Device Evaluation

Humanitas University, Milan, Italy

Search for more papers by this author

Francesco Giannini

*Author for correspondence: Tel.: +39 333 753 5151;

E-mail Address: giannini_fra@yahoo.it

https://orcid.org/0000-0002-0517-1410

Interventional Cardiology Unit, GVM Care & Research Maria Cecilia Hospital, Via Madonna di Genova 1, Cotignola, RA, 48033, Italy

Search for more papers by this author

Published Online:27 Jun 2022https://doi.org/10.2217/fca-2021-0064

View article

Abstract

Refractory angina represents the final stage of chronic coronary artery disease, where anginal symptoms persist despite complete epicardial coronary artery revascularization and maximally tolerated pharmacological therapy. Percutaneous narrowing of the coronary sinus with the coronary sinus reducer (Reducer^®, Neovasc, Inc., Richmond, Canada) device was first attempted in humans in 2005 and has been shown to improve angina symptoms and the quality of life of patients suffering chronic refractory angina. It was recently included in the European guidelines for the management of chronic coronary syndrome and is progressively gaining popularity. The authors hereby provide a review of current literature on the topic, intending to facilitate insights and to promote further research on this device and its clinical applications.

Plain language summary

Coronary sinus reducer device implantation is a therapeutic option for patients suffering from chest tightness, discomfort and pain (collectively named angina when of clear cardiac origin), which persist for a long time despite optimal medical therapy and complete coronary revascularization. This is a novel device designed to be implanted, via a small puncture on the side of the neck, into the largest cardiac vein (i.e., the coronary sinus), to slow the outflow of blood from the cardiac venous system. Treatment is associated with significant improvement of symptoms in about 70–85% of patients, while granting little or no benefit in the remaining 15–30% for reasons that are yet to be determined. Importantly, the procedure has been shown to be safe and to have a very low rate of complications. Patients should keep this in mind when evaluating this therapeutic option.

Keywords:

Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1. Mannheimer C, Camici P, Chester MR et al. The problem of chronic refractory angina: report from the ESC Joint Study Group on the treatment of refractory angina. Eur. Heart J. 23(5), 355–370 (2002). • First international definition of refractory angina.
Medline CASGoogle Scholar
2. Knuuti J, Wijns W, Saraste A et al. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes – the task force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). Eur. Heart J. 41(3), 407–477 (2020). • Current guidelines of the European Society of Cardiology for the treatment of chronic coronary syndromes; these are the first guidelines to include coronary sinus reducer treatment as an option for refractory angina.
MedlineGoogle Scholar
3. Gallone G, Baldetti L, Tzanis G et al. Refractory angina. JACC Cardiovasc. Interv. 13(1), 1–19 (2020).
MedlineGoogle Scholar
4. Henry TD, Satran D, Jolicoeur EM. Treatment of refractory angina in patients not suitable for revascularization. Nat. Rev. Cardiol. 11(2), 78–95 (2014).
Medline CASGoogle Scholar
5. Henry TD, Satran D, Hodges JS et al. Long-term survival in patients with refractory angina. Eur. Heart J. 34(34), 2683–2688 (2013). •• Study on a large population with chronic refractory angina, as sampled from a dedicated refractory angina clinic, which first reported an overall survival on long-term that is comparable to the population with stable coronary artery disease and no refractory symptoms.
MedlineGoogle Scholar
6. Arora RR, Chou TM, Jain D et al. Effects of enhanced external counterpulsation on health-related quality of life continue 12 months after treatment: a substudy of the multicenter study of enhanced external counterpulsation. J. Investig. Med. 50(1), 25–32 (2002).
MedlineGoogle Scholar
7. Verheye S, Jolicoeur EM, Behan MW et al. Efficacy of a device to narrow the coronary sinus in refractory angina. N. Engl. J. Med. 372(6), 519–527 (2015). •• First randomized, sham-controlled trial evaluating coronary sinus reducer treatment.
Medline CASGoogle Scholar
8. Zipes DP, Svorkdal N, Berman D et al. Spinal cord stimulation therapy for patients with refractory angina who are not candidates for revascularization. Neuromodulation 15(6), 550–559 (2012).
MedlineGoogle Scholar
9. Beck CS, Leighninger DS. Scientific basis for the surgical treatment of coronary artery disease. JAMA 159(13), 1264–1271 (1955). • Surgical ligation of the coronary sinus for the treatment of angina; scientific basis for the ideation and development of the coronary sinus reducer device.
Medline CASGoogle Scholar
10. Beck CS, Leighninger DS. Operations for coronary artery disease. AMA Arch. Intern. Med. 97(5), 639–651 (1956).
Medline CASGoogle Scholar
11. Ido A, Hasebe N, Matsuhashi H, Kikuchi K. Coronary sinus occlusion enhances coronary collateral flow and reduces subendocardial ischemia. Am. J. Physiol. Heart Circ. Physiol. 280(3), H1361–H1367 (2001).
Medline CASGoogle Scholar
12. Banai S, Schwartz M, Sievert H, Seth A, Keren G, Parikh KH. Long-term follow-up to evaluate the safety of the Neovasc Reducer a device-based therapy for chronic refractory angina. J. Am. Coll. Cardiol. 55(10), A98.E927 (2010).
Google Scholar
13. Giannini F, Aurelio A, Jabbour RJ, Ferri L, Colombo A, Latib A. The coronary sinus reducer: clinical evidence and technical aspects. Expert Rev. Cardiovasc. Ther. 15(1), 47–58 (2017).
Medline CASGoogle Scholar
14. Konigstein M, Giannini F, Banai S, Giannini F. The reducer device in patients with angina pectoris: mechanisms, indications, and perspectives. Eur. Heart J. 39(11), 925–933 (2017).
Google Scholar
15. Banai S, Ben Muvhar S, Parikh KH et al. Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris. a prospective, open-label, multicenter, safety feasibility first-in-man study. J. Am. Coll. Cardiol. 49(17), 1783–1789 (2007).
MedlineGoogle Scholar
16. Giannini F, Palmisano A, Baldetti L et al. Patterns of regional myocardial perfusion following coronary sinus reducer implantation. Circ. Cardiovasc. Imaging 12(9), e009148 (2019). • First semi-quantitative analysis of ischemia at cardiac magnetic resonance following coronary sinus reducer placement.
MedlineGoogle Scholar
17. Campeau L. The Canadian Cardiovascular Society grading of angina pectoris revisited 30 years later. Can. J. Cardiol. 18(4), 371–379 (2002).
MedlineGoogle Scholar
18. Spertus JA, Winder JA, Dewhurst TA et al. Development and evaluation of the Seattle angina questionnaire: a new functional status measure for coronary artery disease. J. Am. Coll. Cardiol. 25(2), 333–341 (1995).
Medline CASGoogle Scholar
19. Enright PL, McBurnie MA, Bittner V et al. The 6-min walk test*: a quick measure of functional status in elderly adults. Chest 123(2), 387–398 (2003).
MedlineGoogle Scholar
20. Herdman M, Gudex C, Lloyd A et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual. Life Res. 20(10), 1727–1736 (2011).
Medline CASGoogle Scholar
21. Gallone G, Armeni P, Verheye S et al. Cost–effectiveness of the coronary sinus reducer and its impact on the healthcare burden of refractory angina patients. Eur. Heart J. Qual. Care Clin. Outcomes 6(1), 32–40 (2020).
MedlineGoogle Scholar
22. Abawi M, Nijhoff F, Stella PR et al. Safety and efficacy of a device to narrow the coronary sinus for the treatment of refractory angina: a single-centre real-world experience. Neth. Heart J. 24(9), 544–551 (2016).
Medline CASGoogle Scholar
23. Giannini F, Baldetti L, Ponticelli F et al. Coronary sinus reducer implantation for the treatment of chronic refractory angina: a single-center experience. JACC Cardiovasc. Interv. 11(8), 784–792 (2018).
MedlineGoogle Scholar
24. Ponticelli F, Tzanis G, Gallone G et al. Safety and efficacy of Coronary sinus reducer implantation at 2-year follow-up. Int. J. Cardiol. 292, 87–90 (2019).
MedlineGoogle Scholar
25. Konigstein M, Bazan S, Revivo M, Banai S. Coronary sinus reducer implantation improves symptoms, ischaemia and physical capacity in patients with refractory angina unsuitable for myocardial revascularisation: a single-centre experience. EuroIntervention 14(4), e452–e458 (2018).
MedlineGoogle Scholar
26. Giannini F, Baldetti L, Konigstein M et al. Safety and efficacy of the reducer: a multi-center clinical registry – REDUCE study. Int. J. Cardiol. 269, 40–44 (2018). • First and largest multicenter international observational registry of coronary sinus reducer patients.
MedlineGoogle Scholar
27. Verheye S, Agostoni P, Giannini F et al. Coronary sinus narrowing for the treatment of refractory angina: a multi-center prospective open-label clinical study (the REDUCER-I study). EuroIntervention 17(7), 561–568 (2020). • Single-arm, multicenter, observational study on coronary sinus reducer implantation.
Google Scholar
28. Tzanis G, Durante A, Mitomo S, Giannini F. Percutaneous management of periprocedural Coronary sinus reducer migration. Catheter. Cardiovasc. Interv. 93(4), e235–e237 (2019).
MedlineGoogle Scholar
29. Silvis MJM, Dekker M, Zivelonghi C et al. The Coronary Sinus Reducer; 5-year Dutch experience. Netherlands Heart J. 29(4), 215–223 (2021).
CASGoogle Scholar
30. D'Amico G, Giannini F, Massussi M et al. Usefulness of Coronary Sinus Reducer implantation for the treatment of chronic refractory angina pectoris. Am. J. Cardiol. 139, 22–27 (2021). • Multicenter observational study on coronary sinus reducer implantation.
MedlineGoogle Scholar
31. Zivelonghi C, Konigstein M, Azzano A et al. Coronary Sinus Reducer implantation results in improved oxygen kinetics at cardiopulmonary exercise test in patients with refractory angina. EuroIntervention 16(18), e1511–e1517 (2020).
Google Scholar
32. Parikh P, Bhatt P, Shah D et al. First-in-human use of Coronary Sinus Reducer in patients with refractory angina. J. Am. Coll. Cardiol. 72(24), 3227–3228 (2018).
MedlineGoogle Scholar
33. Konigstein M, Ponticelli F, Zivelonghi C et al. Long-term outcomes of patients undergoing Coronary Sinus Reducer implantation – a multicenter study. Clin. Cardiol. 44(3), 424–428 (2021). • Longest-term multicenter study on coronary sinus reducer implantation.
MedlineGoogle Scholar
34. Cullen JHS, Horsfield MA, Reek CR, Cherryman GR, Barnett DB, Samani NJ. A myocardial perfusion reserve index in humans using first-pass contrast-enhanced magnetic resonance imaging. J. Am. Coll. Cardiol. 33(5), 1386–1394 (1999).
Medline CASGoogle Scholar
35. Tzanis G, Palmisano A, Gallone G et al. The impact of the Coronary Sinus Reducer upon left ventricular function in patients with refractory angina pectoris. Catheter. Cardiovasc. Interv. 95(6), 1104–1108 (2019).
MedlineGoogle Scholar
36. Zivelonghi C, Verheye S, Timmers L et al. Efficacy of coronary sinus reducer in patients with non-revascularized chronic total occlusions. Am. J. Cardiol. 126, 1–7 (2020).
MedlineGoogle Scholar
37. Serruys PW. Assessing percutaneous intervention: re-appraising the significance of residual angina. EuroIntervention 10(11), 1253 (2015).
MedlineGoogle Scholar
38. Giannini F, Baldetti L, Ielasi A et al. First experience with the coronary sinus reducer system for the management of refractory angina in patients without obstructive coronary artery disease. JACC Cardiovasc. Interv. 10(18), 1901–1903 (2017).
MedlineGoogle Scholar
39. Zivelonghi C, Vermeersch G, Verheye S, Agostoni P. Incomplete coronary sinus reducer endothelialization as potential mechanism of clinical failure. Catheter. Cardiovasc. Interv. 94(1), 120–122 (2019).
MedlineGoogle Scholar
40. Giannini F, Tzanis G, Ponticelli F et al. Technical aspects in coronary sinus reducer implantation. EuroIntervention 15(14), 1269–1277 (2020).
MedlineGoogle Scholar
41. Tzanis G, Khokhar AA, Ponticelli F et al. Coronary sinus size and ischemia improvement after reducer implantation; “one size to fit them all?” Catheter. Cardiovasc. Interv. 98(3), e365–e369 (2021).
MedlineGoogle Scholar
42. Singhal S, Khoury S. Imaging of Thebesian venous system. N. Engl. J. Med. 359(7), e8 (2008).
Medline CASGoogle Scholar
43. Baldetti L, Colombo A, Banai S et al. Coronary sinus reducer non-responders: insights and perspectives. EuroIntervention 13(14), 1667–1669 (2018).
MedlineGoogle Scholar
44. Palmisano A, Giannini F, Rancoita P et al. Feature tracking and mapping analysis of myocardial response to improved perfusion reserve in patients with refractory angina treated by coronary sinus reducer implantation: a CMR study. Int. J. Cardiovasc. Imaging 37(1), 291–303 (2020). • Quantitative, feature-tracking analysis of ischemia at cardiac magnetic resonance acquisition on patients treated with the coronary sinus reducer.
MedlineGoogle Scholar
45. Akşit E, Barutçu A, Şehitoğlu MH et al. Association of abnormal coronary sinus reflux with coronary slow flow and importance of the Thebesian valve. Int. J. Cardiol. 319, 26–31 (2020).
MedlineGoogle Scholar
46. Akşit E, Altay S, Altun A. The importance of evaluating coronary sinus blood flow during the coronary sinus reducer treatment. Int. J. Cardiol. 336, 46 (2021).
MedlineGoogle Scholar

Vol. 18, No. 7

Supplemental Materials

Metrics

Downloaded 133 times

History

Received 10 May 2021

Accepted 17 May 2022

Published online 27 June 2022

Published in print July 2022

Information

Keywords

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fca-2021-0064

Financial & competing interests disclosure

F Giannini is a consultant for Neovasc, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

PDF download

Coronary sinus reducer for the treatment of chronic refractory angina pectoris

Abstract

Plain language summary

References