Coronary Sinus Reducer Objective Impact on Symptoms, MRI Ischemia and Microvascular Resistance - ORBITA-COSMIC

Apr 08, 2024
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
Medical Research Council, Imperial College Healthcare Charity, National Institute for Health and Care Research Imperial Biomedical Research Centre, St Mary’s Coronary Flow Trust, British Heart Foundation
Date Presented:
04/08/2024
Date Published:
04/08/2024
Original Posted Date:
04/08/2024
References

Contribution To Literature:

In patients with refractory angina without revascularization options in the ORBITA-COSMIC trial, CSR implantation was associated with decreased angina frequency compared with a sham control, potentially by improving subendocardial perfusion in ischemic myocardium.

Description:

The goal of the trial was to determine the effects of a coronary sinus reducer (CSR) device versus sham control on both myocardial blood flow (MBF) assessed by stress perfusion cardiac magnetic resonance imaging (CMR) and daily angina burden in patients with refractory angina.

Study Design

  • Randomized
  • Double-blind
  • Placebo-controlled
  • Multicenter

Patients with stable angina on maximal antianginal therapy without options for revascularization were randomized in a 1:1 fashion to Neovasc Reducer System CSR implantation (n = 25) or sham control (n = 26). Patients donned headphones playing music for auditory blinding. Internal jugular vein cannulation, right atrial catheterization, and coronary sinus venogram were performed and deep sedation initiated prior to randomization. The treatment arm underwent standard CSR implantation, while the sham arm remained sedated on the procedure table for at least 15 minutes to approximate the duration of CSR implantation.

  • Total number of enrollees: 51
  • Duration of follow-up: 6 months
  • Median patient age: 67 years
  • Percentage female: 14%

Inclusion criteria:

  • Age ≥18 years
  • Myocardial ischemia on stress perfusion CMR
  • Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated antianginal therapy
  • Stable coronary artery disease (CAD) not amenable for revascularization

Exclusion criteria:

  • Acute coronary syndrome <3 months prior
  • Coronary revascularization <6 months prior
  • Right atrial or ventricular intracardiac pacemaker or defibrillator leads
  • Left ventricular ejection fraction (LVEF) <25%
  • Right atrial pressure ≥15 mm Hg
  • Estimated glomerular filtration rate <15 mL/min/1.73 m2
  • Contraindication to CMR or adenosine

Other salient features/characteristics:

  • Previous coronary artery bypass grafting (CABG): 86%
  • Previous percutaneous coronary intervention (PCI): 55%
  • Median antianginal medications: 3
  • CCS class III-IV angina: 94%
  • LVEF <55%: 18%

Principal Findings:

The primary imaging outcome, difference between CSR vs. sham 6-month change from baseline adenosine-stress MBF in nontransmurally infarcted, ischemic wall segments, was: +0.06 mL/min/g (95% credible interval [CrI] -0.09 to +0.20), probability of benefit (Pr[Benefit]) = 78.8%.

The primary symptom outcome, odds of fewer daily angina episodes at 6 months, for CSR vs. sham, was: odds ratio 1.40 (95% CrI 1.08-1.83), Pr(Benefit) = 99.4%

Secondary imaging outcomes, difference between CSR vs. sham 6-month change from baseline:

  • Endocardial:epicardial stress MBF ratio, ischemic segments: +0.09 (95% CrI 0.00 to +0.17), Pr(Benefit) = 98.2%
  • Endocardial:epicardial stress MBF ratio, nonischemic segments: -0.02 (95% CrI -0.10 to +0.07), Pr(Benefit) = 35.1%

Secondary symptom outcomes for CSR vs. sham, change from baseline at 6 months:

  • Seattle Angina Questionnaire (SAQ) angina frequency: +22.7 (95% CrI +10.6 to 34.6) vs. +6.5 (95% CI -3.5 to +16.6), Pr(Benefit) = 99.7%
  • MacNew Heart Disease Health-Related Quality of Life: +0.5 (95% CrI 0.0 to +1.0) vs. -0.1 (95% CrI -0.6 to +0.3), Pr(Benefit) = 99.4%

Safety outcomes:

  • All-cause death, myocardial infarction, stroke, or hemorrhage in entire cohort: 0%
  • CSR device embolization: 8%

Interpretation:

In patients with refractory angina, the small proof-of-concept ORBITA-COSMIC trial demonstrated that CSR implantation was associated with significant reduction in daily angina burden and heart disease-related quality of life. Study participants had been exhaustively optimized pre-randomization both medically and via revascularization, with many having undergone both CABG and PCI. Compared to the near-immediate therapeutic benefit observed post-PCI in ORBITA-2, the antianginal effect of CSR took about 10 weeks to manifest based on patient-reported symptoms. The mechanism of this effect is not entirely clear.

The trial’s secondary outcome of increased stress MBF to ischemic myocardium, though based on prior animal data, was neutral. Secondary analysis suggested that increased perfusion within these segments to the most vulnerable subendocardial layer may have contributed, though this remains exploratory. Nevertheless, the observed improvements in patient-reported angina burden and quality of life suggest that CSR may be a reasonable modality in patients with advanced and debilitating CAD – this concept needs further study.

References:

Foley MJ, Rajkumar CA, Ahmed-Jushuf F, et al. Coronary sinus reducer for the treatment of refractory angina (ORBITA-COSMIC): a randomized, placebo-controlled trial. Lancet 2024;Apr 8:[Epub ahead of print].

Presented by Dr. Michael Foley at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 8, 2024.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease

Keywords: ACC24, ACC Annual Scientific Session, Myocardial Ischemia


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