0.001). Compared with the control group, the SHRs receiving microcurrent exhibited a mean decrease in the gene expression of collagen I (10.6%, P = 0.003), TIMP3 (18.5%, P = 0.005), Cx43 (14.3%, P = 0.003), Cx45 (12.7%, P = 0.020), TGF-ß (13.0%, P = 0.005), and IL-6 (53.7%, P = 0.000). Microcurrent application induced no changes in the expression of collagen III, MMP-2, MMP-9, TIMP4, or Cx40. CONCLUSIONS: Applying microcurrent to the LV epicardium of SHRs leads to statistically significant functional improvement and alterations in the levels of inflammatory and extracellular matrix components.