Intramural drug delivery by direct injection within the arterial wall: first clinical experience with a novel intracoronary delivery-infiltrator system.

ABSTRACT

Local drug delivery at the lesion site in patients with coronary artery disease is being intensively studied to prevent restenosis after percutaneous coronary intervention. However, the effective penetration of the delivered agents into the vessel wall and delivery time remain considerable problems for all currently existing devices. A unique, new catheter has been invented, the infiltrator Angioplasty Balloon Catheter (IABC), which has the capability to allow intramural drug delivery by direct injection within the arterial wall. We describe the first clinical experience with this catheter. IABC is an angioplasty catheter with 3 lumens one for inflating the balloon, one central for the guidewire, and a third for drug delivery. On the surface of the balloon there are 3 longitudinal strips of 6 injection needles, which on inflation stand 0.01" high, and are connected to the drug-delivery lumen. With inflation of the balloon, the needles penetrate the lesion, allowing drug delivery into the media of the vessel wall. We used the IABC in 17 patients (age = 58 +/- 9 years) undergoing coronary angioplasty. All patients were symptomatic, with significant lesions (13 LAD, 3 LCX, 1 RCA) and documented ischemia. Following initial dilatation with a conventional angioplasty balloon (stenosis from 72 +/- 8% to 26 +/- 14%, P < 0.001), the IABC was used to infiltrate the lesion with 0.4 ml (6,000 IU) of low-molecular-weight heparin (Fraxiparine). For the delivery, the IABC was inflated to 1-2 atm for 30-45 s, and the heparin was injected by hand in 5 s. Lesion residual stenosis and morphology remained unchanged after IABC use (26 +/- 14% to 22 +/- 11%, P = NS). In 10 patients, stent placement followed the IABC use. The decision to proceed with stent placement was made after the initial dilatation with the conventional balloon, and it was not influenced by the IABC use. Stent placement greatly improved the final result (for the whole patient group 22 +/- 11% to 5 +/- 18%, for the stented patients 22 +/- 13% to -7 +/- 10%, P < 0.001 for both). Hospital course was uneventful, with no electrocardiogram changes and normal cardiac enzymes for all patients. We have shown that the use of a unique new catheter (IABC) for intramural drug delivery in human patients undergoing coronary angioplasty is feasible and safe. This catheter is the first of a new generation of catheters and represents a significant step in local drug delivery. It is very promising as a vehicle to modify plaque behavior and potentially influence restenosis after angioplasty.