Newly published findings reveal that the coronary sinus (CS) reducer (Neovasc/Shockwave Medical) significantly reduces angina symptoms and improves quality of life for patients with coronary microvascular dysfunction (CMD). Writing in the journal JACC Cardiovascular Interventions, the research team believes the device may emerge as a novel therapy for patients with angina with no obstructive coronary artery disease (ANOCA), where current effective treatment options are limited. “[The current study] suggests a mechanism of action related to overall function of the microcirculation rather than mediated by a specific effect on the endothelium,” said the authors of the paper, led by David Tryon, MD, from the Mayo Clinic based in Rochester, Minnesota. Main findings Findings from the NeoVasc/Shockwave Medical-supported study revealed in patients with low baseline coronary flow reserve (CFR) (endothelium independent CMD), CFR increased significantly from 2.1 (1.95-2.30) to 2.7 (2.45-2.95) (n=19; P=0.0011). Patients with abnormal coronary blood flow (CBF) response to acetylcholine at baseline (endothelium-dependent CMD) had an increase in CBF response to acetylcholine: -11.0% (-20.15% to 5.85%) to 11.5% (-4.82% to 39.29%) (n=11; P=0.042). There was a significant improvement in Canadian Cardiovascular Society (CCS) angina class from 4.0 (3.25-4.0) to 2.0 (2.0-3.0) (P < 0.001) and increase in each domain of the Seattle Angina Questionnaire (SAQ) questionnaire (P<0.006 for all). “Combining all 30 study participants, CFR increased significantly from baseline to 120-day follow-up, suggesting improvement in CFR regardless of the mechanism of CMD,” said the paper’s authors. CMD subtypes In accompanying editorial commentary, Tim P. van de Hoef, MD, PHD from University Medical Center Utrecht in the Netherlands homed in on the efficacy of CS reducer therapy across all CMD subtypes, including endothelium-dependent CMD. He went on to stress its importance particularly as patients with this CMD subtype were not routinely identified during contemporary coronary function testing. “Currently, assessment of endothelium-dependent microvascular function during coronary vasomotor testing relies on beat-to-beat changes in coronary flow using intracoronary Doppler flow velocity measurements,” said Dr. van de Hoef. “However, these measurements are not routinely performed, as the intracoronary Doppler system is currently not clinically available. As a result, this form of CMD goes undetected in clinical practice.” Dr. van de Hoef added that these patients, which responded to coronary sinus reducer implantation both hemodynamically and symptomatically, highlighted the need to incorporate endothelial function assessment in routine evaluation of ANOCA patients. CFR threshold The editorial also highlighted the study’s use of a CFR threshold of 2.5 to diagnose CMD, higher than in previous ANOCA studies but consistent with recent pathophysiological studies. “The finding that coronary sinus reducer implantation improves both coronary hemodynamics and angina symptoms in patients selected using this threshold supports its adoption in clinical practice and research,” said Dr van de Hoef. “This is significant because it suggests that patients previously considered to have normal coronary hemodynamics based on lower CFR thresholds may deserve reconsideration of their clinical situation.” A limitation saw the research team use an adenosine dose to induce coronary hyperemia limited to 72mg, whereas dose-response studies suggest that 200mg is required to reach maximal coronary flow velocity in the left coronary artery. “This raises the question of whether all enrolled patients truly had CMD or if some would have crossed the 2.5 CFR threshold with higher-dose adenosine,” said Dr van de Hoef. “Although most patients responded to coronary sinus reducer therapy, these considerations may explain why some patients did not benefit from the device.” Study approach This Phase II trial enrolled 30 patients with ANOCA, invasively diagnosed CMD, and Canadian Cardiovascular Society (CCS) class 3 to 4 angina despite medical therapy. These patients had a mean age of 54.8±11.0 years; 67% (20/30) were women. CMD was defined by coronary flow reserve (CFR) ≤2.5 and/or ≤50% increase in coronary blood flow (CBF) in response to intracoronary infusion of acetylcholine. Invasive coronary microvascular function testing was performed before and at 120 days post-implantation. The primary endpoint was change in microvascular function at 120 days. Sources: Tryon D, Corban MT, Alkhouli M, et al. Coronary Sinus Reducer Improves Angina, Quality of Life, and Coronary Flow Reserve in Microvascular Dysfunction. JACC Cardiovasc Interv. 2024 Nov 6. [Article in Press]. van de Hoef TP. The Coronary Sinus Reducer as a Game-Changer for the Treatment of Coronary Microvascular Dysfunction. JACC Cardiovasc Interv. 2024 Nov 6. [Article in Press]. Image Credit: Gajus - stock.adobe.com