Overview: iCorNet Cardiac Support Net

Research background

Despite being treated with various treatments, patients suffering from heart failure is rapidly increasing all over the world. The medical cost has become a heavy social burden. There is an urgent need for development of new treatments that are inexpensive and widely adaptable.
Advanced heart failure exacerbates by progression of cardiac dilation (= cardiac remodeling).
Previously, a cardiac support treatment (Acorn CorCap) that covers a heart in a mesh-like bag has been developed to prevent cardiac remodeling and were used in Europe.
However, problems found; the size had to be adjusted during the operation, and the structure wrapping both ventricles evenly for sufficient pressure to the left ventricular surface causes a right ventricular diastolic failure and decreases cardiac output.

We have been entrusted with the "Problem-solving medical device development and improvement support project" by the Ministry of Economy, Trade and Industry for three years from 2011 and have been developing and researching a "tailor-made right ventricular restraint-reducing cardiac support net" to solve the above-mentioned problems in cardiac support treatment.

As results, we achieved followings.

• (1) Development of heart wall image extraction technology from heart MRI images of heart failure patients and established 3D heart model creation technology,
• (2) Development of a cardiac support net pattern creation program for a dedicated computer knitting machine,
• (3) Prototype of “Right ventricular restraint-reducing cardiac net” and shape optimization in chronic heart failure model,
• (4) Development of simulation technology that indicating the pressure distribution, wall stress, and wall displacement when the cardiac support net is implanted,
• (5) Development of simulation technology that indicates cardiac function when a cardiac net is attached, which covers both ventricle and pulmonary circulation / systemic circulation connection,
• (6) Experiments were conducted to evaluate the efficacy and safety of the "right ventricular restraint-reducing cardiac support net" in a large animal model of chronic heart failure,
• (7) We conducted a safety test based on GLP standards, and-
• (8) PMDA strategy consultations were conducted.

Furthermore, we prepared for multicenter Clinical research implementation and doctor-initiated clinical trials with the support of Translational Research Acceleration Network Seeds C by the Ministry of Education, Culture, Sports, Science and Technology from 2014 (by AMED from 2015).

Clinical research implementation background

This series of multicenter clinical study (FIH: First in Human) evaluates the safety of a tailor-made right ventricular restraint-relieving cardiac support net developed to prevent the progression of left ventricular remodeling in patients with dilated cardiomyopathy and has left ventricular dilatation.
The primary endpoint is to evaluate the safety of the test equipment, but the secondary endpoints are exploratory evaluation of effectiveness such as improvement of cardiac function, prevention of left ventricular remodeling, and improvement of QOL.

Patient selection criteria

1)　Target patients (target diseases)
Patients with dilated cardiomyopathy who present with heart failure and is not expected improvement in symptoms with the current treatment and who fall under III or IV in the NYHA classification (Excluding patients scheduled for combined surgery such as mitral valve replacement, mitral valve replacement, and tricuspid valve replacement).

2)　Selection criteria
Patients who meet all the following criteria are selected as subjects.

• ・ Patients who have voluntarily consented to participate in this study in writing.
• ・ Patients who are 20 years old or older and 75 years old or younger at the time of obtaining consent
• ・ Patients with persistent heart failure symptoms despite optimal drug treatment for heart failure for 3 months or longer, and no improvement in symptoms with current treatment (ACE inhibitors, ARBs, diuretics, beta-blockers, cardiotonic drugs, etc.)
• ・Patients fall under NYHA classification III or IV and patients fall under INTERMACS Profile Level 4-7
• ・ Patients with LVEDD ≥ 60 mm or LVED Di ≥ 30 mm /㎡ by echocardiography
• ・ Patients with LVEF ≤ 35% on echocardiography or RI examination
• ・ Patients with RVEDVi ≤ 170 mL /㎡ by MRI or CT examination
• ・ Patients who has a will to accept follow-up examinations and observations and can visit the medical institution.

3)　Exclusion criteria
Patients who fall under any of the following are excluded.

• ・ Patients with excessive cardiac enlargement (LVEDD> 85 mm).
• ・ Patients with severely impaired left ventricular function (LVEF <10%).
• ・ Patients having a history of cardiac surgery (this may not apply to patients with pericardial effusion and minor adhesion around the heart. ICD and pacemaker implantation surgery are excluded).
• ・ Patients scheduled for other cardiac surgery.
• ・ Patients with or will have CABG. ・ Patients who underwent PCI or trans-myocardial laser revascularization within 3 months before surgery or their candidates.
• ・ Patients undergoing IABP
• ・ Patients fall under NYHA classification IV and who are indicated for ventricular assist device and who wish to have a heart transplant.
• ・ Patients who have undergone biventricular paging (CRT (including ICD, pacemaker implantation surgery)) within 3 months before surgery or plan to have CRT in the future.
• ・ Patients with a life expectancy of less than 1 year, or patients with heart failure in the final stage of increased risk on surgery.

Research Method

• 1. Conduct the test on the target patients (3 patients) for whom consent was obtained at each joint research facility (5 universities). Create the tailor-made cardiac support net designed from data obtained from cardiac images and catheterization. Implantation surgery is performed under general anesthesia.
• 2. Evaluate cardiac function, remodeling effect, QOL, and exercise tolerance after 6 months, and evaluate adverse events and efficacy of treatment.
• 3. Nagoya University takes in charge of the clinical trial secretariat.