NHLBI SBIR/STTR Contract Topic

(Fast-Track proposals will be accepted.)

Number of anticipated awards: 1

Budget (total costs): Phase I: $200,000 for 12 months; Phase II: $1,500,000 for 2 years

It is strongly suggested that proposals adhere to the above budget amounts and project periods. Proposals with budgets exceeding the above amounts and project periods may not be funded.

Implanting large appliances, such as mitral valve replacement, currently requires cardiac surgery and cardiopulmonary bypass. Minithoracotomy access remains high risk. NHLBI has shown early feasibility of direct transthoracic large-port access to the beating heart, and effective closure using nitinol appliances in animal models. The objective of this contract solicitation is to support the commercial development of purpose-built access ports and closure devices for direct transthoracic cardiac access to the left and right ventricles.

Safe non-surgical access to the beating heart would be attractive to implant large appliances (such as mitral valve replacement), to repair complex congenital or structural heart defects, or to deliver smaller appliances such as transcatheter aortic valve replacement in the large minority of patients ineligible for transvascular delivery.

NHLBI DIR has demonstrated early feasibility of this approach using MRI guidance and off-the-shelf nitinol closure devices. A purpose-built device would be necessary for safe and robust transthoracic access port and closure.

A phase I award would develop and test a port and closure device system prototype. The awardee deliverable would be tested in vivo in the contracting DIR lab (cardiovascular intervention program).

The specific deliverables include:

• Access Port

• Access port in at least two sizes, one being 32Fr and another 24Fr, to accommodate implantation of large prostheses
• The port (Òintroducer sheathÓ) should incorporate features to assure retention inside the endocavitary space once delivered, to avoid inadvertent exit from the targeted ventricular cavity.
• The port should have a mechanism to protect against damage to endoventricular contents (papillary muscles, chordae tendinae, valve leaflets) during delivery.
• The system should have a hemostatic valve or equivalent mechanism to allow large appliances to be introduced into the heart from a transthoracic access port without significant blood loss and without entry of air.
• The system should feature sufficient taper, rigidity, and curvature to be introduced into the left or right ventricle via intercostal and subxiphoid trajectories, and characteristics to accomplish non-surgical intercostal separation if necessary.
• The system should allow delivery into the heart through the chest initially over a 0.035Ó guidewire
• The port should have length sufficient to reach the mid-left atrium or proximal ascending aorta from a transthoracic (subxiphoid and intercostal) access route in most patients.
• The system should be conspicuous under multiple imaging modalities, including ultrasound and MRI.
• The entire system should be MRI compatible (free from magnetic displacement and from significant magnetic susceptibility artifact) based on materials compatibility.
• The system should be curved to allow operation within a large-bore (70cm diameter) MRI system.

• Myocardial Closure System

• The myocardial port must be closed with high reliability, immediate hemostasis, and with a reliable bail-out mechanism in case of failure. Targeted clinical reliability will be successful deployment and immediate hemostasis in 99.9% of attempts.
• Anticipated closure mechanisms include permanent implants with suitable fixation mechanisms or suture-delivery. Any closure mechanism must assure high reliability of deployment, high reliability of success, robust immediate hemostasis, extremely low risk of late erosion or pseudoaneurysm, and trivial or no degradation of myocardial function.
• One minimal mechanism of bailout is a parallel guidewire that allows a bailout/temporizing hemostatic mechanism to be inserted quickly and reliably should hemostasis fail, to allow controlled surgical rescue. Other options are invited.
• The design should be safe from early and late myocardial erosion.
• The proposal should include a risk/failure analysis
• Operational considerations should be described, including whether the closure system is deployed at the beginning of the transcardiac procedure (Òpre-closeÓ) or at the conclusion.

• Strategies should be defined for use and withdrawal of secondary drainage catheters after the access port is closed.

A phase II award would allow mechanical, fatigue, and biocompatibility testing and regulatory development for the device to be used in human investigation, under Investigational Device Exemption. We expect the device will require a PMA for marketing, which is expensive. The contracting DIR lab would perform an IDE clinical trial at no cost to the awardee.

The specific Phase II deliverables are as described under Phase I.

• The phase II award would consist of the contractor obtaining an IDE based on the design finalized in phase I.