The Pressure-controlled Intermittent Coronary Sinus Occlusion on VentrIcular PERformance Study (PICSO-ViPER)

Understanding the Effects of Pressure-controlled Intermittent Coronary Sinus Occlusion Assisted Percutaneous Coronary Intervention on Coronary Physiology and Left Ventricular Performance

The PICSO ViPER study is a prospective single centre cohort study of the use of PICSO in patients presenting acute myocardial infarction and impaired function of the left ventricle and candidate to angioplasty the left anterior descending (LAD) coronary artery.

The percutaneous coronary intervention (PCI) procedure will be undertaken in a standard fashion, in accordance with the Oxford University Hospitals NHS Trust (OUHT) departmental guidelines for PCI, and includes the use of pressure wire measurements before and after stent deployment. PICSO treatment will be added on top of the conventional treatment.

The protocol will constitute of 5 main stages (that will all be performed during index angioplasty procedure). The protocol is complete at the end of the angioplasty procedure, and the patient will exit the study at this point. The five stages of the protocol are described below (for details see "Detailed Description"):

• Baseline
• PICSO treatment during pre-dilation
• Stenting with PICSO support
• Post-stent Physiology
• PICSO treatment during post-dilation

Study Overview

• Status: Terminated
• Conditions: Myocardial Infarction
• Intervention / Treatment: Device: PICSO

Detailed Description

In detail, the five stages of the PICSO VIPER study include:

Stage 1: Baseline

• Diagnostic angiography will be performed in the standard manner using appropriate catheters.
• Pre-stenting coronary physiology parameters, namely fractional flow reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) will be measured, using a pressure wire, as used for routine clinical measurements in patients undergoing PCI.
• Via a separate arterial access, a conductance catheter will be inserted retrogradely in the left ventricle for baseline measurements of cardiac pump function .
• Baseline blood samples will be withdrawn from the CS (via PICSO balloon) and ascending aorta (via coronary guiding catheter used for revascularization)

Stage 2: PICSO treatment during pre-dilation

• The PICSO device will be deployed as already previously described in the literature.
• Pre-dilation will be performed using an angioplasty balloon at a size determined by the operator, as per standard clinical practice. Balloon will be maintained inflated for a minimum of 1 minute to a maximum of 2 minutes if well tolerated by the patient.
• Balloon inflation will be performed once with the PICSO device activated and once with PICSO device in standby. The order of this will be determined by randomisation via Sequentially Numbered Opaque Sealed Envelopes.
• During each balloon inflation measurements of coronary and cardiac function will be performed and blood samples will be collected exactly as in stage 1.

Stage 3: Stenting with PICSO support

• Stenting is performed as usual clinical practice while the PICSO device is active. The overall duration of PICSO will be no less than 20 minutes, up to a maximum of 45 minutes.

Stage 4: Post-stent Physiology

• Post-stenting coronary and cardiac physiology parameters will be measured using a pressure wire and conductance catheter, respectively.
• Blood samples will be drawn from the CS and the coronary guide catheter as described in stage 1.

Stage 5

• Stent post-dilation will be performed using an angioplasty balloon at a size determined by the operator, as per standard clinical practice. Balloon will be maintained inflated for a minimum of 1 minute to a maximum of 2 minutes if well tolerated by the patient.
• Balloon inflation will be performed in all patients once with the PICSO device activated and once with the PICSO device in standby. The order of this will be the same as in Stage 2 (as determined by Sequentially Numbered Opaque Sealed Envelopes)
• During each balloon inflation measurements will be made of coronary and cardiac physiology parameters and blood samples will be drawn from the CS and the coronary guide catheter as described in stage 1.
• Following this, the participant completes and exits the study.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Giovanni Luigi De Maria, MD, PhD; Phone Number: 004401865226539; Email: giovanniluigi.demaria@ouh.nhs.uk
• Study Contact Backup: Name: Jubin Joseph, MD, PhD; Email: jubin.joseph@ouh.nhs.uk

Study Locations

• United Kingdom
  • Oxford, United Kingdom, OX39DU
    • Oxford Heart Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Admission with NSTEMI and considered for coronary angiogram for a view for PCI
• Echocardiographic evidence of at least mild left ventricular systolic impairment (Ejection Fraction < 50%) or regional wall motion abnormalities in LAD territory
• Angiographically proven stenosis of the LAD treated with PCI

Exclusion Criteria:

• Patient referred for surgical revascularization or considered for medical management of coronary disease
• Planned revascularization by mean of balloon angioplasty without stenting

• Patients in whom safety or clinical concerns preclude participation. These would include:

  • Significant left main stem disease
  • Cardiogenic shock and/or haemodynamic instability at the time of enrolment/screening
• Recent PCI or admission with acute coronary syndrome in the previous 3 months before screening/enrolment
• Known anaemia (Hb < 90 g/L)
• Pregnant or breast-feeding females
• History of stroke, TIA or reversible ischaemic neurological disease within last 6 months
• Known severe renal failure (eGFR < 30 ml/min/1.73m2) or history of dialysis or renal transplant
• Previous coronary bypass artery grafting
• Previous PCI to LAD
• Known severe valvular abnormalities
• Use of warfarin
• Presence of pacemaker electrode or medical device in the coronary sinus
• History of inability or, in the opinion of the investigator, anticipated inability to tolerate pharmacologic stress testing (e.g. second- or third-degree AV block without a cardiac pacemaker, severe asthma, resting systolic blood pressure <90mmHg, unstable coronary disease, use of medications which may interfere with the test).
• Unwilling, or unable, to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: PICSO therapy Group; This will be the only treatment of the PICSO VIPER study. Within this group patients will be randomised to have cycles of 2 minutes of balloon-induced myocardial schema with PICSO device in "ON" vs "OFF" modality.

Device: PICSO; PICSO therapy is delivered through the PICSO Impulse System, which consists of the PICSO Impulse console and PICSO impulse catheter. The PICSO therapy is delivered in each patient for a minimum of 20 minutes to a maximum of 45 minutes. The PICSO Impulse catheter is automatically activated by the PICSO Impulse console. It is inserted in the coronary sinus via femoral vein access. The PICSO Impulse Console cyclically inflates and deflates the balloon at the tip of the PICSO Impulse catheter, generating transient increase in coronary sinus pressure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
End-systolic pressure volume relationship (ESPVR)	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
End diastolic pressure volume relationship (EDPVR)	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Minimum dp/dt	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Maximum dp/dt	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Tau	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Stroke work	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Pressure-Volume Area (PVA)	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Cardiac Efficiency	Parameter of ventricular physiology and performance	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcoronary gradient of lactates levels	Cardiac metabolism and energetics	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Transcoronary oxygen content	Cardiac metabolism and energetics	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Transcoronary microRNA gradient	Cardiac metabolism and energetics	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurement of IMR	Coronary microvascular function	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Measurement of CFR	Coronary microvascular function	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Measurement of Coronary wedge pressure during balloon occlusion.	Coronary microvascular function	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Time for PICSO deployment	Safety Endpoint rate of coronary sinus complications: perforation, dissection, thrombosis; time for PICSO deployment / screening time and radiation dose	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Screening time for PICSO deployment	Safety Endpoint rate of coronary sinus complications: perforation, dissection, thrombosis; time for PICSO deployment / screening time and radiation dose	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Radiation dose for PICSO deployment	Safety Endpoint	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Rate of coronary sinus perforation	Safety Endpoint	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Rate of coronary sinus dissection	Safety Endpoint	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Rate of coronary sinus thrombosis	Safety Endpoint	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)
Rate of PICSO failure deployment	Safety Endpoint	At completion of index percutaneous coronary intervention (on average 90 minutes post enrolment)

Collaborators and Investigators

• Sponsor: Oxford University Hospitals NHS Trust
• Collaborators: Miracor Medical SA
• Investigators: Study Chair: Giovanni Luigi De Maria, MD, PhD, Oxford University Hospitals - NHS Foudation Trust

Publications and helpful links

General Publications

• Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Juni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO; ESC Scientific Document Group. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2019 Jan 7;40(2):87-165. doi: 10.1093/eurheartj/ehy394. No abstract available. Erratum In: Eur Heart J. 2019 Oct 1;40(37):3096.
• Kirtane AJ, Moses JW. Revascularization in heart failure: the role of percutaneous coronary intervention. Heart Fail Clin. 2007 Apr;3(2):229-35. doi: 10.1016/j.hfc.2007.05.003.
• Martinez GJ, Yong AS, Fearon WF, Ng MK. The index of microcirculatory resistance in the physiologic assessment of the coronary microcirculation. Coron Artery Dis. 2015 Aug;26 Suppl 1:e15-26. doi: 10.1097/MCA.0000000000000213.
• Lazar HL, Rajaii A, Roberts AJ. Reversal of reperfusion injury after ischemic arrest with pressure-controlled intermittent coronary sinus occlusion. J Thorac Cardiovasc Surg. 1988 Apr;95(4):637-42.
• Spaan JA. Mechanical determinants of myocardial perfusion. Basic Res Cardiol. 1995 Mar-Apr;90(2):89-102. doi: 10.1007/BF00789439. No abstract available.
• Duncker DJ, Bache RJ. Regulation of coronary blood flow during exercise. Physiol Rev. 2008 Jul;88(3):1009-86. doi: 10.1152/physrev.00045.2006.
• Lazar HL. Advantages of pressure-controlled intermittent coronary sinus occlusion over left ventricle-powered coronary sinus retroperfusion. Ann Thorac Surg. 2001 Jan;71(1):402. doi: 10.1016/s0003-4975(00)02036-1. No abstract available.
• Martin JS, Byrne JG, Ghez OY, Sayeed-Shah U, Grachev SD, Laurence RG, Cohn LH. LV-powered coronary sinus retroperfusion reduces infarct size in acutely ischemic pigs. Ann Thorac Surg. 2000 Jan;69(1):84-9. doi: 10.1016/s0003-4975(99)00865-6.
• 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. 2001 Mar;280(3):H1361-7. doi: 10.1152/ajpheart.2001.280.3.H1361.
• Mohl W, Mina S, Milasinovic D, Kasahara H, Wei S, Maurer G. Is activation of coronary venous cells the key to cardiac regeneration? Nat Clin Pract Cardiovasc Med. 2008 Sep;5(9):528-30. doi: 10.1038/ncpcardio1298. No abstract available.
• Van de Hoef TP, Nolte F, Delewi R, Henriques JP, Spaan JA, Tijssen JG, Siebes M, Wykrzykowska JJ, Stone GW, Piek JJ. Intracoronary hemodynamic effects of pressure-controlled intermittent coronary sinus occlusion (PICSO): results from the First-In-Man Prepare PICSO Study. J Interv Cardiol. 2012 Dec;25(6):549-56. doi: 10.1111/j.1540-8183.2012.00768.x. Epub 2012 Sep 20.
• van de Hoef TP, Nijveldt R, van der Ent M, Neunteufl T, Meuwissen M, Khattab A, Berger R, Kuijt WJ, Wykrzykowska J, Tijssen JG, van Rossum AC, Stone GW, Piek JJ. Pressure-controlled intermittent coronary sinus occlusion (PICSO) in acute ST-segment elevation myocardial infarction: results of the Prepare RAMSES safety and feasibility study. EuroIntervention. 2015 May;11(1):37-44. doi: 10.4244/EIJY15M03_10.
• De Maria GL, Alkhalil M, Borlotti A, Wolfrum M, Gaughran L, Dall'Armellina E, Langrish JP, Lucking AJ, Choudhury RP, Kharbanda RK, Channon KM, Banning AP. Index of microcirculatory resistance-guided therapy with pressure-controlled intermittent coronary sinus occlusion improves coronary microvascular function and reduces infarct size in patients with ST-elevation myocardial infarction: the Oxford Acute Myocardial Infarction - Pressure-controlled Intermittent Coronary Sinus Occlusion study (OxAMI-PICSO study). EuroIntervention. 2018 Jun 8;14(3):e352-e359. doi: 10.4244/EIJ-D-18-00378.

Study record dates

Study Major Dates

• Study Start (Actual): August 3, 2021
• Primary Completion (Actual): December 29, 2022
• Study Completion (Actual): December 29, 2022

Study Registration Dates

• First Submitted: June 3, 2019
• First Submitted That Met QC Criteria: July 24, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction
• Other Study ID Numbers: 14338

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No