Performance of the Cardiac Microcurrent (C-MIC) System With a Less Invasively Placed Left Ventricular Lead

Pilot Study to Investigate the Performance of the Cardiac Microcurrent (C-MIC) System With a Less Invasively Placed Left Ventricular Lead

Patients with idiopathic dilated cardiomyopathy in heart failure (NYHA class III - IV) with a baseline left ventricular ejection fraction between ≥25% and ≤35%, and patients with non-ischemic cardiomyopathy in heart failure (NYHA class III-IV) with a baseline left ventricular ejection fraction >40% and <50% despite guideline-directed medical therapy, will receive C-MIC treatment in addition to optimal medical management.

The device can be implanted without the need for open-heart surgery. Patients are assigned to one of two groups according to the indications under investigation. At the end of the study after 6 months, the C-MIC System will be turned off. The primary endpoint of the study is the absolute change in left ventricular ejection fraction after 6 months of treatment.

Target patients for the C-MIC System include: (1) patients with idiopathic dilated cardiomyopathy who have systolic left ventricular dysfunction (NYHA class III-IV) despite adequate heart failure therapy and a left ventricular ejection fraction between 25% and 35%, and (2) patients with non-ischemic cardiomyopathy who have systolic left ventricular dysfunction (NYHA class III-IV) despite adequate heart failure therapy and a left ventricular ejection fraction >40% and <50%. All patients must have a documented history of heart failure for more than 1 year but less than 5 years.

In previous studies, C-MIC was successfully implanted with one of the electrodes (the LV patch electrode) being placed directly on the heart. This study uses a less invasive technique to place the LV patch electrode, eliminating the need for a thoracotomy.

In all the groups, the effect of the microcurrent therapy will be assessed by comparing LV ejection fraction changes between baseline and after 6 months of microcurrent treatment (primary endpoint).

Inclusion Criteria Idiopathic Dilated Cardiomyopathy with HFrEF:

1. Patients with idiopathic dilated cardiomyopathy who have systolic left ventricular dysfunction despite adequate therapy of heart failure (NYHA III - IV).
2. Patients who have a baseline left ventricular ejection fraction of ≥25% and ≤35% assessed by corelab.

Inclusion Criteria Non-Ischaemic Cardiomyopathy with HFmrEF:

1. Patients with non-ischemic cardiomyopathy with mildly reduced left ventricular ejection fraction despite adequate therapy of heart failure (NYHA III - IV).

2. Patients who have a baseline left ventricular ejection fraction of >40% and <50% assessed by corelab.

   Inclusion Criteria for all Patients:

3. Patients with symptomatic chronic heart failure for more than 1 year and less than 5 years at screening based on the date of diagnosis.

4. Female and male patients aged ≥18 years - 75 years.

5. Patient who understands the nature of the procedure and on-going device therapy. Patient is informed about their participation in a chronic clinical trial and about the intended treatment period of 6 months which is derived by the fact that according to current knowledge microcurrent treatment exceeding 6 months will not have additional favorable effects which means it will not further improve cardiac function. Furthermore, the patient is informed about the possibility of device explantation, informed regarding possible risks and is able to give written informed consent prior to any procedures and is considered willing and able to adhere to the study regimen and to return for all follow-up visits.

6. Patients receiving appropriate, stable guideline directed medical therapy for heart failure at least for the 3 months prior to screening. Stable is defined as no more than a 50% increase or 50% decrease in dose. If the patient is intolerant of guideline recommended doses of heart failure medication, documented evidence must be available.

   Guideline directed medical therapy includes for:

   • Patients with HFrEF:

   - Angiotensin-converting enzyme inhibitor (ACE-I) or

   - Angiotensin receptor-neprilysin inhibitor (ARNI)

   - Beta-blocker

   - Mineralocorticoid receptor antagonist (MRA)

   - Dapagliflozin/Empagliflozin inhibitor (SGLT2i)

   • Patients with HFmrEF - Diuretics (if symptomatic)

     • Dapagliflozin/Empagliflozin inhibitor (SGLT2i)

7. Patients who can perform a non-assisted 6-minute walk test.

8. Patients must have a body mass index within the range of 20 - 36 kg/m².

9. Informed consent in writing obtained from patient.

Exclusion Criteria:

Patients who are not likely to experience improvement of their chronic heart failure by the microcurrent therapy, because the causes of the disease cannot be influenced even if the patients fulfill the indication for use of the device or if the therapy with the C-MIC System is not possible or might be associated with unknown risks:

1. Patients who have a potentially correctible cause of heart failure, such as valvular heart disease or congenital heart disease.

2. Patients with an indication for a CRT system according to current guidelines.

3. Patients who have been hospitalized for heart failure which required the use of inotropic support within 30 days before screening.

4. Patients with systolic blood pressure above 150 mmHg and diastolic blood pressure above 90 mmHg despite optimal antihypertensive medical treatment.

5. Patients with hemoglobin blood level < 12 g/dl in male and < 10 g/dl in female patients.

6. Patients with primary pulmonary hypertension

7. Patients who have genetic connective tissue disease (for example Marfan syndrome).

8. Patients with a prosthetic tricuspid valve.

9. Patients in whom access for implantation of the leads cannot be obtained (i.e. known venous occlusion, post radiation therapy).

10. Patient with other features (i.e. thorax deformity) that in the eyes of the investigator make the straightforward placement of the device seem unlikely.

11. Patients with a pacemaker, an ICD system, a CRT system or with a CCM system.

12. Current pregnancy or

13. Breastfeeding/lactating women

14. Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception (e.g. intrauterine device, oral contraceptives, barrier methods, or other contraception deemed adequate by the investigator) 2 months before and until 1 month after C-MIC therapy.

    Women are considered post-menopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 2 months before screening.

15. Patients whose exercise tolerance is limited by a condition other than heart failure (e.g. chronic obstructive pulmonary disease, peripheral vascular 16.

Patients on immunosuppressive therapy. 17.Patie nts with present malignancy. 18. Patients with an active infection considered by the investigator to be unsafe for the patient's participation in the study.

19. Patients with renal dysfunction (i.e., estimated glomerular filtration rate <45 mL/min /1,73 m²). Use the "CKD-EPI Creatinine Equation (2021)" as found on https://www.kidney.org/professionals/gfr\_calculator.

20. Patients with history or presence of relevant liver diseases or hepatic dysfunction as indicated by abnormal liver function tests at screening and baseline: ALT (SGPT), AST (SGOT), γ-GT, alkaline, phosphatase and serum bilirubin > 2 × upper limit of normal (ULN). Increase of these liver enzymes caused by cardiac disorders in the absence of other possible causes of liver damage are not meant by this.

21. Patients with a history of drug or alcohol abuse within the 12 months prior to screening.

22. Patients who, in the opinion of the Principal Investigator, are unlikely to comply with the protocol requirements, instructions and trial related restrictions, e.g., uncooperative attitude, inability to return for follow-up visits, psychological illness, and improbability of completing the trial.

23. Participation in any study of an investigational device or drug within 90 days prior to planned study.

24. Vulnerable Patients (e.g. patients requiring a legal representative, patients kept in detention, any service within the army, and employees of the sponsor or at an investigator site).

25. Patients who are not able to avoid the following areas (i.e. due to work):

• Areas with strong magnetic fields
• Areas with strong external electrical influences
• Areas with a warning notice "Access prohibited for pacemaker patients" or similar.
• Areas with high temperatures