First in Human Study of the Icoms Flowmaker

A Prospective, Single Arm, Multicentric, First in Human Study to Evaluate the Safety and Performance at 30 Days of the FineHeart Icoms® FlowMaker® in Subjects With Advanced Heart Failure.

The Icoms® FlowMaker® is a cardiac assist system in the true sense of the word. As assisting means to help or rescue, its function is providing assistance to the heart, which will continue to have its own hemodynamic pump function. The effect of the Icoms® FlowMaker® is to add an additional quantity of blood flow on top of the native blood flow, during each systole. The heart continues to have its own contribution, but a more satisfactory blood flow is restored by the complementary action of the Icoms® FlowMaker® This study is a first in human test to evaluate the safety and the performance of the Icoms Flowmaker. The study population consists of patients with severe heart failure who are at high risk for a conventional LVAD and at high risk for a percutaneous driveline. Ten patients will be recruited and implanted In France , Slovenia and Czech republic.

The study objectives are:

o evaluate the safety and performance of the Icoms® FlowMaker® implantable device in patients with severe heart failure resistant to optimal medical therapy.

--Primary Objective: Assess safety and performance of the device at 30 days post-implantation.

Secondary Objectives: Evaluate the patient's hemodynamic and clinical status, and the device's functionality per technical specifications.

The role of mechanical circulatory support (MCS) in the current landscape of heart failure (HF) therapies can only be appreciated by knowing the potential number of candidates for advanced HF treatment. HF prevalence is 2.6% in the over 300 million US population. Approximately half of all patients with HF have reduced, versus preserved ejection fraction (3.5 million). Only 10-15% of those belong to the New York Heart Association (NYHA) class IIIB-IV.

These data suggest that there are as many as 500,000 patients in whom either LVAD or cardiac transplantation could be indicated following current national guidelines.. However, taking into account important limitations based on age, comorbidities, social and financial constraints, the actual number might be less, but nevertheless 125,000 to 250,000 patients remain as potential candidates for this advanced therapy. The INTERMACS Class 4-7 . population presents an incidence of at least 100,000 patients per year in the USA, Canada and Europe. The main indications for the use of implantable LVADs in patients with end-stage HF are either as a bridge to candidacy (BTC), or as long-term option for those who do not qualify for cardiac transplantation, previously referred to as destination therapy (DT). Only 7.000 to 9.000 MCS devices are implanted worldwide every year, which represents a significant lack of treatment in such sick and mostly not elderly patients.

Consequently, there is a huge discrepancy between the need for MCS treatment (up to 250,000 patients) and the real proportion of patients implanted, due to known, much feared current LVAD-induced complications.

Yet, the greatest increase in LVAD volume has not been in those considered candidates for bridge to heart transplantation (BTT) but for DT, which requires technical improvements to expand MCS devices implants in less severe patients.5-6. The overall survival with LVAD therapy is ≈ 80% at 1 year, and 60% at 5 years, with survival for DT indication lower than other indications at all time points, because of higher incidence of comorbidities and LVAD complications . Presently, the use of the terms BTT or DT to define the indication for LVAD implantation is being replaced by whether the support is intended for temporary or chronic use10.

The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database now includes 25,000 patients:

• 97% benefit from a non-physiological continuous-flow VAD
• The average age at implant is 57 years and 80% are male.
• Overall, 1- and 2-year survival is 80% and 70%, respectively.
• Most implanted patients are INTERMACS Class 1-3 (80-85%).
• Patients with ambulatory HF still account for only 16% of durable device implants to date, due to the fear for LVAD-induced complications.
• Today, nearly 41% are implanted with an intent for long-term DT.
• With the HeartMate 3, neither survival rate, nor infection rate did improve compared to the Intermacs registry cohort only thrombosis and disabling stroke were significantly reduced at 2-year follow-up.

All these precious epidemiological data highlight the crucial need for a new type of MCS device, being more physiological and pulsatile, without a percutaneous driveline (i.e. "fully implantable"). It needs to be easier to implant and/or replace, with less invasive surgery without CPB and thus, finally able to address the most important population of severe HF patients.

Inclusion Criteria:

• 1- Age 18 and 80 years included.
• 2- Written inform consent.
• 3- Females of child-bearing age must agree to use adequate contraception.
• 4- Suitable neurocognitive status.
• 5- Distance between the aortic valve and the LV endocardial apex ≥ 95mm and the Left Ventricular (LV) volume > 200 mL
• 6- Body Surface Area (BSA) ≥ 1.2 m².
• 7- LVEF ≤ 35 % and assessed Intermacs ≤ 4
• 8- Advanced heart failure patients symptomatic despite optimal medical management (OMM) based on the European Cardiology Society guidelines15 otherwise meeting standard best practice indications for implantable LVAD

AND fulfilling at least one of the following criteria approved by the International multidisciplinary expert selection committee:

• 9- Contraindication or excessively heightened risk of a conventional LVAD implant due to factors such as:

• CVP/PCWP ≤ 0.6
• anatomical or surgical factors constituting excessive
• perioperative implant risks.
• (Duly recorded in the source document during the patient Inform
• consent process)

OR

• 10- Patient with high risk of percutaneous driveline-induced morbidity such as:

  • patient with recurrent infections / severe diabetes mellitus / immunodeficiency / cachexia
  • psychological factors limiting percutaneous driveline
  • acceptance and / or management duly recorded in the Psychological evaluation report at screening.

• 11- Temporary ineligibility to heart transplant(active or remission of cancer / highly sensitized PRA…) Duly recorded in the source document during the patient Inform consent process.

• 12- Patient's affiliation to health care insurance, if local requirement

• 13- Patient implanted with a cardioverter defibrillator from Medtronic and Boston or patient requiring implantation of a cardiac defibrillator due to a risk of ventricular arrhythmia

Exclusion Criteria:

• 1-Body Mass Index (BMI) > 40.
• 2- TAPSE ≤10 mm
• 3- Pulmonary VTI ≤ 6cm
• 4- Patients not eligible to transplant due to surgical risks
• 5- Existence of any ongoing mechanical circulatory support (MCS) other than an intra-aortic balloon pump (IABP)
• 6- History of left thoracotomy.
• 7- History of confirmed untreated abdominal or thoracic aortic aneurysm > 5 cm.
• 8- Cardiothoracic surgery within 30 days of implant.
• 9- Acute myocardial infarction within 14 days of implant.
• 10- On ventilator support for > 72 hours within the four days immediately prior to implant.
• 11- Pulmonary embolus within three weeks of implant.
• 12- Presence of current atrial or ventricular thrombus, confirmed by MRI, CT-SCAN or Trans-Esophageal Echocardiography.
• 13- Symptomatic cerebrovascular disease, stroke within 180 days of screening or > 80% stenosis of carotid, vertebral or cranial vessels.
• 14- Moderate to severe aortic regurgitation, defined as > 50% regurgitant fraction.
• 15- Moderate - Severe aortic stenosis, defined as an aortic valve area (AVA) ≤ 1.5 cm2.
• 16- Active, uncontrolled infections, history of hyperleukocytosis with Leucocytes > 10.000/mm3, CRP 17- 10mg/l, PCT > 0,2ng/ml, positive hemocultures < 48 hours, positive urine cultures, positive sputum cultures, any abnormalities identified by CT scan of brain-thorax and abdomino-pelvic region.
• 17- Uncorrected thrombocytopenia or generalized coagulopathy (e.g., platelet count < 100,000 / INR > 2.0 in the absence of anticoagulation therapy).
• 18- Hepatic insufficiency: a total bilirubin > 3 mg/dL within 72 hours before implant, or biopsy proven liver cirrhosis or portal hypertension.
• 19- Pulmonary vascular resistance (PVR) demonstrated to be unresponsive to pharmacological manipulation and the PVR > 6 Wood units.
• 20- Patients with a mechanical heart valve.
• 21- Etiology of heart failure due to, or associated with, uncorrected thyroid disease, obstructive cardiomyopathy, pericardial disease, amyloidosis, active myocarditis, or restrictive cardiomyopathy, ventricular septal defect
• 22- History of severe Chronic Obstructive Pulmonary Disease (COPD) or severe restrictive lung disease. GOLD (Global Initiative for Chronic Obstructive Lung Disease) score < 3.
• 23- Participation in any other study involving investigational drugs, devices, or biologics.
• 24- Severe illness, other than heart disease, which would limit survival to a maximum of 1 year.
• 25- Peripheral vascular disease with rest pain or ischemic ulcers of the extremities.
• 26- Pregnancy.
• 27- Patient unwilling or unable to comply with study requirements.
• 28- Patients unable or unwilling to sign the written informed consent.
• 29- Technical obstacles, which pose an inordinately high surgical risk, in the judgment of the investigator.
• 30- Intolerance to anticoagulant or antiplatelet therapies or any other peri- or postoperative therapy that the investigator may administer based upon the patient's health status.
• 31- Specific liver enzymes [AST (SGOT) and ALT (SGPT)] 3 times upper limit of normal within 72 hours before implant.
• 32- Patient living alone (without an accompanying person).
• 33- Rapid AF, unless nodo-hissian junction ablation is considered.
• 34- Mid-septal end-systolic LV diameter ≤ 25mm
• 35- Sequential Organ Failure Assessment Score (SOFA score > 8)
• 36- Minor subjects, persons deprived of liberty, protected adults, or those unable to consent
• 37- Subjects who have participated in a clinical trial within 12 months
• 38- Patient implanted with an Implantable Cardioverter Defibrillator (ICD) other than Medtronic and Boston.