Clinical trial NCT04121845: CoROnary SinuS Reducer implantatiOn for ischemiA reDuction
Official title: The Influence of Coronary Sinus Reducer Implantation on Exertional Capacity, Extent of Myocardial Ischemia and hrECG Markers of Arrhythmogenicity in Patients With Refractory Angina Pectoris
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Refractory Angina Pectoris
Keywords: angina pectoris
coronary sinus reducer
quality of life
reversible ischemia
exercise testing
oxygen consumption
Lead sponsor: University Medical Centre Ljubljana
Sponsor class: OTHER
First posted: 2019-10-10
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with refractory angina pectoris have low quality of life and reduced exertional capacity. Studies have shown that the coronary sinus reducer (CSR) implantation improves the quality of life. However, to date there are no firm objective data on improvement of exertional capacity. Studies have shown a large influence of placebo effect after interventional procedures, which is even more pronounced than in medically treated patients. As angina pectoris presents entirely subjective perception of chest discomfort, its improvement may be influenced by this effect in up to 30 %. The investigators will study weather the CSR implantation improves aerobic exertional capacity in comparison to optimal medical therapy alone. Further, the investigators will explore the extent of myocardial reversible ischemia reduction and possible influence on hrECG markers of left ventricular arrhythmogenicity. 40 patients with refractory angina CCS class (Canadian cardiovascular society) II-IV and confirmed reversible ischemia will be included. Patients will be randomized into two groups. The first group will undergo CSR implantation procedure. The second group will present a sham control group with placebo procedure. At inclusion and after 6 months the investigators will perform cardiopulmonary exercise test (CPET), single photon emission tomography for detection of reversible ischemia (SPECT), high resolution ECG (hrECG), echocardiography and asses the subjective burden of angina according to CCS score and the quality of life according to the Seattle angina Questionnaire (SAQ).


Eligibility criteria: Inclusion Criteria:

* angina pectoris CCS class II-IV
* receiving optimal medical therapy for at least one month
* confirmed reversible myocardial ischemia in left anterior descending coronary artery (LAD) and/or left circumflex coronary artery (LCX) territory by SPECT
* not candidate for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)

Exclusion Criteria:

* recent non stable angina pectoris (within 1 months)
* recent acute coronary syndrome (within 3 months)
* recent successful PCI and/or CABG (within 6 months)
* decompensated heart failure and/or recent (within 3 months) hospitalization due to heart failure
* severe heart valve(s) disease
* advanced chronic obstructive pulmonary disease (COPD) or poorly managed asthma
* peripheral arterial disease, musculoskeletal disorder or central nervous system disease which preclude exercise testing

Primary outcomes:
measure: Impact of CSR versus placebo procedure on exertional capacity measured by maximal oxygen consumption (VO2) during cardio-pulmonary exercise testing.
timeFrame: 6 months
Secondary outcomes:
measure: Impact of CSR versus placebo procedure on exercise duration time during cardio-pulmonary exercise testing.
timeFrame: 6 months
measure: Change in the extent of myocardial reversible ischemia calculated by single-photon emission computed tomography (dynamic scintigraphy).
timeFrame: 6 months
measure: Change in the extent of myocardial reversible ischemia calculated by single-photon emission computed tomography (static scintigraphy).
timeFrame: 6 months
measure: Change in RR interval variability as assessed by hrECG.
timeFrame: 6 months
measure: Change in late potentials as assessed by hrECG.
timeFrame: 6 months
measure: Change in QT variability as assessed by hrECG.
timeFrame: 6 months
measure: Change in Canadian Cardiovascular Society angina pectoris class (CCS).
timeFrame: 3 months, 6 months
measure: Impact of CSR versus placebo procedure on quality of life according to Seattle angina questionnaire (SAQ).
timeFrame: 3 months, 6 months
Other outcomes:
measure: Influence of CSR implantation on echocardiographically assessed left ventricular elastance.
timeFrame: 6 months
measure: Influence of CSR implantation on diastolic strain.
timeFrame: 6 months
Locations:
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
Study officials:
affiliation: University Medical Centre Ljubljana, Slovenia
name: Matjaž Bunc, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Centre Ljubljana, Slovenia
name: David Žižek, Assoc. Prof.
role: STUDY_CHAIR
References:
citation: Mannheimer C, Camici P, Chester MR, Collins A, DeJongste M, Eliasson T, Follath F, Hellemans I, Herlitz J, Luscher T, Pasic M, Thelle D. The problem of chronic refractory angina; report from the ESC Joint Study Group on the Treatment of Refractory Angina. Eur Heart J. 2002 Mar;23(5):355-70. doi: 10.1053/euhj.2001.2706. No abstract available.
citation: Henry TD, Satran D, Hodges JS, Johnson RK, Poulose AK, Campbell AR, Garberich RF, Bart BA, Olson RE, Boisjolie CR, Harvey KL, Arndt TL, Traverse JH. Long-term survival in patients with refractory angina. Eur Heart J. 2013 Sep;34(34):2683-8. doi: 10.1093/eurheartj/eht165. Epub 2013 May 12.
citation: 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. 2017 Jan;15(1):47-58. doi: 10.1080/14779072.2017.1270755.
citation: Konigstein M, Verheye S, Jolicoeur EM, Banai S. Narrowing of the Coronary Sinus: A Device-Based Therapy for Persistent Angina Pectoris. Cardiol Rev. 2016 Sep-Oct;24(5):238-43. doi: 10.1097/CRD.0000000000000101.
citation: Verheye S, Jolicoeur EM, Behan MW, Pettersson T, Sainsbury P, Hill J, Vrolix M, Agostoni P, Engstrom T, Labinaz M, de Silva R, Schwartz M, Meyten N, Uren NG, Doucet S, Tanguay JF, Lindsay S, Henry TD, White CJ, Edelman ER, Banai S. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med. 2015 Feb 5;372(6):519-27. doi: 10.1056/NEJMoa1402556.
citation: Konigstein M, Meyten N, Verheye S, Schwartz M, Banai S. Transcatheter treatment for refractory angina with the Coronary Sinus Reducer. EuroIntervention. 2014 Feb;9(10):1158-64. doi: 10.4244/EIJV9I10A196.
citation: Abawi M, Nijhoff F, Stella PR, Voskuil M, Benedetto D, Doevendans PA, Agostoni P. 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. 2016 Sep;24(9):544-51. doi: 10.1007/s12471-016-0862-2.
citation: Banai S, Ben Muvhar S, Parikh KH, Medina A, Sievert H, Seth A, Tsehori J, Paz Y, Sheinfeld A, Keren G. 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. 2007 May 1;49(17):1783-9. doi: 10.1016/j.jacc.2007.01.061.
citation: Myers J, Froelicher VF. Optimizing the exercise test for pharmacological investigations. Circulation. 1990 Nov;82(5):1839-46. doi: 10.1161/01.cir.82.5.1839.
citation: Kralios AC, Nappi JM, Tsagaris TJ, Kralios FA, Kuida H. Paradoxical increase of ventricular fibrillation threshold in response to coronary sinus obstruction. Am Heart J. 1988 Feb;115(2):334-40. doi: 10.1016/0002-8703(88)90479-6.
citation: Kralios AC, Anderson FL, Kralios FA. Protective effect of coronary sinus obstruction from primary ischemia-induced ventricular fibrillation in the dog. Am Heart J. 1993 Apr;125(4):987-95. doi: 10.1016/0002-8703(93)90105-i.
citation: De Maria GL, Kassimis G, Raina T, Banning AP. Reconsidering the back door approach by targeting the coronary sinus in ischaemic heart disease. Heart. 2016 Aug 15;102(16):1263-9. doi: 10.1136/heartjnl-2016-309642. Epub 2016 Jun 10.
citation: Baldetti L, Colombo A, Banai S, Latib A, Esposito A, Palmisano A, Giannini F. Coronary sinus Reducer non-responders: insights and perspectives. EuroIntervention. 2018 Feb 20;13(14):1667-1669. doi: 10.4244/EIJ-D-17-00626.