RESCUE-HF Trial: Retrograde Delivery of Allogeneic Umbilical Cord Lining Subepithelial Cells in Patients with Heart Failure

Abstract

Cell therapy is an evolving option for patients with end-stage heart failure. First-generation cell therapy trials have had marginal success. Our goal was to evaluate retrograde delivery of allogeneic umbilical cord subepithelial cells (UCSECs) in patients with heart failure. A prospective open-label dose escalation study of the safety and feasibility of UCSECs infused retrogradely into the coronary sinus was performed. Patients received a single dose of either 100 million (M), 200M, or 400M cells. The patients were followed for 2 years. Twenty-four patients were successfully enrolled in the study. The patients had UCSEC infusion without procedure-related complications. The ejection fraction in patients receiving UCSECs demonstrated improvement compared to baseline; from 25.4% (±5.5) at screening to 34.9% (±4.1) at 12 months. End-systolic diameter decreased significantly from 59.9 (±5.3) mm to 52.6 (±2.7) mm (p < 0.05). Retrograde UCSEC delivery was safe and feasible in all three dosage groups. Patients receiving 200M and 400M UCSECs showed signs of early improvement in left ventricular ejection fraction (LVEF) and remodeling. This study provides the basis for a larger clinical trial in heart failure (HF) patients using the middle or high dose of UCSECs.

Catheter‐based retrograde coronary sinus infusion is a practical delivery technique for introducing biological molecules into the cardiac system

“…Several clinical studies have been published that examined the safety and efficacy of retrograde infusion therapies. The retrograde delivery techniques employed in these studies included (a) fixed infusion volume and fixed plasmid concentration, (b) fixed infusion volume with variable plasmid concentration, and (c) variable infusion volume with fixed plasmid concentration . However, none of these studies included a characterization of the global cardiac distribution of the biological molecules after infusion.…”

“…The secondary objective of this study was to evaluate the Advance® CS Coronary Sinus Infusion Catheter . The Advance® CS Coronary Sinus Infusion Catheter was used in the REVIVE and RESCUE‐HF human clinical trials, wherein autologous bone marrow cell concentrate and allogeneic umbilical cord sub‐epithelial cells, respectively, were successfully delivered via a retrograde approach through the CS. The catheter has 510(k) clearance and CE mark for “temporary occlusion of the coronary sinus for delivery of contrast media, drugs, therapeutic agents, or for possible introduction of devices into the coronary venous system.” The catheter is currently available in shaft lengths of 80 and 135 cm.…”

“…Preclinical testing has shown that the CS could be occluded for up to 1 hr without detrimental effects . In general, the high volume capacity and low pressure environment of the coronary venous system are features conducive to retrograde infusion therapies, as demonstrated in recent human clinical studies …”

“…6 In general, the high volume capacity and low pressure environment of the coronary venous system are features conducive to retrograde infusion therapies, as demonstrated in recent human clinical studies. [6][7][8][9] The primary objective of this study was to characterize in a porcine model the cardiac biodistribution and functional protein expression of luciferase plasmid 24-hr after catheter-based balloon occlusion of the CS and retrograde infusion into the cardiac venous system. The secondary objective of the study was to assess the safety and efficacy of the Advance ® CS Coronary Sinus Infusion Catheter (Cook Medical, Bloomington, IN) as a device for introducing biological molecules into the cardiac venous network via a retrograde approach through the CS.…”

Cell therapy for dilated cardiomyopathy: State-of-the-art

“…), а также достоверно уменьшился КДР ЛЖ (с 59,9±5,3 мм до 52,6±2,7 мм); р<0,05. Одновременно была продемонстрирована безопасность ретроградного введения пуповинных клеток в коронарный синус [45].…”