Efficacy of a device to narrow the coronary sinus in refractory angina

Abstract

Background: Many patients with coronary artery disease who are not candidates for revascularization have refractory angina despite standard medical therapy. The balloon-expandable, stainless steel, hourglass-shaped, coronary-sinus reducing device creates a focal narrowing and increases pressure in the coronary sinus, thus redistributing blood into ischemic myocardium.

Methods: We randomly assigned 104 patients with Canadian Cardiovascular Society (CCS) class III or IV angina (on a scale from I to IV, with higher classes indicating greater limitations on physical activity owing to angina) and myocardial ischemia, who were not candidates for revascularization, to implantation of the device (treatment group) or to a sham procedure (control group). The primary end point was the proportion of patients with an improvement of at least two CCS angina classes at 6 months.

Results: A total of 35% of the patients in the treatment group (18 of 52 patients), as compared with 15% of those in the control group (8 of 52), had an improvement of at least two CCS angina classes at 6 months (P=0.02). The device was also associated with improvement of at least one CCS angina class in 71% of the patients in the treatment group (37 of 52 patients), as compared with 42% of those in the control group (22 of 52) (P=0.003). Quality of life as assessed with the use of the Seattle Angina Questionnaire was significantly improved in the treatment group, as compared with the control group (improvement on a 100-point scale, 17.6 vs. 7.6 points; P=0.03). There were no significant between-group differences in improvement in exercise time or in the mean change in the wall-motion index as assessed by means of dobutamine echocardiography. At 6 months, 1 patient in the treatment group had had a myocardial infarction; in the control group, 1 patient had died and 3 had had a myocardial infarction.

Conclusions: In this small clinical trial, implantation of the coronary-sinus reducing device was associated with significant improvement in symptoms and quality of life in patients with refractory angina who were not candidates for revascularization. (Funded by Neovasc; COSIRA ClinicalTrials.gov number, NCT01205893.).

Figure 1

The Coronary Sinus Reducer System is comprised of the Reducer pre-mounted on the hour-glass shaped balloon catheter. After the Reducer is implanted in the coronary sinus, local flow disruption and vascular reaction leads to a hyperplastic response in the vessel wall, with occlusion of the fenestrations in the metal mesh. The central orifice of the Reducer remains patent and becomes the sole path for coronary sinus blood flow, resulting in a pressure gradient.

Figure 2

A: The proportion of patients improving by at least 2 CCS angina grades, and by at least 1 CCS angina grade, was significantly higher among Reducer patients compared to control (34.6% vs. 15.3% for at least 2 CCS angina grades, p=0.02; and 71.1% vs 42.3% for at least 1 CCS angina grade, p = 0.003). B: Mean CCS angina class was reduced from 3.19±0.4 at baseline to 2.13±0.97 at 6-month follow up in the Reducer group, and from 3.13±0.34 to 2.65±0.88 in the sham control group. The improvement was significantly better in the Reducer group (p=0.001).

Figure 3

The proportion of patients in each CCS class, by randomized group, at baseline and 6 months after randomization.

Figure 4

Cross sectional and longitudinal CT angiography views of the Reducer in the coronary sinus 6 months after implantation. The flow of contrast demonstrates continued patency of the device. The green and red bars in the longitudinal image, on the right, mark the positions of the cross-sectional images shown on the left. The red bars that appear in the third cross-sectional image and in the longitudinal image are in the same relative position in the two images and mark the positions of the opposing walls of the Reducer.